Ischemic Stroke, Brain Attack

Introduction:

According to the World Health Organization, both stroke and coronary heart disease are types of cardiovascular diseases. Brain attack and cerebrovascular accident are both alternative names for a stroke. An ischemic stroke is caused by a restriction of oxygen or loss of blood to the tissues of the brain, either by a blocked artery or blood clot. If a portion of the brain does not get enough oxygenated blood, function controlled by that area of the brain will be affected. Our focus at Preventive Heath Advisor is on Integrative Medicine and prevention. However, it is extremely important for the patient who is experiencing the signs of an acute stroke (facial droop, focal weakness, dysarthria of speech) to report to an Emergency Room as soon as possible. An acute stroke should be considered for immediate treatment with thrombolytic therapy or newly available clot retrieval systems within 4.5 hours.

Ischemic stroke is most commonly related to a narrowing or unstable arterial plaque in the arteries of the head or neck. There are two types of ischemic stroke: embolic stroke occurs when a blood clot travels from another location in the body to the brain such as in atrial fibrillation, or thrombotic stroke when a blood vessel plaque ruptures resulting in a clot (or thrombosis). A transient ischemic attack (TIA), sometimes called a mini-stroke, is characterized by symptoms of a stroke which last under 24 hours, and may be a warning sign for a stroke. Within this section, Preventive Health Advisor will include evidence-based methods of lifestyle and risk factor modification for prevention of ischemic stroke. As a general rule, Preventive Medicine, Integrative Medicine, and Lifestyle Medicine treatment methods for coronary heart disease will also reduce the risk of ischemic stroke. Therefore, in addition to this information, please refer to the section on coronary artery disease.

 

Cause of Atherosclerosis:

Atherosclerosis was described by a world renowned Cardiologist, William C. Roberts, MD as the leading cause of heart attacks, stroke, and peripheral vascular disease. This author claimed that cholesterol intake causes atherosclerosis. Roberts is a highly regarded cardiologist with five decades of relevant experience, has over 1300 scientific publications, a dozen cardiology textbooks, and has been editor in chief of the American Journal of Cardiology for 25 years. According to this author, the evidence which supports that cholesterol causes atherosclerosis include a higher frequency of atherosclerotic events in populations with relatively high cholesterol levels compared with populations with relatively low cholesterol levels. Atherosclerosis is easily produced in herbivores (rabbits, monkeys) by feeding them a high-cholesterol (egg yolks) or high-saturated-fat (animal fat) diet. Lowering total cholesterol and low-density lipoprotein (LDL) cholesterol levels decreases first and repeat atherosclerotic events and decreases plaque size. Furthermore, societies with a high frequency of hypertension or a high frequency of cigarette smoking but low cholesterol levels rarely get atherosclerosis. Therefore, to decrease the risk of atherosclerotic events, Roberts recommends that LDL cholesterol needs to be <100 mg/dL and ideally <70 mg/dL. Total cholesterol should be <150 mg/dL, and the high-density lipoprotein (HDL) cholesterol >20 mg/dL. The low HDL goal is rationalized by the author that levels below 20 are not dangerous if LDL and total cholesterol is also low. (1)

 

Ideal cardiovascular health:

The American Heart Association (AHA) developed a construct of “ideal cardiovascular health,” targeting 7 behaviors that raise the likelihood of not having to face cardiovascular disease or stroke. These metrics established by the American Heart Association were applied by Artero, EG et al in The Aerobics Center Longitudinal Study to reduce the risk of cardiovascular mortality. They include 4 core behaviors—no smoking, a normal body mass index (BMI), engaging in physical activity, and eating healthfully—and meeting at least 3 of the following criteria: cholesterol lower than 200 mg/dL, blood pressure lower than 120/80 mm Hg, not having diabetes, or being free of heart disease. To assess the effects of meeting these targets on risk of death from cardiovascular disease, Artero and colleagues looked at data from the Aerobics Longitudinal Study, conducted in 11,993 patients between Oct. 9, 1987 and March 3, 1999. The authors found that those who met 3-4 of AHA’s “Simple Seven” heart health criteria had a 55% lower risk of cardiovascular mortality than those who met no more than 2 of those practices over about 11 years. It was 63% lower for those who fulfilled five to seven of the ideal criteria compared with those with the lowest scores However, the overall prevalence of ideal cardiovascular health was extremely low in this middle-aged cohort, with only 0.2% of patients meeting all 7 criteria. (2)

 

Risk factor modifications for cardiovascular diseases:

According to the American Heart Association (AHA), the key to reduction of cardiovascular disease risk including stroke consists of the following (3): 1) evidence-based dietary changes; 2) cardiopulmonary exercise; 3) achieving healthy bodyweight; 4) favorable lipid panel; 5) maintaining normal blood pressure; 6) avoidance of smoking; and 7) keeping blood glucose levels within normal range. (82)

 

Diet recommendations by the AHA:

American Heart Association (AHA) Scientific Statement, Diet and Lifestyle Recommendations: Revision 2006 by Lichtenstein, AH et al for cardiovascular disease (3):

• Eat a healthful diet the majority of the time including vegetables, fruits, whole grains, fat-free or low fat dairy, beans, lean meat, poultry, and oily fish at least twice weekly. Limit total cholesterol to 300 mg per day for healthy adults and for patients with LDL cholesterol under 100 mg/dl. Limit cholesterol to 200 mg per day for patients with coronary artery disease.
• Total fat intake limited to under 25–35 percent of total calories per day.
• Saturated fat intake limited to under 7 percent of total calories per day.
• Trans fat intake should be under 1 percent of total calories per day.
• Other fat in the diet should come from monounsaturated or polyunsaturated oils from unsalted nuts, seeds, oily fish, and vegetable oil such as canola or olive oil.

 

Maintain a healthy bodyweight:

Maintain a healthy bodyweight with a body mass index (BMI) between 18.5-24.9 kg/m².

The AHA defines overweight as 25-29.9 kg/m², and obesity as greater than or equal to 30 kg/m². BMI can be calculated from the basic formula: [Weight (lb) / (Inches of height)²] x 703. BMI may also be calculated using a commonly available BMI calculator such as that available here: http://www.nhlbi.nih.gov/guidelines/obesity/BMI/bmicalc.htm from the NIH National Heart, Lung and Blood Institute. Please see weight loss in Preventive Health Advisor.

 

BMI and stroke risk:

• Using hazard ratios, Saito, I et al found that the following BMI levels were paired with a higher risk of stroke in men and women compared to a BMI of 23.0-24.9 kg/m² (4):
• BMI of 27.0-29.9 kg/m² was associated with a 9% higher risk of stroke in men and a 29% higher risk in women.
• BMI of over 30.0 kg/m² was associated with a 25% higher risk of stroke in men and had more than double the risk of stroke in women.

 

Achieve lipid profile goals:

Achieve LDL, HDL, triglyceride and total cholesterol goals. The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol has established that the following lipid profile is optimal (as cited in Lichtenstein, 2006): LDL optimal under 100 mg/dl, near optimal 100-129 mg/dL, borderline high 130-159 mg/dL, high 160-189 mg/dL, and very high over 190 mg/dL. No specific goals for HDL and triglycerides exist but HDL under 40 mg/dL for men and under 50 mg/dL for women as wells a s a triglyceride level of over 150 mg/dL are all associated with metabolic syndrome. For more information about treatment of elevated cholesterol levels, please see the hyperlipidemia section of Preventive Health Advisor.

 

Blood pressure goal:

Focus on achieving normal blood pressure. According to the AHA, the lifetime risk of hypertension is about 90% and any elevation above a normal blood pressure of 120 systolic over 80 diastolic increases risk even if elevated into pre-hypertensive levels. For more information, please see the hypertension section of Preventive Health Advisor.

 

Blood glucose levels:

Keep blood glucose in normal range: According to the AHA, normal fasting blood glucose is less than or equal to 100 mg/dL and a fasting blood glucose of greater than or equal to 126 is diagnostic of diabetes. Weight loss, exercise, and avoidance of concentrated sweets can greatly improve control of glucose and insulin resistance. For more information, please see the diabetes mellitus section of Preventive Health Advisor.

 

Exercise goals:

Maintain a physically active lifestyle. Regular activity promotes cardiovascular fitness. For further information about benefits of aerobic exercise or resistance training, please see these sections of Preventive Health Advisor.

 

Smoking:

Patients should be counseled to quit smoking at every clinic appointment. If they don’t smoke, they should be counseled not to start. A combination of several methods should be used to assist in cessation. For instance, combine nicotine replacement with at least one additional method such as an exercise program, medication, hypnosis, or formal counseling such as support groups. The recommendation to counsel patients to stop smoking, stop using tobacco products, and provide methods of cessation is reinforced by the U.S. Preventive Services Task Force. Many resources are available to assist in smoking cessation such as the online sites http://smokefree.gov/ , http://www.cdc.gov/tobacco/campaign/tips/quit-smoking/  and the phone number for free help 1-800-QUIT-NOW. Please see the section on smoking cessation in Preventive Health Advisor.

 

Gender differences in stroke:

Women developed a higher incidence of stroke than men after the age of 65, women tended to have anterior ischemic strokes more frequently than men, and men were found to have cerebellum or brainstem strokes more often than women (5). Please see recommendations by the US Preventive Services Task Force below on the use of aspirin for prevention of stroke in women.

 

Importance of homocysteine levels and stroke:

High homocysteine levels are linked with a higher risk of stroke and coronary artery disease and may be lowered using vitamin B6, vitamin B12, and folic acid (6). Preventive Health Advisor supports monitoring and treating high homocysteine levels for prevention of stroke, and in patients with a high homocysteine level and a history of a cerebrovascular event. Using vitamins for lowering homocysteine levels routinely for prevention of coronary artery disease is not adequately supported by research in lowering the risk of heart disease (6). Patients with elevated homocysteine levels of over 18 micromoles per liter (7), may be considered for daily combination regimen of 2.5 mg of folic acid (vitamin B9), 50 mg of vitamin B6 and 1mg of vitamin B12 (8). This regimen is effective for lowering homocysteine (6). Two meta-analyses containing data from many studies found that folic acid was ineffective alone for preventing stroke unless combined with vitamin B12 and vitamin B6 (9,50), and the greatest benefit was seen in patients compliant with the regimen of 3 vitamins for over 3 years (8). Alternatively, patients with elevated homocysteine should seek food sources containing similar amounts to the recommended doses of folic acid, vitamin B6, and vitamin B12 daily from their diet. Of note, vegetarians especially without dairy intake will need to take an oral vitamin B12 supplement. One serving of milk can provide about half of the vitamin B12 daily allowance, but a higher dose of 1 mg daily is required to lower homocysteine. Please see the sections on these vitamins in Preventive Health Advisor to see food sources containing these vitamins. Patients who will likely benefit the most in treatment for an elevated homocysteine level include adults younger than age 69, those with hyperlipidemia, patients from areas where folic acid-fortified food is not available, and patients not currently taking anti-platelet drugs or cholesterol-lowering drugs (8).

