A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women. The Framingham Heart Study.

BACKGROUND Sinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein (a). Although prospective data suggest that increased plasma lipoprotein (a) is an independent risk factor for coronary heart disease in men, no prospective studies are available in women. METHODS AND RESULTS From 1968 through 1975, sinking prebeta lipoprotein was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease. A sinking prebeta lipoprotein band was detectable in 434 of the women (14%) studied. The median follow-up interval was approximately 12 years. Incident cardiovascular disease was associated with band presence using a proportional hazards model that included age, smoking, body mass index, systolic blood pressure, glucose intolerance, low- and high-density lipoprotein cholesterol, and ECG left ventricular hypertrophy. Multivariable adjusted relative risk estimates (with 95% confidence intervals) for outcomes in the band present versus absent groups were as follows: myocardial infarction (82 events), 2.37 (1.48 to 3.81); intermittent claudication (62 events), 1.94 (1.07 to 3.50); cerebrovascular disease (83 events), 1.88 (1.12 to 3.15); total coronary heart disease (174 events), 1.61 (1.13 to 2.29); and total cardiovascular disease (305 events), 1.44 (1.09 to 1.91). A subset analysis indicated that band presence was 50.9% sensitive and 95.4% specific for detecting plasma lipoprotein (a) levels of > 30 mg/dL, the threshold value linked to increased cardiovascular disease risk in men. CONCLUSIONS Sinking prebeta lipoprotein was a valid surrogate for elevated lipoprotein (a) levels in Framingham Heart Study women. Band presence and, equivalently, elevated plasma lipoprotein (a), was a strong, independent predictor of myocardial infarction, intermittent claudication, and cerebrovascular disease. Confirmation of these findings in other longitudinal studies of women is needed.