The intake of polyunsaturated fatty acids and cardiovascular diseases

Background Despite a large amount of research in the past decades, the role of polyunsaturated fatty acids (PUFA) in the prevention of coronary heart disease (CHD) and stroke is still debated. Inconsistent findings in epidemiological studies may be due to methodological limitations of dietary assessment, which could be overcome by using PUFA levels in blood as a biomarker of intake. This thesis investigates dietary intake and plasma levels of various n-6 and n-3 PUFA in relation to CHD and stroke within a population-based sample in the Netherlands. Methods The associations of dietary intake of PUFA (assessed by food-frequency questionnaire) with incident CHD and stroke were examined in cohort studies. PUFA levels in plasma cholesteryl esters were measured in nested case-control studies. N-6 PUFA included linoleic acid and arachidonic acid and the n-3 PUFA included the marine-derived eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the plant-derived alpha-linolenic acid (ALA). We used the “Monitoring Project on Cardiovascular Disease Risk Factors“ and the “Monitoring Project on Risk Factors for Chronic Diseases” (MORGEN study), two large similar population-based cohorts with baseline measurements in 1987-1997 and follow-up for CHD and stroke incidence. Additionally, we performed a meta-analysis of prospective epidemiological studies on PUFA in cholesteryl esters and CHD risk. Results A 4-5 en% difference in linoleic acid intake was not associated with incident CHD, whereas plasma linoleic acidwas inversely, but statistically non-significantly, associated with fatal CHD. In the meta-analysis, a 5% higher plasma linoleic acid level was related to a significant 9% lower CHD risk. Both ALA intake and status were not associated with CHD. The top quartiles of EPA-DHA (~250 mg/d) and fish intake (~1 fish meal/week) were related to a ~50% lower risk of fatal CHD compared to the bottom quartiles. However, this was not confirmed in plasma EPA-DHA. An ALA intake ≥1.1 g/d was associated with a 35-50% lower stroke incidence, compared with lower intakes. In women, but not in men, a significantly inverse relation was observed for EPA-DHA and fish intake with incident stroke, with a ~50% lower risk in the top quartile compared with the bottom quartile. Plasma PUFA levels were, however, not related to incident stroke. Conclusion The hypothesis of a beneficial effect of linoleic acid on CHD was confirmed in our biomarker study, but not in the study that used dietary intake data. For EPA-DHA, on the other hand, dietary intake was inversely related to fatal CHD and incident stroke, whereas cholesteryl ester EPA-DHA were not associated. The same applied to ALA intake in relation to incident stroke. Inconsistencies between PUFA intake and status with cardiovascular diseases could be attributed to the limited range of variation in PUFA intake in combination with measurement error. </p