 

Homocysteine and patients at risk of stroke:

A statistically significant positive association between elevated homocysteine (Hcy), an amino acid, and the risk stroke was evaluated in a cohort study of 7,983 individuals (The Rotterdam study). It was estimated that each 1 mmol/L increase in plasma Hcy concentrations were associated with a 6–7% increase in the risk of stroke. Additionally, participants with total Hcy levels above 18.6 micromol/L were at significantly increased risk for heart attack (odds ratio [OR]=2.43) and stroke (OR=2.53). Those with hypertension also had a higher risk. (10)

 

Folic acid homocysteine, and stroke prevention:

A meta-analysis found folate supplementation reduced the risk of stroke by 18%, a significant benefit compared with placebo. An analysis of study characteristics suggested that trials lasting over 36 months demonstrated a significant benefit for folate therapy with a reduce risk of 29% compared to placebo. In addition, compared to placebo, folate was effective only in areas without or with very little grain enrichment (25% reduced risk), where homocysteine was lowered by more than 20% (23% reduced risk), and among patients without a previous history of stroke (25% reduced risk). (11)

Lowering of homocysteine, an amino acid, with folic acid and vitamins B6 and B12 had a modest, but beneficial effect on stroke prevention or fatal stroke among a population at high risk for cardiovascular disease. Results from this five-year research trial that randomly assigned 5,522 adults with heart disease to either placebo or a daily combination regimen of 2.5 mg. of folic acid (vitamin B9), 50 mg vitamin B6 and 1mg of vitamin B12 found that daily supplements of folic acid, vitamin B6, and B12 for 5 years reduced the risk of stroke by 25%. However, no noticeable effect was observed during the first 3 years of supplementation. During a five-year follow-up period, stroke occurred in 258 of the participants (4.7%). The risk was lower in those who followed the vitamin regimen. The average homocysteine concentration decreased by 2.2 micromol/L in the vitamin therapy group, and increased by 0.80 micromol/L in the placebo group. Those who benefited the most from the vitamin treatment included those younger than age 69, with higher cholesterol and homocysteine levels at the start of the study, from areas where folic acid-fortified food isn’t available, and who weren’t receiving anti-platelet drugs or cholesterol-lowering drugs at the start of the study. (8)

 

Homocysteine and neurodegenerative diseases:

Human studies suggest that homocysteine (Hcy), an amino acid, plays a role in brain damage, cognitive decline and is a risk factor for neurodegenerative diseases such as Alzheimer’s disease, vascular dementia, and  stroke. Numerous studies in recent years investigated the role of Hcy as a cause of brain damage. A meta-analysis of 8 randomized treatment trials (n=37,485) looked at the link between B-vitamins (folic acid, vitamin B6 and/or B12) and risk of stroke, cancer, and vascular diseases found a non-significant decrease in the risk of stroke from B-vitamins. According to the authors, in studies of folic acid and stroke risk, folic acid was found to have a slight benefit, but the results were not significant. Results were better when folic acid was tested in combination with other vitamins (B6 and B12) (12).

 

Evidence-based diet and exercise combination programs:

Diet and exercise combination programs such as the Pritikin Program, The Dr. Dean Ornish Program, and the Therapeutic Lifestyle Changes Diet have all been traditionally prescribed for coronary artery disease, but will also improve many of the risk factors for ischemic stroke. The basics of these programs are included below.

 

The Pritikin Program evidence-based benefits:

A study using 67 patients with metabolic syndrome to investigate the effects of Pritikin therapy for 12-15 days showed improvement in most heart disease risk factors, including body mass index (3% reduction), blood pressure, glucose and LDL cholesterol (10%-15% reduction), and triglycerides (36% reduction). Additionally, 37% of subjects no longer met the criteria for metabolic syndrome as determined by the National Cholesterol Education Program. HDL cholesterol decreased by 3%. (13)

The Centers for Medicare and Medicaid Services review of published data on the Pritikin intensive cardiac rehabilitation programs found that it effectively slowed or reversed progression of coronary heart disease and reduce the need for coronary artery bypass grafts (CABG) and percutaneous interventions. Other benefits identified included reduced LDL cholesterol levels, body weight, blood pressure, rates of angioplasty procedures and the need for cholesterol, blood pressure, and diabetes medications. (14)

The Pritikin Program lowered total cholesterol and LDL cholesterol, lowered blood pressure, better control of insulin levels (control type 2 diabetes), decrease in the circulating levels of compounds that increases the risk of heart disease and blood vessel damage, reduction in the risk of heart disease, hypertension, type 2 diabetes, breast cancer, colon cancer, and prostate cancers. (15)

 

Pritikin Diet characteristics (13,14,15):

• Diet plus exercise counseling for three to four weeks.
• Very low fat, less than 10% of calories compared to 35% in the normal American diet.
• Low sodium intake and avoidance of salty foods.
• High fiber with at least five ½-cup servings of whole grains daily (wheat, oats, and brown rice or starch vegetables such as potatoes, and dried beans and peas.
• Refined grain products (white flour, regular pasta, white rice) are limited to two servings daily.
• At least four 1-cup servings of raw vegetables daily or ½-cup servings of cooked vegetables. Dark green, leafy, and orange or yellow vegetables are preferred
• At least three servings of fruit, one of which can be fruit juice.
• Two servings daily of calcium-rich foods such as nonfat milk, nonfat yogurt or fortified and enriched soymilk.
• No more than one caffeinated drinks daily. Instead drink water, low-sodium vegetable juices, grain-based coffee substitutes or caffeine-free teas.
• No more than four alcoholic drinks per week for women and no more than seven for men, with red wine preferred over beer or distilled spirits.
• No more than seven egg whites per week.
• no more than 2 ounces (about 1/4 cup of nuts) daily.
• Moderate amounts of fish, nonfat dairy, and lean meat with no more than one 3.5 cooked serving of animal protein per day with fish and shellfish are preferred. Lean poultry should optimally be limited to once a week and lean beef to once a month.
• Adapted to vegetarians by replacing animal protein with protein from soy products, beans, or lentils.
• Avoid fried foods, dressing with fat, and fatty sauces, animal fats, processed meat, dairy products not made with non-rat milk, egg yolks, salty snacks, cakes, cookies, and similar high-calorie choices.
• Eat frequently with three meals a day plus two snacks.
• Artificial sweeteners such as Splenda are okay.
• Exercise component of the Pritikin Program: The exercise component includes 45 minutes of moderate exercise daily such as walking.
• Insurance approval for the Pritikin Program: Medicare may approve coverage for the Pritikin Program for qualifying individuals with a history or risk of cardiovascular events. The program has been approved for coverage under Part B of Medicare. Medicare will reimburse eligible beneficiaries for up to 72 one-hour ICR sessions, up to 6 sessions per day, at the Pritikin Longevity Center & Spa.

 

The Dean Ornish Program for Reversing Heart Disease (16):

The Ornish program evidence-based benefits:

• Ornish Program findings of 3,780 patients found that the average patient lost 13.3 pounds in the first 12 weeks and 15.9 pounds after 1 year.
• Significant reductions in systolic blood pressure (BP), diastolic BP, total cholesterol, triglycerides, and LDL-cholesterol after 12 weeks were still significant after 1 year.
• Exercise capacity increased by 18% after 12 weeks and 24% after one year.
• Reductions in depression were still significant after 1 year.
• Hemoglobin A1C in diabetics continued to decrease after one year.
• 5% of patients reported improvement in severity of angina (chest pain) after 1 year.

 

Ornish Program characteristics:

The Ornish program teaches a plant-based, meatless diet, meditation, and regular exercise with adherence to the program between 85 to 90% after one year in hospitals and clinics that have offered it.

Insurance approval for the Ornish Program: Medicare Part B covers The Dean Ornish Program for Reversing Heart Disease, under a new benefit category, Intensive Cardiac Rehabilitation (ICR). Eligibility includes acute myocardial infarction within the preceding 12 months, a coronary artery bypass surgery, current stable angina pectoris, heart valve repair or replacement, percutaneous transluminal coronary angioplasty or coronary stenting, a heart or heart-lung transplant, or other cardiac conditions as specified through a national coverage determination. (16)

 

The Therapeutic Lifestyle Changes Diet for coronary heart disease (17,18):

• Consistent with the American Heart Association’s 2006 Diet and Lifestyle Recommendations which can reduce the risk of cardiovascular disease.
• The diet consists of cutting back sharply on saturated fat, which may elevate LDL cholesterol levels and increase the risk of heart attack and stroke. Intake of saturated fat is kept below 7% of the total calorie intake. Total fat intake should consist of 25-35% of daily total calories.
• Daily cholesterol intake should be kept below 200 milligrams.
• Sodium intake is limited to 2400 mg per day. Calorie intake should be kept to a level needed for maintaining healthy weight and reduce blood cholesterol level. (18)

 

Exercise and the Therapeutic Lifestyle Changes Diet (TLC):

The effect of adding 30 minutes of daily exercise at 50-75% of age-predicted maximum heart rate, to a Therapeutic Lifestyle Changes Diet (TLC) for 6 months was examined by Welty, FK et al. The authors of the study randomized participants with high-normal or stage 1 hypertension to either a treatment diet rich in fruit, vegetables, low-fat dairy products, reduced saturated/total fat or a control diet low in fruit, vegetables, and dairy products with fat content typical of the average US diet. A TLC diet with the addition of exercise assisted 89% of participants to reach an LDL cholesterol goal of under 130 mg/dL without lowering HDL levels or needing to add or increase lipid lowering therapy. The authors emphasized that exercise and weight loss should be encouraged with the TLC diet to achieve the LDL goal. Mean total cholesterol, LDL cholesterol and triglycerides decreased by 9.2% (p=0.08), 9.3% (p<0.018), and 18.8% (p<0.05), respectively; mean HDL cholesterol increased 2.6% (p=0.41). Women had a 12.3% reduction in LDL cholesterol and an 11.4% increase in HDL cholesterol compared with a 7.9% reduction in LDL cholesterol and no change in HDL cholesterol in men. Additionally, systolic and diastolic blood pressure (BP) decreased 9% (p<0.001) and 13%, respectively (p <0.0001). These BP reductions were two-fold greater than in the Diet and Systolic Hypertension study (DASH) The addition of exercise also achieved a 50% reduction in angina. (17)

 

Specific evidence-based dietary modifications for cardiovascular disease and stroke:

Mediterranean diet and stroke:

A Mediterranean style diet generally consisted of a variety of fruits, vegetables, whole grains, olive oil, legumes, nuts, beans, herbs, seeds, and spices as the primary basis for each meal. Fish and seafood is eaten often at least twice per week. Yogurt, poultry, eggs, and cheese is consumed in moderate portions daily to weekly. Meats and sweets are eaten infrequently. (19)

Hoevenaar-Blom, MP et al followed patients for 10-15 years on a Mediterranean style diet with moderate alcohol consumption and determined that the patients with a compliance to this diet over this time period in terms of hazard ratios, had a 12% lower risk of stroke, 14% lower risk of myocardial infarction, 22% lower risk of fatal cardiovascular diseases, and 26% lower risk of coronary artery disease. Adherence to this diet did not reduce the risk of total amount of cardiovascular diseases and the number of transient ischemic attacks were not reduced with the Mediterranean diet. (20)

A review of research by Foroughi, M et al on stroke and nutrition found that a Mediterranean style diet or DASH (dietary approaches to stop hypertension) diet may reduce ischemic stroke incidence (21). Please see the section on hypertension to review the DASH diet in detail.

 

Nut consumption and risk of stroke:

Consumption of almond and walnuts instead of more traditional fats, is linked to an 8% to 12% reduction in LDL cholesterol (22). Epidemiologic and clinical studies have reported consistently that Americans who eat five or more servings of nuts per week have a 35% reduced risk of coronary heart disease (44), with some research reporting up to a 50% lower risk (22). Few studies exist on the association of nut consumption with the risk of stroke and more research needs to be performed. One epidemiological study showed no association between nut intake and ischemic stroke, but noted instead that there may be an association of nut intake with hemorrhagic stroke in a “j-type” distribution according to the authors of the study (23).

 

Fiber intake and cardiovascular disease:

Fiber intake may reduce the risk of both ischemic stroke and ischemic heart disease. A meta-analysis of cohort studies found that an increase in total fiber intake of 7 grams per day was associated with a 7% lower risk of stroke (24). An increase in dietary fiber intake is recommended as part of the diets discussed above due to their ability to reduce the risk of cardiovascular disease. Fruits and vegetables contain a large amount of fiber. Eight published cohort studies found that fruit and vegetable intake resulted in an overall reduction in the risk of developing ischemic heart disease by approximately 20% (25)

 

Vegetarian diet and stroke:

A meta-analysis consisting of 7 studies with a total of 124,706 participants from the UK, Germany, USA, Netherlands and Japan was conducted to investigate cardiovascular disease mortality and cancer incidence among vegetarians and non-vegetarians. All-cause mortality, mortality from circulatory diseases, and mortality from cerebrovascular diseases in vegetarians were lower when compared to non-vegetarians by 9%, 16%, and 12%, respectively. This study suggested that vegetarians have a mortality advantage compared to non-vegetarians. (26)

 

Whole grain consumption and risk of cardiovascular disease:

A meta-analysis examined evidence on whole grain intake and cardiovascular disease (CVD). Seven prospective cohort studies with measures of dietary whole grains and cardiovascular outcomes were identified. Researchers found that greater whole grain intake (average 2.5 servings per day vs. 0.2 servings per day) was associated with a 21% lower risk of CVD events. The findings were similar for both men and women and CVD events including heart disease, stroke, and fatal CVD events. (27)

 

Antioxidants for prevention of cardiovascular disease:

For the prevention of cancer or cardiovascular disease, the U.S. Preventive Services Task Force (USPSTF) recommends against the use of beta-carotene supplements, alone or in combination. According to the USPSTF, there is insufficient evidence to recommend for or against the use of vitamins A, C, or E supplements or multivitamins with folic acid or antioxidant combinations for the prevention of cancer or cardiovascular disease. (28)

Beta carotene and cardiovascular disease: There is some evidence that suggests fruit and vegetable based beta-carotene is associated with lower risk of cardiovascular disease.

