Elevated lipoprotein(a) levels and small apo(a) isoforms are compatible with longevity: evidence from a large population of French centenarians.

Epidemiological studies have shown lipoprotein(a) (Lp(a)) to be an independent risk factor for cardiovascular disease. Lp(a) is a cholesterol-rich, low-density lipoprotein (LDL)-like particle to which a large glycoprotein, apolipoprotein(a) (apo(a)) is attached. Plasma Lp(a) levels are highly genetically determined and influenced to a minor degree by environmental factors. In an effort to determine whether Lp(a) might be associated with longevity, we have evaluated Lp(a) levels and apo(a) isoform sizes in a population of French centenarians (n = 109) compared to a control group (n = 227). The mean age of centenarians was 101.5 +/- 2.4 years while the control group was 39.4 +/- 7.2 years. Plasma levels of total cholesterol and triglyceride were within the normal range in both centenarian and control subjects. Lp(a) levels were higher in centenarians (both male and female) than in the normolipidemic control group (mean Lp(a) level = 0.33 +/- 0.42 and 0.22 +/- 0.27 mg/ml, respectively, P < 0.005). The distribution of apo(a) isoforms was significantly shifted towards small isoform size in the centenarian population as compared to the controls (54.4 and 41.4% of isoforms < or = 27 kringles (kr), respectively, P = 0.04). Nonetheless, the apo(a) size distribution in centenarians did not entirely explain the high Lp(a) levels observed in this population. Factors other than apo(a) size, and which may be either genetic or environmental in nature, appear to contribute to the elevated plasma Lp(a) levels of our centenarian population. We conclude therefore that high plasma Lp(a) levels are compatible with longevity.