Cardiovascular Disease (CVD) and Mortality: Population Studies

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Numerous population (epidemiological) and controlled interventional (treatment) trials have supported highly beneficial effects of DHA/EPA from fish and fish oils in decreasing cardiovascular disease, cardiac mortality, and the favorable modification of numerous risk factors for cardiovascular disease (CVD) independent of blood cholesterol-lowering. Since the potential benefits of LNA (omega-3) from plant and vegetable oil sources with respect to cardiovascular disease has been covered extensively in Section I dealing with LNA, the present discussion in Section III will focus on DHA/EPA.

Cardiovascular disease is responsible for approximately 50% of all mortality in North America . By the age of 60, approximately 50% of the population has some form of clinical or pre-clinical cardiovascular disorder including various stages of atherosclerosis. Death rates from coronary heart disease in North America are markedly higher than corresponding rates in Japan despite only moderately higher levels of blood cholesterol in the North American population. Thus, much of the dramatic difference in CVD rates in North Americans relative to Japanese are due to blood cholesterol-independent risk factors. There is mounting evidence that DHA plus EPA from fish/fish oil can significantly reduce cardiovascular disease and mortality independently of lowering LDL-cholesterol levels. Many of the CVD risk parameters which are favorably affected by DHA/EPA are not routinely measured in the North American health care system. Interestingly, the intake of fish and DHA/EPA per day in Japan is many-fold higher than that for North Americans.

The published epidemiological studies from Daviglus et al. (see Figure 1 below) indicated that Americans who consumed at least 34 grams or more of fish per day on average had a 40-50% lower risk of myocardial infarctions, heart attacks, and much lower risk of coronary heart disease (CHD), CVD, and all-cause mortality. This intake (34 gm fish/day) is the equivalent of approximately 2 fatty fish servings per week which can be expected to deliver approximately 250-300 mg of DHA/EPA (combined) per day on average.

Figure 1: Relative risk of mortality according to fish consumption.

 

The 10-year MRFIT study reported by Dolecek correlated increased intakes of DHA/EPA (omega-3 fatty acids) as consumed by various sectors of the population with the relative risk of heart-related mortality. The findings are summarized in Figure 2 below. Increased consumptions of DHA/EPA up to 664 mg/day were associated with an approximate 40% reduction in CVD, CHD, and a significant reduction in all-cause mortality. An intake of 664 mg DHA/EPA per day would require approximately 5 fatty fish servings per week. Interestingly, current North American intakes of DHA/EPA (combined) represent approximately 130-150 mg/day or one-fourth of the 664 mg/day.

Figure 2: Relative Risks of Dietary n-3 Fish Fatty Acids Intake and Mortality

 

An overall review and meta-analysis of the various studies correlating fish consumption with CHD mortality has recently been published by He et al. (2004). Inclusion of the various cohort studies represents an evaluation of over 220,000 subjects followed over an average period of 11.8 years. As seen in Figure 3 , increased fish consumption per week was associated with a significant progressive reduction in CHD mortality. The highest apparent level of protection was observed at fish intakes of 5 or more servings per week which resulted in an apparent 35-45% reduction in the risk of CHD mortality. It is noteworthy that such a level of fish consumption represents approximately the equivalency of 650 mg/day of DHA/EPA (combined). This latter intake is essentially the target recommended by the 1999 NIH Workshop in Bethesda for optimal health and cardio care in normal healthy subjects.

Figure 3: CHD mortality and fish consumption

Daviglus, M.L., et al. Fish consumption and the 30-year risk of fatal myocardial infarction. N. Eng. J. Med. 336: 1046-53, 1997.

Dolecek, T.A. Epidemiological evidence of relationships between dietary polyunsaturated fatty acids and mortality in the Multiple Risk Factor Intervention Trial. PSEBM. 200:177-182, 1992.

Egus, G., and Yamane, K. Lifestyle, serum lipids and coronary artery disease: comparison of Japan with the United States . J. Atherscle. Thromb. 11(6):304-312, 2004.

He, K., et al. Accumulated evidence on fish consumption and coronary heart disease mortality: A meta-analysis of cohort studies. Circulation. 109: 2705-2711, 2004.

Holub, D. J., and Holub, B. J. Omega-3 fatty acids from fish oils and cardiovascular disease. Molecular and Cellular Biochemistry. 263:217-225, 2004.

Menotti, A., et al . Twenty-five-year coronary mortality trends in the seven countries study using the accelerated failure time model. Eur. J. Epidemiol. 18(2):113-122, 2003.

Simopoulos, A.P., et al. Essentiality of recommended dietary intakes for omega-6 and omega-3 fatty acids. Ann. Nutr. Metab. 43: 127-30, 1999.