Beta carotene intake in the form of vegetables was associated with a lower risk of cardiovascular and cancer mortality and with a lower risk for death from all causes (29).

For more information, please see beta-carotene section of Preventive Health Advisor.

 

Vitamin D, stroke, cardiovascular mortality and all-cause mortality:

For more information, please see vitamin D section of Preventive Health Advisor.

Maintain favorable levels of vitamin D in all patients with any risk factors for cardiovascular disease. Vitamin D is not established as a direct cause of cardiovascular disease, but vitamin D deficiency is associated with a higher incidence of hypertension, hyperlipidemia, coronary artery disease, stroke, chronic kidney disease, and diabetes mellitus type 2 (30).

Sun and colleagues evaluated the associations between both dietary and supplemental vitamin D and cardiovascular disease risk. Researchers evaluated data on 74,272 women and 44,592 men who were initially heart disease and cancer-free from the Nurses’ Health Study (1984-2006) and the Health Professionals Follow-Up Study (1986-2006). After about a 20 year follow-up period, 9,886 cases of coronary heart disease and stroke were documented.  The researchers found a 16% reduction in heart disease among men who met the Dietary Reference Intake (DRI) of vitamin D of at least 600 IU per day, as compared to men with daily intakes of less than 100 IU. The researchers found that men who consumed larger amounts of vitamin D had a decreased risk of heart disease. There was no association between vitamin D intake and heart disease risk for women. (31)

In a study on adult men, Michaëlsson K et al found that a vitamin D concentration of 24 to 34 ng/ml (60 to 85 nmol/L) approximately translates to a vitamin D dose of 2000 IU/d and corresponded to the lowest cardiovascular-related and all-cause mortality (32). Overall mortality was increased by 50–60% among a population of subjects in the lowest 10% and highest 5% of the vitamin D level curve distribution, whereas cardiovascular mortality was increased only in the bottom 10% (32). Vieth reported that the ideal level of vitamin D intake for adults should be 50 mg (2000 IU) per day (33). Bosomworth NJ conducted a review of multiple studies, and determined that 500-1500 IU/d of vitamin D reduced all-cause mortality (34).

Diabetes mellitus patients have been noted to have lower vitamin D levels and are at a higher risk of stroke than non-diabetics. A retrospective analysis showed that patients with diabetes mellitus have a very low 25-hydroxy vitamin D level, and also found that high levels of triglycerides, LDL cholesterol, and HbA1C had a consistent association with vitamin D deficiency in type 2 diabetes patients (35).

Vitamin D and hypertension: Please see the hypertension section of Preventive Health Advisor

 

Wine consumption and cardiovascular disease risk:

A study done in Copenhagen, Denmark followed 6051 men and 7234 women between 30 and 70 years old. The relative risk of cerebrovascular mortality was significantly less for those who had a low to moderate intake of wine. It was found that beer intake did not change mortality risk much and that drinking spirits increased mortality. (36)

Moderate red wine consumption has been associated with decreased cardiovascular risk, reduced mortality, and improved cholesterol profile. Multiple studies have shown that red wine is more beneficial in reducing the risks of mortality in general when compared with other alcoholic beverages such as spirits, beer and white wine. HDL cholesterol has been found to be increase with red wine consumption in numerous studies. (37)

A parallel four-armed intervention studied the relationship between cardiovascular disease (CVD) and wine drinkers. Sixty-nine men and women aged 38-74 years old were randomized to either 1: red wine (males: 300 ml/day, 38.3 g alcohol/day, female subjects: 200 ml/day, 25.5 g alcohol/day), 2: water + red grape extract tablets (wine-equivalent dose), 3: water + red grape extract tablets (half dose), or 4: water + placebo tablets. At the end of the 4-week study period, results showed that moderate alcohol consumption in the form of red wine is associated with beneficial changes in blood lipids and fibrinogen that may help to reduce the risk of cardiovascular disease. (38)

The relation between red wine in the form of polyphenolic extracts and risk factors associated with cardiovascular disease was examined in a European project FAIR CT 97 3261. Results from a study of 40 healthy volunteers in Barcelona showed a significant increase in HDL cholesterol levels and a decreased oxidation of LDL cholesterol after red wine consumption (30 g alcohol daily for 4 weeks) as compared to the same amount of alcohol given as spirit such as vodka, whiskey, gin, tequila, and rum. Additionally, according to the authors, a meta-analysis indicated a significant negative relationship between moderate wine drinking of 150-300 ml daily and the risk of cardiovascular events. The study concluded that moderate wine consumption is linked with prevention of cardiovascular disease. (39)

The effects of dealcoholized red wine (DRW) and regular red wine (RW) on risk factors associated with cardiovascular disease in 45 hypercholesterolemic postmenopausal women were analyzed. Participants were randomized to 400 mL/day of either water, DRW or RW for 6 weeks on a controlled diet following a 4-week washout. At the end of the study period, concentrations of fasting lipids, lipoproteins, insulin and glucose were unaffected by DRW intake. However, chronic consumption of RW significantly decreased LDL cholesterol concentrations by 8% and increased HDL cholesterol concentrations by 17%.  In summary, regular consumption of red wine reduces cardiovascular disease risk by improving fasting LDL and HDL levels in hypercholesterolemic postmenopausal women. (40)

Men who consumed light-to-moderate amounts of alcohol at 3–4 or 5–7 days per week had decreased risk of ischemic stroke compared with men who consumed alcohol less than once per week. Moderate alcohol drinking decreases the risk of cardiovascular disease by about 25%, which is linked to a decrease in the total cardiovascular disease burden in Australia of about 4.7%. In 2008, 34% of the total number of deaths in Australia were related to cardiovascular disease and in 2003, it was 18% of the overall burden of disease. Coronary heart disease and stroke contributed to over 80% of this burden. Alcohol consumption decreases the risk of cardiovascular disease. (41)

 

Chocolate consumption and risk of stroke:

Consumption of chocolate has been found to significantly reduce the risk of both ischemic stroke and hemorrhagic stroke in a large cohort study of women who ate a median of 66.5 grams per week of chocolate (42). In a large cohort study on men, a median intake of 62.9 grams of chocolate per week was associated with a decrease in risk of stroke by about 17% (43). Chocolate has also been noted to decrease the risk of coronary heart disease in subjects compared to others who did not consume chocolate (44). Cocoa is believed to improve blood flow by counteracting endothelial dysfunction by the action of flavonols which naturally occur in cocoa and possess antioxidant characteristics (45).

 

Caffeine consumption and cardiovascular disease risk:

In a population study researchers found that consumption of coffee, green tea and oolong tea and total caffeine intake was linked to a reduced risk of death from cardiovascular disease (CVD). Participants included 76,979 adults followed for 1,010,787 person years, all of whom were ages 40 to 79 and free of stroke, heart disease, and cancer at the start of the study. Researchers determined that compared to non-coffee drinkers, men consuming 1-6 cups/week, 1-2 cups/day and ≥ 3 cups/day had a protective effect from coffee with a 22%, 33%, and 55% less rate of stroke occurrence than the control population. The multivariate hazard ratio,(HR), (or ratio of hazard rates from coffee drinkers to non-coffee drinkers) was 0.78 (range 0.50 to 1.20), 0.67 (range 0.47 to 0.96) and 0.45 (range 0.17 to 0.87) respectively for strokes among men (p = 0.009). Compared with non-tea drinkers, women consuming 1-6 cups/week, 1-2 cups/day, 3-5 cups/day and ≥ 6 cups/day had a 66%, 72%, 61%, and 58% reduced rate of coronary heart disease compared to non-tea drinkers. Multivariable hazard ratios were 0.34 (0.06-1.75), 0.28 (0.07-1.11), 0.39 (0.18-0.85) and 0.42 (0.17-0.88) respectively(p = 0.038 for trend). Men drinking ≥ 1 cups/day of oolong tea benefited from a 61% reduced rate of CVD (the HR was 0.39, with range of 0.17-0.88) when compared to non-tea drinkers, (p = 0.049 for trend). Individuals in the second highest quintile of total caffeine intake had a total CVD risk reduction of 38% in men and 22% in women. (46)

According to James J. E. , caffeine, through its daily consumption from a variety of sources (coffee, teas, soft drinks, chocolate and medicines), may have an impact on cardiovascular risk. This fact is related to the evidence found the scientific literature about the ability of caffeine to increase resting blood pressure (BP) in adults by about 4/2 mmHg. However, this increase in BP could be responsible for premature deaths of about 14% for coronary heart disease and 20% for stroke. (47)

 

Tea consumption, stroke, and cardiovascular disease:

Authors analyzed fourteen studies (with a total of 513,804 participants) written from January 1966 to March 2012 to examine the relationship between green and black tea consumption and risk of stroke in a meta-analysis. They found that as tea consumption increased the risk of stroke decreased.  Increasing tea consumption by 3 cups a day was associated with a 13% decrease in risk of stroke (RR=0.87). Additionally, results from three papers indicated that as tea drinking increased, this did not necessarily reduce the risk of strokes due to bleeding (cerebral hemorrhage and subarachnoid hemorrhagic strokes). (48)

A case-control study tracked frequency and duration of tea drinking, quantity of dried tea leaves, and types of tea consumed, habitual diet and lifestyle characteristics among 374 ischemic stroke (IS) patients in China from 2007 to 2008; 464 control subjects were also recruited. Researchers found that the risk of ischemic stroke decreased with the increase in the frequency of tea consumption (OR=0.61), duration of tea consumption (OR=0.40) and the increase in the amount of tea leaves brewed (OR-0.27). Additionally, when compared with infrequent or nondrinkers, there was a significant decrease in risk of ischemic stroke associated with drinking at least one cup of tea weekly (P=0.015). Risk reduction was greatest among those drinking one to 2 cups of green or oolong tea daily. (49)

Consuming green tea is associated with a reduced risk of death from heart disease as well as from all-cause mortality. Researchers followed 40,530 Japanese adults up to 11 years. The results indicated that individuals who consumed the most green tea had lower death rates from cardiovascular disease (CVD) compared to subjects who consumed the least green tea (less than 1 cup/day). Women who drank ≥ 5 cups/day of green tea had a 31% lower risk of dying from CVD and a 23% lower risk of mortality from all causes than women who drank <1 cup/day. Those who drank 1 to 2 cups/day or 3 to 4 cups/day green tea had a 2% and 18% reduced risk of all-cause mortality, respectively. Corresponding risk reductions in CVD were 16% and 31%. The protective effect of green tea was stronger in women than in men. In men who drank ≥ 5 cups/day of green tea, all-cause mortality rate was noted to fall by 12%. Men who drank 1 to 2 cups/day or 3 to 4 cups/day green tea had a 7% and 5% reduced risk of all cause-mortality, respectively. Green tea consumption was not associated with a reduction in cancer mortality. (51)

 

Aerobic exercise for disease prevention and treatment:

Seek approval by primary physician prior to starting an exercise program. Aerobic exercise generally consists of mild to moderate intensity activity with rhythmic contraction of major muscle groups over an extended period of time. Examples include fast walking, jogging, cycling, Zumba, cross country skiing, and swimming. For the  physician or fitness professional, the following source is the most credible reference for initiation of exercise in patients: Walter R. Thompson, American College of Sports Medicine, Neil F. Gordon, Linda S. Pescatello. ACSM’s Guidelines for Exercise Testing and Prescription. Lippincott Williams & Wilkins, Feb 1, 2009. (52)

 

Benefits of aerobic exercise:

The data provided below illustrates many benefits of aerobic exercise in cardiopulmonary (heart and lung) conditioning, improved pumping efficiency of the heart, improved circulatory system (53), weight control (54), cholesterol reduction (54,55), triglyceride lowering (54), lowering of blood pressure (56), lower rate of smoking (57),  and control of diabetes (58,59). Aerobic exercise results in reduction of cardiac mortality and all-cause mortality (57).

