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Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study
Gérald Luc1, Jean-Marie Bard, Dominique Arveiler
1Department of Atherosclerosis, INSERM UR545, Pasteur Institute of Lille, 1, rue du Professeur Calmette, France and University Lille II, France. gerald.luc@pasteur-lille.fr
Insights
Elevated lipoprotein (a) (Lp(a)) is a significant risk factor for coronary heart disease (CHD), particularly in men with high LDL-cholesterol. This finding confirms Lp(a) as a valuable predictor of myocardial infarction and angina pectoris.
Area of Science:
- Cardiology
- Epidemiology
- Biochemistry
Background:
- The role of elevated lipoprotein (a) (Lp(a)) in coronary heart disease (CHD) development is debated.
- Lp(a) is an independent risk factor for cardiovascular disease.
- Understanding Lp(a)'s association with CHD is crucial for risk stratification.
Purpose of the Study:
- To investigate lipoprotein (a) (Lp(a)) as a coronary heart disease (CHD) risk factor in a large prospective cohort.
- To evaluate the interaction between Lp(a) and traditional cardiovascular risk factors, specifically LDL- and HDL-cholesterol.
- To confirm the utility of Lp(a) as a predictor of CHD events.
Main Methods:
- Prospective cohort study (PRIME Study) involving 9133 French and Northern Irish men aged 50-59.
- Follow-up of 5 years with assessment of CHD events (myocardial infarction, coronary death, angina pectoris).
- Measurement of Lp(a) by immunoassay on fresh plasma; logistic regression analysis controlling for cardiovascular risk factors.
Main Results:
- Elevated Lp(a) was a significant CHD risk factor (P<0.0006) in the overall cohort.
- Men in the highest Lp(a) quartile had a 1.56-fold increased risk of CHD events compared to the lowest quartile.
- A significant interaction was found between Lp(a) and LDL-cholesterol, with increased risk in men with high levels of both.
Conclusions:
- Lipoprotein (a) (Lp(a)) is confirmed as a significant predictor of coronary heart disease (CHD), including myocardial infarction and angina pectoris.
- The CHD risk associated with Lp(a) is amplified in individuals with high LDL-cholesterol levels.
- Lp(a) measurement is a valuable tool for predicting CHD events, especially when considered alongside LDL-cholesterol.
Abstract:
The association of an elevated level of lipoprotein (a) (Lp(a)) with the development of coronary heart disease (CHD) remains controversial. Lp(a) was investigated as a CHD risk factor in the PRIME Study, a prospective cohort study which included 9133 French and Northern Irish men aged 50-59 at entry, without a history of CHD and not on hypolipidaemic drugs. During a follow-up of 5 years, 288 subjects experienced at least one CHD event (myocardial infarction (MI), coronary death, angina pectoris). Lp(a) was measured by immunoassay in all subjects on fresh plasma obtained at entry. Traditional cardiovascular risk factors such as low-density lipoproteins (LDL)-cholesterol, HDL-cholesterol, triglycerides, the presence of diabetes, hypertension or smoking were determined. Logistic regression analysis was used to evaluate Lp(a) level as a CHD risk factor after controlling for the other risk factors. In addition, its possible interaction with LDL- and HDL-cholesterol levels was investigated. Lp(a) appeared a significant risk factor (P<0.0006) in the whole cohort without between-population interaction, even if the association was not statistically significant in the Belfast sample. The relative risk (RR) of CHD events in subjects with Lp(a) levels in the highest quartile was 1.5 times that of subjects in the lowest quartile (RR: 1.56; 95% confidence intervals (CIs): 1.10-2.21). A high Lp(a) level was a risk for MI, coronary death and angina pectoris. A significant interaction term between Lp(a) and LDL-cholesterol levels, however, was found. The relative CHD risk associated with a Lp(a) level > or =33 mg/dl in comparison with Lp(a) <33 mg/dl increasing gradually from 0.82 (95% CI: 0.28-2.44) in men with LDL-cholesterol in the lowest quartile (<121 mg/dl) to 1.58 (95% CI: 1.06-2.40) in the highest quartile (>163 mg/dl). In conclusion, Lp(a) increased the risk for MI and angina pectoris, especially in men with a high LDL-cholesterol level. This study which analyzed Lp(a) level using a measurement independent of apolipoprotein (a) size on fresh plasma, has confirmed utility of Lp(a) as a predictor of CHD.