Question

A recent study found that alow-risk lifestyle protected women from sudden cardiac death. Thelow-risk lifestyle was considered as  

Answer 1

We know that a healthy lifestyle is very important to prevent many chronic diseases, including heart disease, diabetes, and certain cancers. So we weren't surprised but we were impressed at how strongly associated these lifestyle factors were for preventing sudden cardiac death," says study researcher Stephanie E. Chiuve, ScD, of Brigham and Women's Hospital and Harvard Medical School, Boston.

Researchers analyzed data on lifestyle factors of 81,722 women who participated in the Nurses' Health Study from June 1984 to June 2010. Overall, there were 321 cases of sudden cardiac death among women during 26 years of follow-up. Each healthy habit conferred a lower risk of sudden cardiac disease on its own, but the risk for sudden cardiac death was lowest among women who followed all four options of the healthy lifestyle.

The Nurses' Health Study cohort was established in 1976 when 121,700 U.S. female registered nurses 30 to 55 years of age provided detailed information by questionnaire. Every two years, we send follow-up questionnaires to update our information on potential risk factors and to identify newly diagnosed cases of various diseases.

ASCERTAINMENT OF RISK AND PREVENTIVE FACTORS

The 1976 questionnaire inquired about the nurses' height and weight and about myocardial infarction in a parent before the age of 60 years. Each follow-up questionnaire asked for updated information on weight for calculation of the body-mass index (the weight in kilograms divided by the square of the height in meters) as a measure of obesity. Each questionnaire also inquired about cigarette smoking (including past smoking and the number of cigarettes smoked per day for current smokers), menopausal status (including the use of postmenopausal hormones), and physician-diagnosed hypertension and high cholesterol levels; self-reports of these diagnoses were quite accurate as compared with medical records.

Information on physical activity was first obtained in 1980 and was updated in 1982, 1986, 1988, and 1992 with a previously validated questionnaire on the frequency of activity. We estimated the amount of time per week spent in moderate-to-vigorous activities requiring 3 or more MET per hour; this excluded walking at an easy or normal pace but included brisk walking at 5 km (3 mi) or more per hour.

In 1980 we assessed diet with a 61-item food-frequency questionnaire. In 1984 the questionnaire was expanded to 116 food items, and similar questionnaires were used to update information on diet in 1986 and 1990. The questionnaires also assessed the intake of multivitamin and single-vitamin supplements. The reproducibility and validity of the food-frequency questionnaires are high when compared with multiple one-week diet records and a variety of biochemical markers, as described in detail elsewhere.

To calculate the intake of specific nutrients, we specified a common unit or portion size for each food on the questionnaire and asked the participant how often, on average, she had consumed that amount during the previous year. The nine response categories ranged from “never” to “six or more times per day.” The intake of nutrients was computed by multiplying the frequency of consumption of each unit of food by its nutrient content. Beer, wine, and liquor were included in each of the food-frequency questionnaires to permit calculation of alcohol intake.

DEFINITION OF LOW-RISK GROUPS

Our aim in this analysis was to estimate the effect of diet and lifestyle on the risk of coronary heart disease. Therefore, we did not consider the additional effect of pharmacologic agents, including aspirin or postmenopausal hormones, or medical conditions, such as hypertension and high cholesterol levels. However, all analyses were adjusted for those factors. We sought to limit the number of lifestyle and dietary variables, and we included only those with reasonable evidence supporting their effect on coronary heart disease while recognizing that most such variables have never been tested in randomized trials.

For smoking, the low-risk group was defined as those who had stopped smoking or had never smoked. Cigarette smoking is a major risk factor for coronary heart disease and stroke. The risk declines after the cessation of smoking and approximate the level of those who have never smoked after 10 to 14 years.

Moderate alcohol consumption is associated with a lower risk of coronary heart disease and ischemic stroke but can raise the risk of hemorrhagic stroke. We considered women as being at low risk if they consumed an average of 5 g or more per day (a typical glass of wine has 11 g of alcohol). For simplicity, and because so few women in this cohort drank heavily (1.2 percent reported drinking more than 45 g of alcohol per day), we did not define an upper limit for alcohol consumption, although clearly this would be necessary in establishing public health guidelines.

For physical activity, we considered subjects to be at low risk if they engaged in an average of at least one half-hour per day of vigorous or moderate activity, including brisk walking. This cutoff point is consistent with various guidelines. We have found that this level of activity is associated with a substantial reduction in the risk of coronary heart disease and stroke (unpublished data).