According to the World Health Organization: According to the World Health Organization, regular exercise is recommended for not only all healthy individuals, but also those suffering from obesity, diabetes, hypertension, atherosclerotic cardiovascular disease and cancer. (60)

 

Starting exercise in apparently healthy adults:

According to the American College of Sports Medicine (ACSM) and the American Heart Association (AHA): Older adults need moderate-intensity (between 5-6 on a 10-point scale) aerobic endurance activity for a minimum of 30 min which can be achieved in short 10 minute sessions on five days each week or vigorous-intensity aerobic, (rated a 7-8 on a 10-point scale) activity for a minimum of 20 min on 3 days each week.  Adults should also perform muscle-training exercises 2-3 days each week using a variety of exercises (8-10 exercises involving the major muscle groups). For each exercise, 10-15 repetitions are recommended to improve strength. Additionally, older adults at risk of falling should do flexibility exercises at least 2 or 3 days each week to maintain or improve balance. (55)

Amount of activity according to the World Health Organization: The most benefit from physical activity is achieved with at least 2.5 hours of aerobic exercise of moderate intensity per week, which can be accumulated in 10-minute periods. At least 2 days/week vigorous intensity aerobic exercise and resistance exercises for muscle strengthening are recommended. Increased intensity, frequency and duration of exercise is associated with increased added health benefits. (60)

Power walking is an effective initial aerobic activity for beginners. One may start walking at a normal pace and continue to increase the walking speed over 10 minutes to reach a heart rate of 110 – 120 beats per minute resulting in perspiration.

 

Starting exercise in chronically ill patients:

Exercise guidance in patients with serious illnesses and for those with specific medical problems: The most respected credible source available for exercise prescription is Thompson et al, American College of Sports Medicine’s (ACSM’s) Guidelines for Exercise Testing and Prescription (61). This source should be consulted for advice when recommending exercise to patients with specific serious illnesses. Another valuable source is Gauer, RL and O’Connor, FG with Department of Family Medicine Uniformed Services University of the Health Sciences, “How To Write An Exercise Prescription.” (62) This can be accessed at: http://www.move.va.gov/download/Resources/CHPPM_How_To_Write_And_Exercise_Prescription.pdf

 

Risk of exercise exceeds the benefits in the following medical conditions:

In patients suffering from a recent heart attack, unstable angina, ventricular arrhythmias, any tear in the inner layer of the aorta, aortic aneurysm, congestive heart failure, severe aortic stenosis, inflammation of the heart muscle or pericardium, pericarditis, pulmonary embolism, intracardiac thrombi, blockage of the main artery of the lung or one of its branches, and acute infection should not exercise since the risks of exercise exceed the benefits. Again, if any of these health conditions are present in an individual a health provider prior should be consulted before any exercise and the physician should refer to the ACSM’s guidelines for exercise testing and prescription (61):

 

The following medical conditions may increase the risk of complications during exercise:

In the following medical conditions, exercise may increase the risk of complications but may still be beneficial. These conditions include untreated or uncontrolled high blood pressure, moderate aortic stenosis, severe narrowing of the left ventricle of the heart just below the aortic valve, mitral stenosis, atrial arrythmias, swelling of a blood vessel in the heart that occurs after a heart attack, ventricular bigeminy or trigeminy, frequent premature ventricular contractions, deterioration of the heart muscle, metabolic disease (diabetes, thyroid disease, etc) or electrolyte abnormality, chronic or recurrent infectious disease such as malaria and hepatitis, neuromuscular, musculoskeletal or rheumatoid diseases made worse by exercise, or complicated pregnancy. If any of these health conditions are present, the physician should refer to the ACSM’s guidelines for exercise testing and prescription. (61)

 

Additional topics for exercise in chronically ill patients:

For the following topics, please see the aerobic exercise section in Preventive Health Advisor; cardiac stress testing referral, clinical cardiopulmonary exercise testing, medication effect during exercise, and evidence-based benefits of aerobic exercise.

 

Aspirin for prevention of cardiovascular disease and stroke according to the U.S. Preventive Services Task Force (USPSTF) (63):

Ideal dose of aspirin: According to the USPSTF, the ideal dose of aspirin is not known, but a dose of 75 mg per day appears as effective as higher doses and may have less risk of gastrointestinal bleeding.

 

The USPSTF recommendation for prevention of cardiovascular disease in men:

Men younger than 45 years: For myocardial infarction prevention in men younger than 45 years the USPSTF recommends against the use of aspirin since the benefit for prevention of cardiovascular events are small.

Men age 45 to 79 years: The USPSTF strongly recommends the use of aspirin when the potential benefit due to a reduction in myocardial infarctions is more beneficial than the potential harm due to gastrointestinal hemorrhage.

The USPSTF recommendation for prevention of cardiovascular disease for the elderly: Men and Women 80 years of age and older: According to the USPSTF, there is insufficient evidence to determine the risk verses benefit of taking aspirin by men and women over 79 years of age for the prevention of cardiovascular disease.

 

Aspirin and prevention of ischemic stroke in women:

• Cardiovascular events were not reduced in women by aspirin and therefore they are not believed to benefit from aspirin for heart disease but women do benefit from aspirin in the prevention of ischemic stroke.

 

• Women age 55 to 79 years: The USPSTF strongly recommends aspirin when the potential benefit due to a reduction in ischemic strokes (which occur when an artery to the brain is blocked) is more beneficial than the potential harm due greater gastrointestinal hemorrhage.
• Women 55 years old or younger: The USPSTF recommends against the use of aspirin for stroke prevention since the benefit for prevention of ischemic stroke is small.

 

Atrial fibrillation:

Patients with atrial fibrillation are at a higher risk for stroke between 1-20% per year or 4.5% on average depending on the presence of additional risk factors and medical problems. For detailed information on prevention of stroke with anticoagulation including warfarin (Coumadin), antiplatelet agents (aspirin and clopidogrel) and new recommendations for dabigatran, please see the American Heart Association/American Stroke Association (AHA/ASA) “Guidelines for the Primary Prevention of Stroke” available at http://www.ncbi.nlm.nih.gov/pubmed/22858728 or http://stroke.ahajournals.org/content/43/12/3442.full (64).

 

Prediction of ischemic stroke:

A CHADS2 score is the most accurate tool for prediction of stroke in patients with atrial fibrillation (65). Calculating a CHADS2 score uses the following scoring system (129):

• 2 points for previous stroke or TIA (transient ischemic attack)
• 1 point for recent CHF (congestive heart failure)
• 1 point for hypertension
• 1 point for age 75 years or older
• 1 point for diabetes

 

Rate of stroke by CHADS2 score:

The rate of stroke occurrence without anticoagulation per year depends upon the CHADS2 score as follows (65):

• CHADS2 score of 0: 1.9% per year.
• CHADS2 score of 1: 2.8% per year.
• CHADS2 score of 2: 4.0% per year.
• CHADS2 score of 3: 5.9% per year.
• CHADS2 score of 4: 8.5% per year.
• CHADS2 score of 5: 12.5% per year.
• CHADS2 score of 6: 18.2% per year.

 

Treatment for prevention of ischemic stroke in patients with atrial fibrillation:

• The patient’s cardiologist and primary care provider are responsible for recommending treatment for the prevention of stroke. According to the American Heart Association/American Stroke Association (AHA/ASA) basic treatment guidelines are as follows (64):
  • CHADS2 score of 0: No treatment or aspirin is recommended.
  • CHADS2 score of 1: Antithrombotic therapy choice by the physician varies.
  • CHADS2 score of 2 or higher: Anticoagulation is recommended for atrial fibrillation to prevent stroke.

 

Warfarin, aspirin, and clopidogrel use in risk of stroke:

Warfarin with dose changes to maintain therapeutic range reduced the risk of stroke in atrial fibrillation from an average of 4.5% to 1.4%. Aspirin reduces the risk of stroke in atrial fibrillation by about 21%. Benefit verses risks of bleeding or adverse effects from anti-thrombotic therapy should be discussed in detail with the physician. The risk of severe bleeding episodes while taking warfarin was about 1.3% per year, and with aspirin, about 1% per year. Therapy with both aspirin and clopidogrel were demonstrated to be about the same severe bleeding risk as warfarin with a small reduction in stroke rates.

 

Creatine phosphate and atrial fibrillation:

Creatine has been shown to have lower rates of arrhythmias before and after heart surgery, but creatine phosphate has not been studied yet for use in atrial fibrillation, but should be investigated. Three days before surgery, creatine phosphate supplementation showed improved heart function after bypass surgery with less ventricular arrhythmias and reduced use of inotropic drugs (66). Creatine phosphate given during cardiac surgery and the early postoperative period reduced CK and CKMB levels plus resulted in a lower percentage of arrhythmias compared to controls (67).

 

Omega-3 fatty acids and stroke:

Omega-3 fatty acids appear to have more benefits in improvement of heart disease than stroke. Many benefits of omega-3 fish oil are included below, but research is mixed showing many trials and meta-analyses with positive findings, but others lacked in showing a benefit. Also, please see the coronary artery disease section for more information.

 

American Heart Association (AHA) fish, fish oil, and oil intake (68):

Omega-3 fish oil is beneficial for treatment of elevated triglycerides. Patients needing triglyceride lowering, should have fish oil prescribed by a physician. The AHA recommends a daily intake of 2-4 grams of EPA+DHA for elevated triglycerides, but a patient prescribed over 3 grams of omega-3 fish oil should be overseen by a physician due an increased risk of bleeding.

 

Omega-3 fish oil benefits:

Omega-3 fish oil is associated with a reduction in total mortality (69,70,71), lower risk of sudden death (69,71), lower risk of nonfatal MI (70), lower risk of nonfatal stroke (70), 20% reduction in deaths from cardiac causes (72), if taken within 18 hours of myocardial infarction symptoms noted a reduction in total cardiac events (73), reduction in total angina pectoris (73), reduction in cardiac arrhythmias (73), and lower risk of left ventricular enlargement (73).

 

Omega-3 fish oil was not found to be beneficial in some research:

Some studies showed no benefit for reduction in stroke (74), no decrease in nonfatal heart attacks (69), no reduction in all-cause mortality (72), no reduction in total cardiac deaths (73), and some showed no benefit in terms of arrhythmic events (72).

 

Omega-3 fish oil, vitamin E, and stroke:

In a randomized controlled trial called the GISSI-Prevenzione trial done in Italy, 11,324 patients with pre-existing coronary heart disease (CHD) were randomly allocated to either 300 mg vitamin E, 850 mg omega-3 fatty acid ethyl esters (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), both, or no treatment and followed for 3.5 years noted the following results (71):

• Reduction in nonfatal stroke was seen in participants taking 850 mg omega-3 fatty acid alone.
• Participants taking omega-3 fatty acid after 6-months experienced a 2.5% increase in HDL cholesterol and a 4% reduction in triglycerides.

 

Fish intake and stroke:

Fish intake has been associated with a 29% reduction in mortality risk over 2 years when eating three fish meals a week (75). An inverse association has been noted between fish intake and coronary heart disease mortality (76).

 

Omega-3 fish oil and atrial fibrillation:

Supplementation with 1 gram of omega-3 fish oil for 1 year did not reduce the incidence of recurrent atrial fibrillation (77). Few studies have shown benefit of using omega-3 fish oil for prevention or recurrence of atrial fibrillation (72).

