PATHOPHYSIOLOGY AND NATURAL HISTORY HYPERLIPIDEMlA Seasonal cholesterol cycles: the Lipid Research Clinics Coronary Primary Prevention Trial placebo group

Seasonal variation of plasma cholesterol levels was studied in 1446 hypercholesterolemic 35to 59-year-old male participants in the Lipid Research Clinics Coronary Primary Prevention Trial placebo group. Each man's serial cholesterol data, obtained at bimonthly intervals for 2.0 to 6.5 years, were analyzed as a separate periodic time series, and distributions of cycle zeniths and amplitudes were calculated. A highly significant (X2 = 706, 2 degrees of freedom) seasonal effect, 7.4 mg/dl higher on December 30 than on June 30, was found. This effect was similar among the 12 LRC centers, including such disparate climates as those of Minneapolis and San Diego, and tended to be larger in the southern centers. Its magnitude was independent of baseline levels of plasma cholesterol and other baseline characteristics. Observed seasonal differences in weight and diet explained less than one-third of the seasonal variation in plasma cholesterol levels. Plasma lowand high-density lipoprotein cholesterol levels, analyzed similarly, also showed significant synchronous seasonal cycles. Plasma triglyceride levels showed a weaker irregular seasonal pattern, highest in midsummer and late autumn and lowest in spring. The etiologies and mechanisms for these seasonal patterns remain largely unknown. Circulation 76, No. 6, 1224-1231, 1987. CYCLIC SEASONAL VARIATION in circulating cholesterol levels has been studied in a variety of settings'-4during the past 60 years and has intrigued biologists interested in the regulation of pathways of cholesterol metabolism as well as clinicians interested in recognizing and treating hypercholesterolemia. However, since none of these studies involved frequent (i.e., several per year) serial cholesterol determinations in an adequate stable cohort over at least two annual cycles, much ambiguity remains. Although these studFrom the Lipid Metabolism-Atherogenesis Branch, DHVD, NHLBI, National Institutes of Health, Bethesda, MD; E. R. Squibb and Sons, Princeton, NJ; Department of Pathology, George Washington University, Washington, DC; Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina, Chapel Hill, NC; Division of Epidemiology, University of Minnesota, School of Public Health, Minneapolis, MN. This work was supported by National Heart, Lung, and Blood Institute contracts numbered: NOI-HV12159, NOI-HV12156, NOIHV32961, NOI-HV12160, NOI-HV22914, NOI-HV32931, N01HV22913, NOI-HV12158, N01-HV12161, NOI-HV22915, NOI-HV12903, NOI-HV12243, NOI-HV22932, NOI-HV22917, NOIHV22916, NOI-HV12157, and YOI-HV30010. Address for correspondence: Basil M. Rifkind, M.D., F.R.C.P., Chief, Lipid Metabolism-Atherogenesis Branch, Division of Heart and Vascular Diseases, NIH, Bethesda, MD 20892. Received June 29, 1987; revision accepted Aug. 27, 1987. 1224 ies convey the overall impression that cholesterol levels are higher in winter than in summer, one critical reviewer found the evidence for this "common and strongly held belief' less than compelling.' The present report describes the cyclic seasonal variation of plasma lipid levels observed in the placebo cohort of the Lipid Research Clinics (LRC) Coronary Primary Prevention Trial (CPPT).f-7 This cohort of 1899 hypercholesterolemic 35to 59-year-old men, initially free of symptomatic coronary heart disease, was maintained on a standard diet and examined bimonthly for 7 to 10 years. Because of its longitudinal design, the large number of participants, the number and frequency of lipid measurements obtained for each participant, and the uniformity of methods and laboratory performance standards among the 12 LRC centers, the LRC-CPPT offered a unique opportunity to study seasonal cycles in a variety of geographic settings. In addition, the bimonthly measurement of lipoprotein cholesterol levels and body weight and the semiannual assessment of diet provided an opportunity to address some components and correlates of these cycles. CIRCULATION by gest on A ril 9, 2017 http://ciajournals.org/ D ow nladed from PATHOPHYSIOLOGY AND NATURAL HISTORY-HYPERLIPIDEMIA