Women with a body-mass index of less than 25, the standard cutoff point for overweight, were considered to be at low risk. We have previously found a significantly higher risk of coronary heart disease among women with a body-mass index of 23 to 24.9, as compared with women with a body-mass index of less than 21. The cutoff point of 25 represents a higher-than-optimal level.

We considered subjects to be at low risk if they scored in the highest 40 percent of the cohort on a composite measure based on a diet low in trans fat and glycemic load (which reflects the extent to which diet raises blood glucose levels), high in cereal fiber, marine n–3 fatty acids, and folate, and with a high ratio of polyunsaturated to saturated fat. For each of these six dietary factors, we calculated the distribution according to quintiles within the cohort and assigned each woman a score of 1 to 5 corresponding to the quintile of intake, with 5 representing the most favorable quintile. The cutoff points for the most favorable quintile for each dietary factor were as follows: less than 1.56 percent of the energy supplied by trans fat, a ratio of polyunsaturated to saturated fat of more than 0.43, consumption of more than 4.2 g of cereal fiber per day, a glycemic load of fewer than 723 units per day, more than 0.1 percent of energy from marine n–3 fatty acids, and consumption of more than 525 μg of folate per day. For each participant, the quintile value for each nutrient was summed (with a higher score representing a lower risk), and the participants with dietary scores in the highest 40 percent were defined as the low-risk group with respect to diet. We and others have previously demonstrated the importance of each of these factors for the risk of coronary disease.

POPULATION FOR ANALYSIS

We excluded women who left 10 or more items blank on the 1980 diet questionnaire, those with implausibly low or high scores for total food or energy intake (below 500 or above 3500 kcal per day), and those with previously diagnosed cancer, angina, myocardial infarction, stroke, or other cardiovascular diseases. We did not exclude women who reported high cholesterol levels or hypertension. Because diabetes increases the risk of coronary heart disease and can induce changes in diet and lifestyle, we excluded women who had diabetes at base line. Women given a diagnosis of diabetes during follow-up were included, but we used only the dietary information collected before the diagnosis. The final 1980 base-line population consisted of 84,129 women.

ASCERTAINMENT OF ENDPOINTS

We tried to review medical records for all reports of major coronary events (nonfatal myocardial infarction or death due to coronary heart disease) that occurred between the return of the 1980 questionnaire and June 1, 1994. The records were reviewed by study physicians who had no knowledge of the subjects' self-reported risk factors. Myocardial infarction was confirmed according to World Health Organization criteria, as follows: symptoms plus either diagnostic electrocardiographic changes or elevated cardiac enzyme levels. Infarctions that required hospital admission and for which confirmatory information was obtained, but for which no medical records were available, were designated as probable (these amounted to 17 percent of all infarctions). We included all confirmed and probable cases. Deaths were identified from state vital records and the National Death Index or were reported by the subject's family or postal authorities. Information on the cause of death was available for more than 98 percent of deaths.

Confirmed deaths from coronary heart disease were defined as those caused by myocardial infarction according to hospital records or autopsy, or those for which coronary heart disease was listed as the cause of death and evidence of previous coronary disease was available. In addition to confirmed deaths from coronary heart disease, we included the deaths in which coronary heart disease was listed as the underlying cause but no records were available (15 percent of all deaths from coronary heart disease). We also included sudden deaths with no plausible cause other than coronary heart disease (12 percent of deaths from coronary heart disease). Analyses limited to confirmed cases yielded similar results, although with less precision.

Strokes were considered confirmed if they met the criteria of the National Survey of Stroke. We excluded subdural hematomas and strokes caused by infection or neoplasia. Nonfatal strokes for which medical records were unavailable were defined as probable strokes and included in the analysis if they required hospitalization and were corroborated by letter or interview. Fatal strokes were confirmed by review of autopsy records, hospital records, or death certificates listing stroke as the underlying cause. In secondary analyses, strokes were added to coronary events to form the broader endpoint of cardiovascular events.

simultaneously examining the effect of several lifestyle variables, we took into account the clustering of healthful types of behavior within individual women. In addition, we adjusted for many coronary risk factors. Nevertheless, confounding by other variables, particularly socioeconomic status, could have affected our results. However, all the participants were registered nurses with some college education. Analysis of home addresses according to census-tract data found substantial economic homogeneity (Laden F: personal communication). Furthermore, adjustment for parental occupation and the husband's education had little effect on the findings. Indeed, at least some of the health benefits of higher socioeconomic status are mediated through the lifestyle variables we studied.