 

Omega-3 fish oil adverse reactions and interactions:

• A total of 10 studies were reviewed by Villani AM et al to determine potential serious adverse effects of fish oil at a dose of under 1.86 grams per day (78). It was found that there were no serious adverse effects reported in 994 adults over 59 years of age and other non-serious adverse effects were not significantly different from placebo (78).
• Fish oil has been reported to affect platelet aggregation, reduce vitamin K dependent factors which may be associated with an increased anticoagulation (reduce blood clotting) effect. Consumption should be avoided when taking anticoagulants like aspirin, warfarin, or ticlopidine because of the potential increased risk of bleeding (79).
• A case of a 67-year old woman taking warfarin (1.5 mg/day), an increase in her fish oil intake from 1 g/day to 2 g/day was associated with an increase in time for blood to clot as measured by the international normalized ratio (INR) which went from 2.8 to 4.3 within 1month, and decreased to 1.6 after the fish oil dose was reduced (80).
• An intake of 6 grams per day of docosahexaenoic acid (DHA) found no significant difference found in blood coagulation, platelet function, or thrombotic parameters including prothrombin time, activated partial thromboplastin time, antithrombin-III levels, and platelet aggregation (81).
• Fish oil may contain harmful contaminants such as heavy metals including mercury, dioxins, and polychlorinated biphenyls (PCBs). This risk can be reduced by purchasing fish oil that has undergone a purification process specified on the label (approved by the FDA, EPA, or US Pharmacopeia) (82)

 

Calcium intake, cardiovascular disease, and stroke:

Research shows that potential health risks occur with taking calcium supplements. As a result, it is advisable for men and women to avoid a total daily calcium intake of over 1400 mg per day from diet and supplements due to an increased risk of cardiovascular mortality. Preventive Health Advisor supports obtaining the recommended daily intake of calcium from food sources rather than supplements, but not to exceed calcium intake of over 1400 mg per day. Calcium supplements are not advised until further research clarifies these findings. Risk may outweigh the benefits especially if the amount of calcium taken in the diet is unknown.

 

High-dose calcium supplementation and stroke mortality:

High-dose calcium supplementation was associated with greater cardiovascular (CV) mortality and all-cause mortality in women according to a prospective cohort study of 61,433 women born between 1914 and 1948. Compared with dietary calcium intakes of 600 to 1000 mg daily, daily intakes of over1400 mg were associated with significantly higher rates of death from all causes (40% increased risk), CV disease (49% increased risk), and ischemic heart disease (2 times higher risk), but not from stroke. Among the 6% of participant women using calcium supplements (500 mg), those who were also consuming >1,400 mg/d in their diet had a 2.5-times higher risk of all-cause death than women with similar total intakes not taking a supplement. (83)

 

Calcium supplementation and risk of cardiovascular disease including stroke:

An analysis of 388,229 individuals aged 50 to 71 years found that high calcium intake was associated with an increased risk of cardiovascular disease (CVD) mortality in men, but not women. At study enrollment, 51% of men and 72% of women were taking some form of calcium. The study found that compared to men not taking calcium, men with calcium intake of 1000 mg/day had an elevated risk of total CVD death (20% increased risk) and heart disease death (19% increased risk) but not cerebrovascular disease. In women, there was no association between calcium supplementation and death from cardiovascular disease or cerebrovascular disease. (84)

Calcium supplements increased the risk of cardiovascular events, especially heart attacks, in older women. A re-analysis of data from the Women’s Health Initiative Calcium/Vitamin D Supplementation Study found that among the almost 16,718 women not taking personal supplements at the time of randomization, being randomized to new supplement use (1g calcium and 400 IU vitamin D daily) was associated with a statistically significant increase in risk of cardiovascular events (heart attack, stroke) ranging from 13%-22%. Among women already taking supplements at the start of the study, no such increase in events was seen. A meta-analysis of 3 placebo-controlled trials found that compared to placebo, calcium and vitamin D increased the risk of heart attack by 21%, stroke by 20%, and heart attack or stroke by 16%. (85)

 

Low calcium intake and stroke:

Patients with low calcium intakes of under 700 mg daily may reduce the risk of stroke by increasing calcium intake daily by 300 mg. Larsson SC, et al found that low to moderate calcium intakes under 700 mg daily on average showed a lower relative risk of stroke when daily calcium intake was increased by 300 mg in Asian populations (86). Calcium intakes of 700 mg or more daily in this study showed a slight increase in stroke risk (86).

 

Coenzyme Q10 and ischemic stroke:

Coenzyme Q10 may be useful in the treatment of endothelial dysfunction as well as the treatment of risk factors for stroke and coronary artery disease including hypertension and hyperlipidemia. Please see the sections on coenzyme Q10, coronary artery disease, hypertension, and hyperlipidemia in Preventive Health Advisor for further information.

 

Lycopene and stroke:

Lycopene is a red colored carotenoid phytonutrient found in tomatoes. A prospective population study on over one thousand Finnish men followed for over 12 years compared subjects with the highest quartile of serum lycopene level to those with the lowest quartile of serum lycopene level, and noted that subjects with higher levels had a 59% lower risk of ischemic stroke measured by hazard ratio (87). Lycopene at a dose of 15mg for 8 weeks was noted to reduce markers of oxidative stress, increase plasma superoxide dismutase activity, reduce lymphocyte DNA comet tail length (a measurement of DNA damage), improve endothelial function by 23%, decrease in C-reactive protein (CRP) significantly, lower systolic blood pressure, and improve markers of inflammation compared to placebo (88).

 

Allicor and risk of ischemic stroke:

Allicor, a long-acting garlic drug, reduced total cholesterol and LDL cholesterol in men (by 27.9 and 22.5 mg/dl, respectively), and also in women (by 11.4 and 10.8 mg/dl, respectively) (89). Allicor may also reduce age-related cardiovascular risk (89). It is unknown whether Allicor or garlic will impact the risk of ischemic stroke directly, but garlic is known to lower blood pressure, total cholesterol, LDL cholesterol, and triglycerides. Therefore, garlic reduces risk factors for stroke. Please see hypertension and hyperlipidemia sections of Preventive Health Advisor.

 

Kiwi fruit and stroke:

Consuming 2-3 kiwi fruit per day for 28 days lowered blood triglycerides levels by 15%, and reduced platelet aggregation (90). It is unknown how kiwi fruit intake alone is able to impact the risk of stroke, but fruit and vegetable intake is associated with lower stroke risk (26,20), and is part of the dietary recommendations by the American Heart Association.

 

Vitamin C and stroke:

Vitamin C levels, cardiovascular disease, and stroke:

In over 20,000 men and women age 40-79, it was found by calculation of relative risk that the highest quartiles of plasma vitamin C levels had a 42% lower risk of stroke than the lowest quartile of plasma vitamin C levels (91). Chen, GC et al performed a meta-analysis, and found 11 studies that showed a higher vitamin C intake compared to a lower vitamin C intake was associated with a lower risk of stroke (92).

 

Vitamin C levels, risk of cardiovascular disease, and mortality:

An analysis was conducted on 19,496 men and women, ages 45 to 79, in the U.K. The participants’ blood was tested for ascorbic acid (a form of vitamin C) and they were placed in five groups (quintiles) according to their serum ascorbic acid levels. Men and women were tracked separately. The researchers observed how many people died of cardiovascular disease, ischemic heart disease, cancer, and all causes in each of the blood ascorbic acid quintiles. In every case (except for women at risk of cancer), death rates were significantly lower among those with higher blood ascorbic acid levels. Those with the highest ascorbic acid levels compared to the lowest levels had half the risk of dying from ischemic heart disease, cardiovascular disease, and all causes combined. Additionally, a 20 micromol/L increase in blood ascorbic acid concentration, the same as a 50 g per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality. (73)

Vitamin C has been shown to be beneficial for people with certain diseases or conditions. High intakes of vitamin C have been associated with a decreased risk of heart disease, cancer, eye diseases, and neurological conditions. High dose vitamin C, with an upper tolerable level set at 2g, has been shown to be safe in adults. Among healthy individuals, the recommended daily intake of vitamin C is 75 mg for women and 90g for men. (93)

 

Rehabilitation post ischemic stroke:

Patients should be evaluated and treated with physical, occupational, and speech therapy as indicated based on loss of function as soon as it is safe from a medical perspective. Early rehabilitation rather than a delay will allow a better chance for recovery. In some cases, a full recovery without residual deficits from stroke will be possible. All patients who are medically stabilized following stroke should participate in inpatient rehabilitation for at least 1 month (95). If stroke deficits are less severe or the patient does not qualify for an inpatient facility, outpatient clinic treatment should be instituted. Outpatient rehabilitation should be continued after the inpatient treatment outcome is maximized. A patient that is severely debilitated following stroke may not tolerate the duration and intensity of activity required for inpatient rehabilitation and therefore, subacute rehab as part of short term nursing home care may be the next best option.

 

Inpatient rehabilitation following stroke:

Within a retrospective study, it was found that early physical, occupational, and speech therapy post-stroke treatment resulted in significant improvement of both the Barthel Index (a reliable scoring system used to measure functional independence during activities of daily living) and the Functional Independence Measure (a score placed on the degree of independence noted before and after rehab). The study found that inpatient rehab stays over 1 month did not seem to add additional functional independence after the first month. Also, older patients were noted to have a lower functional independence both before and after rehab compared to younger patients. (95)

 

Improvement of motor function with outpatient rehabilitation after stroke:

The Barthel Index (a reliable scoring system used to measure functional independence during activities of daily living) was found to have a statistically significant improvement from an average of 57 on admission to 79 at 3 months after discharge from an outpatient rehab clinic (96)

 

Aerobic exercise following stroke:

According to Boss HM et al, there has been no formal cardiopulmonary exercise treatment offered for secondary prevention of stroke despite its effectiveness for coronary artery disease. In the study, patients who had a minor stroke or transient ischemic attack and underwent exercise testing plus an exercise program, did not develop any cardiovascular events. Also, more of the patients who exercised reached medical treatment goals than those who did not exercise. Patients who are not contraindicated to undergo cardiopulmonary exercise due to cardiovascular or lung disease may benefit from this as a secondary prevention method. (97)

 

 

Assessment and Plan: Ischemic Stroke, Brain Attack

• Atherosclerosis was described by a world renowned Cardiologist, William C. Roberts, MD as the leading cause of heart attacks, stroke, and peripheral vascular disease. This author enforced that cholesterol intake causes atherosclerosis. (1)

 

• Risk factor modifications to prevent or improve coronary heart disease may also reduce the risk of stroke.

 

• For further information on weight loss, hyperlipidemia, hypertension, diabetes mellitus, aerobic exercise, resistance training, or smoking cessation, please see these individual sections in Preventive Health Advisor.

 

• According to the American Heart Association (AHA) Scientific Statement, Diet and Lifestyle Recommendations: Revision 2006 by Lichtenstein, AH et al, the key to the prevention of coronary heart disease (CHD) or improvement of the CHD course is the emphasis of the following goals for cardiovascular disease risk reduction (3):

 

• Diet recommendations by the AHA:
  • Eat a healthful diet the majority of the time including vegetables, fruits, whole grains, fat-free or low fat dairy, beans, lean meat, poultry, and oily fish at least twice weekly. Limit total cholesterol to 300 mg per day for healthy adults and for patients with LDL cholesterol under 100 mg/dl. Limit cholesterol to 200 mg per day for patients with coronary artery disease.
  • Total fat intake limited to under 25–35 percent of total calories per day.
  • Saturated fat intake limited to under 7 percent of total calories per day.
  • Trans fat intake should be under 1 percent of total calories per day.
  • Other fat in the diet should come from monounsaturated or polyunsaturated oils from unsalted nuts, seeds, oily fish, and vegetable oil such as canola or olive oil.

 

• Maintain a healthy bodyweight: Maintain a healthy bodyweight with a body mass index (BMI) between 18.5-24.9 kg/m².
  • Using hazard ratios, Saito, I et al found that the following BMI levels were paired with a higher risk of stroke in men and women compared to a BMI of 23.0-24.9 kg/m² (4):
  • BMI of 27.0-29.9 kg/m² was associated with a 9% higher risk of stroke in men and a 29% higher risk in women.
  • BMI of over 30.0 kg/m² was associated with a 25% higher risk of stroke in men and more than double the risk of stroke in women.
  • The AHA defines overweight as 25-29.9 kg/m², and obesity as greater than or equal to 30 kg/m². BMI can be calculated from the basic formula: [Weight (lb) / (Inches of height)²] x 703. BMI may also be calculated using a commonly available BMI calculator such as that available here: http://www.nhlbi.nih.gov/guidelines/obesity/BMI/bmicalc.htm from the NIH National Heart, Lung and Blood Institute.

