Metabolic epidemiology of plasma cholesterol. Mechanisms of variation of plasma cholesterol within populations and between populations. International Collaborative Study Group.

Plasma cholesterol concentrations vary widely within and between populations, underlying a broad range of coronary heart disease mortality. Since the metabolic bases of this variation are poorly understood, low-density lipoprotein (LDL) metabolism was investigated, kinetically and in vitro, in five population samples from nutritionally disparate countries; 109 men with LDL cholesterol 1.0-6.7 mmol/l were studied. Slow production rate and rapid fractional catabolism, possibly due to high LDL receptor activity, underlay the lowest LDL cholesterol levels within each population; highest levels were largely maintained by rapid production rate. Differences in production rate explained more of the variation in LDL cholesterol than differences in fractional catabolic rate. Very low LDL levels in the African subjects were due to slow production rate; differences in fractional catabolic rate and production rate interacted in determining levels in the European populations. Direct relations were present between saturated fatty acid intake and production rate, and between monounsaturated fatty acid intake and fractional catabolic rate, and may contribute to differences in LDL metabolism between populations.