Motivation: Lipoprotein (a) inspires strong emotions among doctors. Some like it as a risk factor while others see it as a waste of money. But, when controlled for conventional lipid markers, is it indicative for additional risk for cardiovascular disease? For background, lipoprotein (a) is a low density LDL-like particle synthesized by the liver which is found in the intima of arteries and presumably promotes atherosclerosis.
Paper: The Emerging Risk Factors Collaboration. "Lipoprotein (a) Concentration and the Risk of Coronary Heart Disease, Stroke, and Nonvascular Mortality." JAMA (2009); 302: 412-423.
Methods: Meta-analysis of long-term prospective studies that recorded Lipoprotein (a) (Lp(a)) and vascular morbidity.
Results:
Studies: 36 prospective studies met inclusion criteria. In the analysis, 126 634 participants were included for 1.3 million person-year of follow-up with 22 076 vascular disease outcomes or death. Mean age at entry was 57 years with 48% women. Ethnicity was 47% European and 50% North American.
Lipoprotein (a): At baseline, the overall population Lp (a) was 12.6 mg/dL. Blacks had 119% (95% CI: 84 to 161) higher Lp(a) concentration compared to whites at baseline. Women had 12% (CI: 8 to 16) higher Lp (a) than men.
Coronary Heart Disease (CHD): When adjusted for age, sex, systolic blood pressure, smoking, diabetes, and total cholesterol, the relative risk of coronary heart disease for the top third of Lp (a) compared to the bottom third was 1.27 (95% CI: 1.17-1.38). In the top third of subjects with Lp (a), the rate of CHD was 5.6 (95% CI: 5.4-5.9) per 1000 person years compared to rate of 4.4 (95% CI: 4.2-4.6) per 1000 person years in the bottom third.
Ischemic Stroke: When adjusted for usual risk factors, the relative risk (RR) for ischemic stroke was 1.10 (95% CI: 1.02-1.18) per 3.5 fold higher than usual Lp (a) levels. The relative risk did not reach significance for unclassified stroke and hemorrhagic stroke.
Non-vascular mortality: Lp (a) levels were not associated with increase in non-vascular mortality.
Discussion: Lipoprotein (a) is very modestly associated with independent risk of coronary heart disease and ischemic stroke. As stated in the paper, compared to the power of Lp (a), elevated non-HDL cholesterol level is four times more strongly associated with coronary heart disease. There is no drug that independently targets Lp (a) levels. Consequently, I do not think that at present, it is worth measuring this modestly predictive marker without clear treatment. The paper, though, illuminated the variability of Lp (a) across ethnicities (blacks have baseline of 100% greater than whites) and genders. When interpreting raw values of Lp (a), we have to be careful about using correct gender and ethnicity matched norms, which may not exist in all cases.
Paper: The Emerging Risk Factors Collaboration. "Lipoprotein (a) Concentration and the Risk of Coronary Heart Disease, Stroke, and Nonvascular Mortality." JAMA (2009); 302: 412-423.
Methods: Meta-analysis of long-term prospective studies that recorded Lipoprotein (a) (Lp(a)) and vascular morbidity.
Results:
Studies: 36 prospective studies met inclusion criteria. In the analysis, 126 634 participants were included for 1.3 million person-year of follow-up with 22 076 vascular disease outcomes or death. Mean age at entry was 57 years with 48% women. Ethnicity was 47% European and 50% North American.
Lipoprotein (a): At baseline, the overall population Lp (a) was 12.6 mg/dL. Blacks had 119% (95% CI: 84 to 161) higher Lp(a) concentration compared to whites at baseline. Women had 12% (CI: 8 to 16) higher Lp (a) than men.
Coronary Heart Disease (CHD): When adjusted for age, sex, systolic blood pressure, smoking, diabetes, and total cholesterol, the relative risk of coronary heart disease for the top third of Lp (a) compared to the bottom third was 1.27 (95% CI: 1.17-1.38). In the top third of subjects with Lp (a), the rate of CHD was 5.6 (95% CI: 5.4-5.9) per 1000 person years compared to rate of 4.4 (95% CI: 4.2-4.6) per 1000 person years in the bottom third.
Ischemic Stroke: When adjusted for usual risk factors, the relative risk (RR) for ischemic stroke was 1.10 (95% CI: 1.02-1.18) per 3.5 fold higher than usual Lp (a) levels. The relative risk did not reach significance for unclassified stroke and hemorrhagic stroke.
Non-vascular mortality: Lp (a) levels were not associated with increase in non-vascular mortality.
Discussion: Lipoprotein (a) is very modestly associated with independent risk of coronary heart disease and ischemic stroke. As stated in the paper, compared to the power of Lp (a), elevated non-HDL cholesterol level is four times more strongly associated with coronary heart disease. There is no drug that independently targets Lp (a) levels. Consequently, I do not think that at present, it is worth measuring this modestly predictive marker without clear treatment. The paper, though, illuminated the variability of Lp (a) across ethnicities (blacks have baseline of 100% greater than whites) and genders. When interpreting raw values of Lp (a), we have to be careful about using correct gender and ethnicity matched norms, which may not exist in all cases.
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