 

• The lipid profile should be monitored by the primary care physician who should work with the patient to achieve LDL, HDL, triglyceride and total cholesterol goals. The Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol has established that the following lipid profile is optimal (as cited in Lichtenstein, 2006):
  • LDL optimal under 100 mg/dl, near optimal 100-129 mg/dL, borderline high 130-159 mg/dL, high 160-189 mg/dL, and very high over 190 mg/dL.
  • Total cholesterol is recommended to be under 200 mg/dL.
  • No specific goals for HDL and triglycerides exist but HDL under 40 mg/dL for men and under 50 mg/dL for women as wells as a triglyceride level of over 150 mg/dL are all associated with metabolic syndrome.

 

• Roberts view of lipid profile goals are more strict than the AHA and recommends the following (1):
  • LDL cholesterol needs to be <100 mg/dL and ideally <70 mg/dL.
  • Total cholesterol should be <150 mg/dL, and the high-density lipoprotein (HDL) cholesterol >20 mg/dL.
  • The low HDL goal is rationalized by the author that levels below 20 are not dangerous if LDL and total cholesterol is also low.

 

• Blood pressure:
  • Focus on achieving normal blood pressure.
  • According to the AHA, the lifetime risk of hypertension is about 90% and any elevation above a normal blood pressure of 120 systolic over 80 diastolic increases risk of coronary heart disease even if elevated into pre-hypertensive levels.

 

• Blood glucose levels:
  • Keep blood glucose in normal range:
  • According to the AHA, normal fasting blood glucose is less than or equal to 100 mg/dL and a fasting blood glucose of of greater than or equal to 126 is diagnostic of diabetes.
  • Weight loss, exercise, and avoidance of concentrated sweets can greatly improve control of glucose and insulin resistance.

 

• Exercise goals:
  • Maintain a physically active lifestyle as regular activity promotes cardiovascular fitness.

 

• Smoking: Patients should be counseled to quit smoking. Patients should be counseled to quit smoking at every clinic appointment. If they don’t smoke, they should be counseled not to start. A combination of several methods should be used to assist in cessation. For instance, combine nicotine replacement with at least one additional method such as an exercise program, medication, hypnosis, electronic cigarettes, or formal counseling such as support groups. The recommendation to counsel patients to stop smoking, stop using tobacco products, and provide methods of cessation is reinforced by the U.S. Preventive Services Task Force. Many resources are available to assist in smoking cessation such as the online sites http://smokefree.gov/  , http://www.cdc.gov/tobacco/campaign/tips/quit-smoking/   and the phone number for free help 1-800-QUIT-NOW. Please see the section on smoking cessation in Preventive Health Advisor.

 

• The American Heart Association metrics were applied by Artero, EG et al in The Aerobics Center Longitudinal Study. The authors described that in order to reduce the risk of cardiovascular mortality over the course of 11 years by 50-60% goals must meet at least 3 out of 4 of the following (2):
  • 1) Total cholesterol lower than 200 mg/dL
  • 2) Blood pressure lower than 120/80 mm Hg
  • 3) Not having diabetes
  • 4) Free of heart disease
  • AND meet at least 2 out of 4 of the following:
  • 1) No smoking
  • 2) Normal body mass index (BMI)
  • 3) Engaging in physical activity
  • 4) Eating healthfully

 

• Importance of homocysteine levels and stroke:
  • Homocysteine levels should be monitored and treated as necessary by the primary care physician to reduce the risk of stroke.
  • Patients with elevated homocysteine levels of over 18 micromoles per liter (7), may be considered for daily combination regimen of 2.5 mg of folic acid (vitamin B9), 50 mg vitamin B6 and 1mg of vitamin B12 (8).
  • Some studies suggest that folic acid was ineffective alone for preventing stroke unless combined with vitamin B12 and vitamin B6 (12,9), and the greatest benefit was seen in patients compliant with the regimen of 3 vitamins for over 3 years (8).
  • Patients who will likely benefit the most in treatment for an elevated homocysteine level include adults younger than age 69, those with hyperlipidemia, patients from areas where folic acid-fortified food is not available, and patients not currently taking anti-platelet drugs or cholesterol-lowering drugs (8).
  • Alternatively, patients with elevated homocysteine should seek food sources containing similar amounts to the recommended doses of folic acid, vitamin B6, and vitamin B12 daily from their diet. Of note, vegetarians especially without dairy intake will need to take an oral vitamin B12 supplement. One serving of milk can provide about half of the vitamin B12 daily allowance, but higher doses are used to lower homocysteine.

 

• Evidence-based diet and exercise combination programs for coronary artery disease:
  • The Pritikin Program evidence-based benefits after 12-15 days (14,15,16):
    • Body mass index, 3% reduction
    • Blood pressure, glucose and LDL, all with 10%-15% reduction
    • Triglycerides, 36% reduction
    • Slowed or reversed progression of coronary heart disease and reduce the need for coronary artery bypass grafts (CABG), rates of angioplasty procedures and percutaneous interventions.
    • Usually program is done for 3-4 weeks allowing additional benefit.
  • Pritikin Program includes (13,14,15):
    • Very low fat, less than 10% of calories.
    • Low sodium and avoid salty foods.
    • High fiber with at least five ½-cup servings of whole grains daily (wheat, oats, and brown rice or starch vegetables such as potatoes, and dried beans and peas.
    • Refined grain products (white flour, regular pasta, white rice) are limited to two servings daily.
    • At least four 1-cup servings of raw vegetables daily or ½-cup servings of cooked vegetables. Dark green, leafy, and orange or yellow vegetables are preferred
    • At least three servings of fruit, one of which can be fruit juice.
    • Two servings daily of calcium-rich foods such as nonfat milk, nonfat yogurt or fortified and enriched soymilk.
    • No more than one caffeinated drinks daily. Instead drink water, low-sodium vegetable juices, grain-based coffee substitutes or caffeine-free teas.
    • No more than four alcoholic drinks per week for women and no more than seven for men, with red wine preferred over beer or distilled spirits.
    • No more than seven egg whites per week.
    • No more than 2 ounces (about 1/4 cup of nuts) daily.
    • Moderate amounts of fish, nonfat dairy, and lean meat with no more than one 3.5 cooked serving of animal protein per day with fish and shellfish are preferred. Lean poultry should optimally be limited to once a week and lean beef to once a month.
    • Adapted to vegetarians by replacing animal protein with protein from soy products, beans, or lentils.
    • Avoid fried foods, dressing with fat, and fatty sauces, animal fats, processed meat, dairy products not made with non-rat milk, egg yolks, salty snacks, cakes, cookies, and similar high-calorie choices.
    • Eat frequently with three meals a day plus two snacks.
    • Artificial sweeteners such as Splenda are okay.
    • 45 minutes of moderate exercise daily such as walking.
    • Medicare may approve coverage for qualifying individuals with a history or risk of cardiovascular events. The program has been approved for coverage under Part B of Medicare. Medicare will reimburse eligible beneficiaries for up to 72 one-hour ICR sessions, up to 6 sessions per day, at the Pritikin Longevity Center & Spa.
  • The Dean Ornish Program for Reversing Heart Disease evidence-based benefits (16):
    • Weight loss of 13.3 pounds in the first 12 weeks and 15.9 pounds after 1 year.
    • Significant reductions in systolic blood pressure (BP), diastolic BP, total cholesterol, triglycerides, and LDL-cholesterol after 12 weeks were still significant after 1 year.
    • Exercise capacity increased by 18% after 12 weeks and 24% after one year.
    • Reductions in depression were still significant after 1 year.
    • Hemoglobin A1C in diabetics continued to decrease after one year.
    • Improvement in severity of angina after 1 year.
  • Ornish Program includes (16):
    • Plant-based, meatless diet, meditation, and regular exercise with adherence to the program between 85 to 90% after one year in hospitals and clinics that have offered it.
    • Medicare Part B covers The Dean Ornish Program for Reversing Heart Disease, under Intensive Cardiac Rehabilitation (ICR). Eligibility includes acute myocardial infarction within the preceding 12 months, a coronary artery bypass surgery, current stable angina pectoris, heart valve repair or replacement, percutaneous transluminal coronary angioplasty or coronary stenting, a heart or heart-lung transplant, or other cardiac conditions as specified through a national coverage determination. (16)

 

• Vegetarian diet and stroke according to Huang. T et al (26):
  • All-cause mortality, mortality from circulatory diseases, and mortality from cerebrovascular diseases in vegetarians was lower when compared to non-vegetarians by 9%, 16%, and 12%, respectively.
  • Vegetarians had a statistically reduced rate of ischemic heart disease mortality by 29% and reduced cancer incidence by 18%.

 

• The Therapeutic Lifestyle Changes Diet (17,18):
  • Saturated fat below 7% of the total calories.
  • Total fat intake 25-35% of daily total calories.
  • Cholesterol intake below 200 milligrams each day.
  • Sodium intake under 2400 mg per day.
  • Calorie intake should be kept to a level needed for maintaining healthy weight but reduce blood cholesterol level.

 

• Effect of adding 30 minutes of daily exercise at 50-75% of age-predicted maximum heart rate, to a Therapeutic Lifestyle Changes Diet (TLC) in 6 months (17):
  • Assisted 89% of participants to reach an LDL cholesterol goal of under 130 mg/dL without lowering HDL levels or needing to add or increase lipid lowering therapy.
  • Mean total cholesterol, LDL cholesterol and triglycerides decreased by 9.2% (p=0.08), 9.3% (p<0.018), and 18.8% (p<0.05), on average respectively.
  • HDL cholesterol increased 2.6% on average (p=0.41).
  • Women: 12.3% reduction in LDL cholesterol and an 11.4% increase in HDL cholesterol
  • Men: 7.9% reduction in LDL cholesterol and no change in HDL
  • Systolic and diastolic blood pressure (BP) decreased 9% (p<0.001) and 13%, respectively (p <0.0001).
  • BP reductions were two-fold greater than in the Diet and Systolic Hypertension study (DASH).
  • 50% reduction in angina.

 

• Mediterranean diet and cardiovascular diseases (19): A Mediterranean style diet generally consists of:
  • Fruits, vegetables, whole grains, olive oil, legumes, nuts, beans, herbs, seeds, and spices as the primary basis for each meal.
  • Fish and seafood is eaten often at least twice per week.
  • Yogurt, poultry, eggs, and cheese is consumed in moderate portions daily to weekly.
  • Meats and sweets are eaten infrequently.

 

• Hoevenaar-Blom, MP et al found that patients on a Mediterranean diet for 10-15 years had (20):
  • 12% lower risk of stroke but transient ischemic attacks were not reduced or increased.
  • 14% lower risk of myocardial infarction.
  • 22% lower risk of fatal cardiovascular diseases.
  • 26% lower risk of coronary artery disease.
  • Risk of total amount of cardiovascular diseases was not reduced much.
  • A review of research by Foroughi, M et al on stroke and nutrition found that a Mediterranean style diet or DASH (dietary approaches to stop hypertension) diet may reduce ischemic stroke incidence (21). Please see the section on hypertension to review the DASH diet.

 

• Nut consumption and risk of stroke:
  • Consumption of almonds and walnuts lowers total and LDL cholesterol based on their fatty acid profile and other bioactive compounds with cholesterol-lowering properties. (22).
  • Few studies exist on the association of nut consumption with the risk of stroke and more research needs to be performed.
  • One epidemiological study showed no association between nut intake and ischemic stroke, but noted instead that there may be an association of nut intake with hemorrhagic stroke (23).

 

• Fiber intake and cardiovascular disease: Fiber intake is associated with a lower risk of cardiovascular disease including both ischemic stroke and ischemic heart disease. A meta-analysis of cohort studies found that an increase in total fiber intake of 7 grams per day was associated with a 7% lower risk of stroke (24).

 

• Whole grains and cardiovascular disease: Whole grain intake (average 2.5 servings per day vs. 0.2 servings per day) was associated with a 21% lower risk of CVD events (27).

 

• Antioxidants for prevention of cardiovascular disease:
  • For the prevention of cancer or cardiovascular disease, the U.S. Preventive Services Task Force (USPSTF) recommends against the use of beta-carotene supplements, alone or in combination. According to the USPSTF, there is insufficient evidence to recommend for or against the use of vitamins A, C, or E supplements or multivitamins with folic acid or antioxidant combinations for the prevention of cancer or cardiovascular disease. (28)
  • Beta carotene and cardiovascular disease: There is some evidence that suggests fruit and vegetable based beta-carotene is associated with lower risk of cardiovascular disease.
  • Beta carotene intake in the form of vegetables was associated with a lower risk of cardiovascular and cancer mortality and with a lower risk for death from all causes (29).
  • For more information, please see beta-carotene section of Preventive Health Advisor.

 

• Vitamin D, stroke, cardiovascular mortality and all-cause mortality: For more information, please see vitamin D section of Preventive Health Advisor.
  • Maintain favorable levels of vitamin D in all patients with any risk factors for cardiovascular disease. Vitamin D is not established as a direct cause of cardiovascular disease, but vitamin D deficiency is associated with a higher incidence of hypertension, hyperlipidemia, coronary artery disease, stroke, chronic kidney disease, and diabetes mellitus type 2 (30). A retrospective analysis showed that patients with diabetes mellitus have a very low 25-hydroxy vitamin D level, and also found that high levels of triglycerides, LDL cholesterol, and HbA1C had a consistent association with vitamin D deficiency in type 2 diabetes patients (35).

 

• Vitamin D levels, cardiovascular-related mortality, and all-cause mortality:
  • Michaëlsson K et al found that a vitamin D concentration of 24 to 34 ng/ml (60 to 85 nmol/L) approximately translates to a vitamin D dose of 2000 IU/d and corresponded to the lowest cardiovascular-related and all-cause mortality (32).
  • Overall mortality was increased by 50–60% among subjects in the lowest 10% and highest 5% of the vitamin D level curve distribution, whereas cardiovascular mortality was increased only in the bottom 10%. Vieth reported that the ideal level of vitamin D intake for adults should be 50 mg (2000 IU) per day (33).
  • Bosomworth NJ conducted a review of multiple studies, and determined that 500-1500 IU/d of vitamin D reduced all-cause mortality (34).
  • After Sun Q, et al followed 74,272 women and 44,592 men over 20 years, 9,886 cases of coronary heart disease and stroke occurred, and a 16% reduction in heart disease was seen among men with an intake of 600 IU or more per day of vitamin D, compared with those with an intake of 100 IU (31).

 

• Red wine and cardiovascular disease: Moderate red wine consumption has been associated with the following benefits (37):
  • Decreased cardiovascular risk
  • Reduced mortality
  • Improved cholesterol profile,
  • Bone density increase in older adults
  • Reduced risk of esophageal and gastric cancer
  • Better reduction of both mortality risk and risk of cardiovascular disease than spirits, beer and white wine.
  • Increase in HDL cholesterol.
  • Relative risk of cardiovascular and cerebrovascular mortality was significantly less for those who had a low to moderate intake of wine, but beer intake did not change mortality risk much and drinking spirits increased mortality (98).
  • At the end of a 4-week study period, results showed that drinking red wine in moderation increased HDL cholesterol by 11–16%, decreased fibrinogen by 8–15% and according to the authors was associated with beneficial changes in blood lipids and fibrinogen that may help to reduce the risk of cardiovascular disease (38).
  • De Gaetano and Cerletti reported that after red wine consumption (30 g alcohol daily for 4 weeks) as compared to the same amount of alcohol given as spirit such as vodka, whiskey, gin, tequila, or rum resulted in a significant increase in HDL cholesterol levels and a decreased oxidation of LDL cholesterol. The authors reviewed a meta-analysis which indicated a significant negative relationship between moderate wine drinking of 150-300 ml daily and the risk of cardiovascular events. In conclusion, moderate wine consumption is linked with prevention of cardiovascular disease. (39)
  • 400 mL/day of red wine for 6 weeks significantly decreased LDL cholesterol concentrations by 8% and increased HDL cholesterol concentrations by 17% and reduced cardiovascular disease risk compared to no effect for placebo (40).
  • Drinking red wine has significantly better cardiovascular disease risk reduction compared to beer, vodka, whiskey, gin, tequila, or rum (39).

 

• Drinking alcohol and cardiovascular disease:
  • Drinking alcohol in light to moderate amounts 3–4 or 5–7 days per week has been associated with a decreased risk of cardiovascular disease by about 25% and lower risk of myocardial infarction compared with men who consumed alcohol less than once per week (41).
  • Beer intake did not change mortality risk much and drinking spirits increased mortality (98).

 

• Chocolate consumption and risk of stroke:
  • Consumption of chocolate has been found to significantly reduce the risk of both ischemic stroke and hemorrhagic stroke in a large cohort study on women who ate a median of 66.5 grams per week of chocolate (42).
  • In a large cohort study on men, a median intake of 62.9 grams of chocolate per week was associated with a decrease in risk of stroke by about 17% (43).
  • Chocolate has also been noted to decrease the risk of coronary heart disease in subjects compared to others who did not consume chocolate (44).
  •  Cocoa is believed to improve blood flow by counteracting endothelial dysfunction by the action of flavonols which naturally occur in cocoa and possess antioxidant characteristics (45).
  • According to James J. E., caffeine, through its daily consumption from a variety of sources (coffee, teas, soft drinks, chocolate and medicines), may have an impact on cardiovascular risk. By typically increasing resting blood pressure (BP) in adults by about 4/2 mmHg which according to the author, could be responsible for premature deaths of about 14% for coronary heart disease and 20% for stroke. (47)

 

• Green tea and cardiovascular disease (CVD) population study according to Kuriyama, S et al of “The Ohsaki Study” (50):
  • Researchers followed 40,530 Japanese adults up to 11 years.
  • Women who drank ≥ 5 cups/day of green tea had a 31% lower risk of dying from CVD and a 23% lower risk of mortality from all causes than women who drank <1 cup/day.
  • Women who drank 1 to 2 cups/day or 3 to 4 cups/day green tea had a 16% and 31% reduced risk of CVD, respectively.
  • Those who drank 1 to 2 cups/day or 3 to 4 cups/day green tea had a 2% and 18% reduced risk of all-cause mortality, respectively.
  • The protective effect of green tea was stronger in women than in men.
  • In men who drank ≥ 5 cups/day green tea their all-cause mortality risk fell by 12%.
  • Men who drank 1 to 2 cups/day or 3 to 4 cups/day green tea had a 7% and 5% reduced risk of all cause-mortality, respectively.

 

• Coffee, green tea, black tea, oolong tea consumption and cardiovascular disease risk (46):
  • Compared with non-tea drinkers, women consuming green tea at 1-6 cups/week, 1-2 cups/day, 3-5 cups/day and ≥ 6 cups/day had a 66%, 72%, 61%, and 58% reduced risk of coronary heart disease compared to non-tea drinkers.
  • Men drinking ≥ 1 cups/day of oolong tea benefited from a 61% reduced risk of CVD.
  • Individuals in the second highest quintile of total caffeine intake had a total CVD risk reduction of 38% in men and 22% in women.

 

• Aerobic exercise to help prevent stroke: For more information, please see the aerobic exercise section in Preventive Health Advisor. Epidemiological research shows that risk of death from both stroke and cardiac mortality is doubled to tripled in sedentary people compared to those who undergo regular physical activity (74).

 

• Aerobic exercise benefits: Individuals of all ages capable of aerobic exercise should do so most days of the week for the following benefits: heart and lung conditioning, improved pumping efficiency of the heart, improved circulatory system (53), weight control and less obesity (54), cholesterol reduction (54,55), triglyceride lowering (54), lowering of blood pressure (56), lower rate of smoking (57), control of diabetes (58,59), lower cardiac mortality (57), and reduced all-cause mortality (57).

 

• Benefits of aerobic exercise, 1 hour per day, 5 days per week, over 10 years (54):
  • With exercise alone: Decrease body mass index about 11.5 kg/m^2, reduce total cholesterol by about 11 points, and reduce their triglycerides by about 105 mg/dl.
  • With exercise plus low fat, high fiber, complex carbohydrate diet: Decrease in body mass index about 16.5 kg/m^2, lower total cholesterol about 33 points, reduction of LDL about 20 points, and reduction of triglycerides about 109 mg/dl.
  • Aerobic exercise done along with or without a cardiac rehab program reduces cardiac and all-cause mortality in coronary artery disease.

 

• Starting exercise in apparently healthy adults: According to the American College of Sports Medicine (ACSM) and the American Heart Association (AHA), older adults need moderate-intensity (between 5-6 on a 10-point scale) aerobic endurance activity for a minimum of 30 min which can be achieved in short 10 minute sessions on five days each week or vigorous-intensity aerobic, (rated a 7-8 on a 10-point scale) activity for a minimum of 20 min on 3 days each week.

 

• Amount of activity according to the World Health Organization (60):
  • The most benefit from physical activity is achieved with at least 2.5 hours of aerobic exercise of moderate intensity per week, which can be accumulated in 10-minute periods.
  • At least 2 days/week vigorous intensity aerobic exercise and resistance exercises for muscle strengthening are recommended.
  • Increased intensity, frequency and duration of exercise is associated with increased added health benefits.

 

• American College of Sports Medicine (ACSM) Cardiorespiratory Training Guidelines:
  • Main components of an exercise session per ACSM include warm-up, conditioning stimulus, and cool down. Warm-up before the session and cool down after the session of exercise consists of 5-15 minutes of activity at 50% training intensity of the conditioning stimulus.
  • Guide aerobic exercise training for patients according to ACSM guidance by calculating training intensity, then proceed through training progression according to the initial, improvement, and maintenance stages.

 

• Power walking: This exercise is generally an effective initial aerobic activity for beginners. Start walking at a normal pace and continue to increase the walking speed over 10 minutes to reach a heart rate of 110 – 120 beats per minute resulting in mild perspiration. Then continue to follow the ACSM guidelines.

 

• Starting exercise in chronically ill patients: A respected credible source available for exercise prescription is Thompson et al, American College of Sports Medicine’s (ACSM’s) Guidelines for Exercise Testing and Prescription (52).

 

• Risk of exercise exceeds the benefits in the following medical conditions (52):
  • Recent myocardial infarction, unstable angina, ventricular arrhythmias, aortic dissection, aortic aneurysm, congestive heart failure, severe aortic stenosis, inflammation of the heart muscle or pericardium, pericarditis, pulmonary embolism, intracardiac thrombi, blockage of the main artery of the lung or one of its branches, and acute infection.

 

• The following medical conditions may increase the risk of complications during exercise: (52): Untreated or uncontrolled high blood pressure, moderate aortic stenosis, severe narrowing of the left ventricle of the heart just below the aortic valve, mitral stenosis, atrial arrythmias, swelling of a blood vessel in the heart that occurs after a heart attack, ventricular bigeminy or trigeminy, frequent premature ventricular contractions, deterioration of the heart muscle, metabolic disease (diabetes, thyroid disease, etc) or electrolyte abnormality, chronic or recurrent infectious disease such as malaria and hepatitis, neuromuscular, musculoskeletal or rheumatoid diseases made worse by exercise, or complicated pregnancy. For these conditions, the physician should refer to the ACSM’s guidelines for exercise testing and prescription.

 

• For the following topics, please see the aerobic exercise section in Preventive Health Advisor:
  • Exercise cardiac stress testing referral
  • Clinical cardiopulmonary exercise testing
  • Medication effects during exercise

 

• Aspirin and stroke prevention: Aspirin for prevention of cardiovascular disease and stroke according to the U.S. Preventive Services Task Force (USPSTF) (63):
  • Ideal dose of aspirin: According to the USPSTF, the ideal dose of aspirin is not known, but a dose of 75 mg per day appears as effective as higher doses and may have less risk of gastrointestinal bleeding.
  • Men younger than 45 years: For myocardial infarction prevention in men younger than 45 years the USPSTF recommends against the use of aspirin since the benefit for prevention of cardiovascular events is small.
  • Men age 45 to 79 years: The USPSTF strongly recommends the use of aspirin when the potential benefit due to a reduction in myocardial infarction is more beneficial than the potential harm due to gastrointestinal hemorrhage.
  • Men and Women 80 years of age and older: According to the USPSTF, there is insufficient evidence to determine the risk verses benefit of taking aspirin by men and women over 79 years of age for the prevention of cardiovascular disease.
  • Women are not believed to benefit from aspirin for heart disease but women do benefit from aspirin in the prevention of ischemic stroke.
  • Women age 55 to 79 years: The USPSTF strongly recommends aspirin when the potential benefit due to a reduction in ischemic strokes is more beneficial than the potential harm due greater gastrointestinal hemorrhage.
  • Women 55 years old or younger: The USPSTF recommends against the use of aspirin for stroke prevention since the benefit for prevention of ischemic stroke is small.

 

• Atrial fibrillation: Patients with atrial fibrillation are at a higher risk for stroke between 1-20% per year or 4.5% on average depending on the presence of additional risk factors and medical problems. For detailed information on prevention of stroke with anticoagulation including warfarin (Coumadin), antiplatelet agents (aspirin and clopidogrel) and new recommendations for dabigatran, please see the American Heart Association/American Stroke Association (AHA/ASA) “Guidelines for the Primary Prevention of Stroke” available at http://www.ncbi.nlm.nih.gov/pubmed/22858728 or http://stroke.ahajournals.org/content/43/12/3442.full (6).

 

• Prediction of ischemic stroke: A CHADS2 score is the most accurate tool known for prediction of stroke in patients with atrial fibrillation (65). Calculating a CHADS2 score uses the following scoring system (129):
  • 2 points for previous stroke or TIA (transient ischemic attack)
  • 1 point for recent CHF (congestive heart failure)
  • 1 point for hypertension
  • 1 point for age 75 years or older
  • 1 point for diabetes

 

• Rate of stroke by CHADS2 score: The rate of stroke occurrence without anticoagulation per year depends upon the CHADS2 score as follows (65):
  • CHADS2 score of 0: 1.9% per year.
  • CHADS2 score of 1: 2.8% per year.
  • CHADS2 score of 2: 4.0% per year.
  • CHADS2 score of 3: 5.9% per year.
  • CHADS2 score of 4: 8.5% per year.
  • CHADS2 score of 5: 12.5% per year.
  • CHADS2 score of 6: 18.2% per year.

 

• Treatment for prevention of ischemic stroke in patients with atrial fibrillation: The patient’s cardiologist and primary care provider are responsible for recommending treatment for the prevention of stroke. According to the American Heart Association/American Stroke Association (AHA/ASA) basic treatment guidelines are as follows (64):
  • CHADS2 score of 0: No treatment or aspirin is recommended.
  • CHADS2 score of 1: Antithrombotic therapy choice by the physician varies.
  • CHADS2 score of 2 or higher: Anticoagulation is recommended for atrial fibrillation to prevent stroke.
  • Warfarin with dose changes to maintain therapeutic range reduced the risk of stroke in atrial fibrillation from an average of 4.5% to 1.4%.
  • Aspirin reduced the risk of stroke in atrial fibrillation by 21%.
  • Benefit verses risks of bleeding or adverse effects from anti-thrombotic therapy should be discussed in detail with the physician. The risk of severe bleeding episodes while taking warfarin was about 1.3% per year, and with aspirin, about 1% per year. Therapy with both aspirin and clopidogrel were demonstrated to be about the same bleeding risk as warfarin with a small reduction in stroke rates.

 

• Creatine phosphate and atrial fibrillation: Creatine has been shown to have lower rates of arrhythmias before and after heart surgery, but creatine phosphate has not been studied yet for use in atrial fibrillation, but should be investigated. Three days before surgery, creatine phosphate supplementation showed improved heart function after bypass surgery with less ventricular arrhythmias and reduced use of inotropic drugs (66). Creatine phosphate given during cardiac surgery and the early postoperative period reduced CK and CKMB levels plus resulted in a lower percentage of arrhythmias compared to controls (67).

 

• Omega-3 fatty acids and stroke:
  • Omega-3 fatty acids appear to have more benefits in improvement of heart disease than stroke. Many benefits of omega-3 fish oil are included below, but research is mixed showing many trials and meta-analyses with positive findings, but others lacked in showing a benefit. Also, please see the coronary artery disease section for more information.
  • American Heart Association (AHA) fish, fish oil, and oil intake (68): Omega-3 fish oil is beneficial for treatment of elevated triglycerides. Patients needing triglyceride lowering, should have fish oil prescribed by a physician. The AHA recommends a daily intake of 2-4 grams of EPA+DHA for elevated triglycerides, but a patient prescribed over 3 grams of omega-3 fish oil should be overseen by a physician due an increased risk of bleeding.
  • Omega-3 fish oil is associated with a reduction in total mortality (69,70,71), lower risk of sudden death (69,71), lower risk of nonfatal MI (70), less risk of nonfatal stroke (70), 20% reduction in deaths from cardiac causes (72), if taken within 18 hours of myocardial infarction symptoms noted a reduction in total cardiac events (73), reduction in total angina pectoris (73), reduction in cardiac arrhythmias (73), and lower risk of left ventricular enlargement (73).
  • Some studies showed no benefit for reduction in stroke (74), no decrease in nonfatal heart attacks (69), no reduction in all-cause mortality (72), no reduction in total cardiac deaths (73), and some showed no benefit in terms of arrhythmic events (72).

 

• In a randomized controlled trial called the GISSI-Prevenzione trial done in Italy, 11,324 patients with pre-existing coronary heart disease (CHD) were randomly allocated to either 300 mg vitamin E, 850 mg omega-3 fatty acid ethyl esters (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]), both, or no treatment and followed for 3.5 years noted the following results (71):
  • Reduction in nonfatal stroke was seen in participants taking 850 mg omega-3 fatty acid alone.
  • Participants taking omega-3 fatty acid after 6-months experienced a 2.5% increase in HDL cholesterol and a 4% reduction in triglycerides.

 

• Fish intake: Fish intake has been associated with a 29% reduction in mortality over 2 years when eating three fish meals a week (75). An inverse association has been noted between fish intake and coronary heart disease mortality (76).

 

• Omega-3 fish oil and atrial fibrillation: Supplementation with 1 gram of omega-3 fish oil for 1 year did not reduce the incidence of recurrent atrial fibrillation (128). Few studies have shown benefit of using omega-3 fish oil for prevention or recurrence of atrial fibrillation (72).

 

• Omega-3 fish oil adverse reactions and interactions:
  • A total of 10 studies were reviewed by Villani AM et al to determine potential serious adverse effects of fish oil at a dose of under 1.86 grams per day (78). It was found that there were no serious adverse effects reported in 994 adults over 59 years of age and other non-serious adverse effects were not significantly different from placebo (78).
  • Fish oil has been reported to affect platelet aggregation, reduce vitamin K dependent factors which may be associated with an increased anticoagulation (reduce blood clotting) effect. Consumption should be avoided when taking anticoagulants like aspirin, warfarin, or ticlopidine because of the potential increased risk of bleeding (79).
  • A case of a 67-year old woman taking warfarin (1.5 mg/day), an increase in her fish oil intake from 1 g/day to 2 g/day was associated with an increase in time for blood to clot as measured by the international normalized ratio (INR) which went from 2.8 to 4.3 within 1month, and decreased to 1.6 after the fish oil dose was reduced (80).
  • An intake of 6 grams per day of docosahexaenoic acid (DHA) found no significant difference found in blood coagulation, platelet function, or thrombotic parameters including prothrombin time, activated partial thromboplastin time, antithrombin-III levels, and platelet aggregation (81).
  • Fish oil may contain harmful contaminants such as heavy metals including mercury, dioxins, and polychlorinated biphenyls (PCBs). This risk can be reduced by purchasing fish oil that has undergone a purification process specified on the label (approved by the FDA, EPA, or US Pharmacopeia) (82)

 

• Calcium intake, cardiovascular disease, and stroke: Research shows that potential health risks occur with taking calcium supplements.
  • One large cohort study showed higher rates of death from all causes, cardiovascular disease, ischemic heart disease, but not from stroke with daily calcium intakes of over 1400 mg (83).
  • A second large cohort study showed that men with calcium intakes of 1000 mg daily had an elevated risk of total cardiovascular disease death but not cerebrovascular disease, and no increased risk was seen with calcium supplements in women (84).
  • A meta-analysis on 3 trials found 1gram of calcium and 400 IU of vitamin D to be associated with an increase in the risk of heart attack by 21%, and stroke by 20% in women (85).
  • Patients with low calcium intakes of under 700 mg daily may reduce the risk of stroke by increasing calcium intake daily by 300 mg. Larsson SC, et al found that low to moderate calcium intakes under 700 mg daily on average showed a lower relative risk of stroke when daily calcium intake was increased by 300 mg in Asian populations (86). Calcium intakes of 700 mg or more daily in this study showed a slight increase in stroke risk (86).
  • As a result, it is advisable for men and women to avoid a total daily calcium intake of over 1400 mg per day from diet and supplements due to an increased risk of cardiovascular mortality.
  • Preventive Health Advisor supports obtaining the recommended daily intake of calcium from food sources rather than supplements, but not to exceed calcium intake of over 1400 mg per day. Calcium supplements are not advised until further research clarifies these findings. Risk may outweigh the benefits especially if the amount of calcium taken in the diet is unknown.

 

• Coenzyme Q10 and ischemic stroke:
  • Coenzyme Q10 may be useful in the treatment of endothelial dysfunction as well as the treatment of risk factors for stroke and coronary artery disease including hypertension and hyperlipidemia. Please see the sections on coenzyme Q10, coronary artery disease, hypertension, and hyperlipidemia in Preventive Health Advisor for further information.

 

• Lycopene and stroke: Lycopene is a red colored carotenoid phytonutrient found in tomatoes.
  • A prospective population study on over one thousand Finnish men followed for over 12 years compared subjects with the highest quartile of serum lycopene level to those with the lowest quartile of serum lycopene level, and noted that subjects with higher levels had a 59% lower risk of ischemic stroke measured by hazard ratio (87).
  • Lycopene at a dose of 15 mg for 8 weeks was noted to reduce markers of oxidative stress, increase plasma superoxide dismutase activity, reduce lymphocyte DNA comet tail length (a measurement of DNA damage), improve endothelial function by 23%, decrease C-reactive protein (CRP) significantly, lower systolic blood pressure, and improve markers of inflammation compared to placebo (88).

 

• Garlic, Allicor, and risk of ischemic stroke: Allicor, a long-acting garlic drug, reduced total cholesterol and LDL cholesterol in men (by 27.9 and 22.5 mg/dl, respectively), and also in women (by 11.4 and 10.8 mg/dl, respectively) (89). Allicor may also reduce age-related cardiovascular risk (89). It is unknown whether Allicor or garlic will impact the risk of ischemic stroke directly, but garlic is known to lower blood pressure, total cholesterol, LDL cholesterol, and triglycerides. Therefore, garlic improves risk factors for stroke. Please see hypertension and hyperlipidemia sections of Preventive Health Advisor.

 

• Kiwi fruit and stroke: Consuming 2-3 kiwi fruit per day for 28 days lowered blood triglycerides levels by 15%, and reduced platelet aggregation (90). It is unknown how kiwi fruit intake alone is able to impact the risk of stroke, but fruit and vegetable intake is associated with lower stroke risk (26,20), and is part of the dietary recommendations by the American Heart Association.

 

• Vitamin C and stroke: High intakes of vitamin C have been associated with a decreased risk of heart disease, cancer, eye diseases, and neurological conditions. High dose vitamin C, with an upper tolerable level set at 2g, has been shown to be safe for adults. Among healthy individuals, the recommended daily intake of vitamin C by authorities is however much lower at 75 mg for women and 90g for men. (94)
  • In over 20,000 men and women age 40-79, it was found by calculation of relative risk that the highest quartiles of plasma vitamin C levels had a 42% lower risk of stroke than the lowest quartile of plasma vitamin C levels (91).
  • Chen, GC et al also found 11 studies that showed a higher vitamin C intake compared to a lower vitamin C intake was associated with a lower risk of stroke (86).
  • According to Khaw, KT et al (93):
    • 19,496 men and women, ages 45 to 79 were tested for ascorbic acid and in every case (except for women at risk of cancer), death rates were significantly lower among those with higher blood ascorbic acid levels.
    • Those with the highest ascorbic acid levels compared to the lowest levels had half the risk of dying from ischemic heart disease, cardiovascular disease, and all causes combined.
    • A 20 micromol/L increase in blood ascorbic acid concentration, the same as a 50 gram per day increase in fruit and vegetable intake, was associated with about a 20% reduction in risk of all-cause mortality.

 

 

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