For years, treating dyslipidemia mainly focused on reducing LDL cholesterol (LDL-C) with statins, which had shown benefits in reducing atherosclerotic cardiovascular disease (ASCVD). Lipoprotein(a) [Lp(a)] is a form of apoB-containing lipoprotein bound to a hydrophilic, highly glycosylated protein called apolipoprotein(a) [apo(a)]. Circulating levels of Lp(a) are genetically determined, and are hardly affected by eating habits or lifestyle.
Elevated levels of Lp(a) have been associated with higher risk of developing ASCVD, according to randomized studies and Mendelian analysis, which include new events incidence such as acute myocardial infarction (AMI), stroke and peripheral artery disease. The correlation between Lp(a) and ASCVD risk is linear, both at baseline conditions and during statin treatment. However, it has not been completely established how to predict long term risk in cohorts with elevated baseline risk at primary prevention, including diabetic patients.
The aim of this study was to examine the comparative relationship of Lp(a) with ASCVD events in an American cohort at mean 20 year followup, including persons without known cardiovascular disease, at low and high risk of ASCVD, was well as a specific analysis of those with diabetes diabetes mellitus (DM).
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The study included data from five prospective studies on cardiovascular disease, the MESA, CARDIA, JHS, FHS-OS and ARIC, from 1983 to 2002, at 36-year followup (mean 21 years).
Lp(a) was categorized in percentils (<50th, 50th to <75th, 75th to <90th and >90th), and patients were classified according to ASCVD risk into low-intermediate (<20% ACVD risk at 10 years) and high risk (>20% at 10 años). For patients from 20 to <40 years, high risk was defined as two or more risk factors, such as active smoking, DM, high BP, LDL-C ≥100mg/dl, HDL-C ≤40 mg/dl (men) or ≤50 mg/dl (women) and BMI ≥30 kg/m². ASCVD primary end point included non-fatal and fatal AMI, stroke, revascularization, and death for coronary artery disease.
It included 27,756 patients without known cardiovascular disease, rainging between 20 and 79 years of age ( mean 51.2 ± 12.4 years), 55% women, 2.5% asian, 4.7% hispanic and 35.6% dark skinned at 21.1 ± 9.9-year mean followup. 82.4% presented low-intermediate risk and 17.6% high risk, including 7.6% with DM. Mean Lp(a) valules for percentils (<50th, 50th to <75th, 75th to <90th and >90th) were 3.6, 13.5, 25.9 and 52.6 mg/dL respectively. Patients with higher levels of Lp(a) tended to be women, black and had higher education.
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Compared against people in the <50th percentil, those with higher percentils of Lp(a) had adusted HR 1.06 (CI 95%: 0.99-1.14), 1.18 (CI 95%: 1.09-1.28) and 1.46 (CI 95%: 1.33-1.59) respectively. HR resulted similar when stratifying between low-intermediate and high risk (interaction P = 0.88); however, it resulted higher in those with DM (interaction P=0.0056). When looking at DM population, in those with >90 Lp(a) percentil, CV events risk was nearly twice as high (HR: 1.92; CI 95%: 1.50-2.45).
Conclusions
This analysis shows elevated levels of Lp(a) are independently associated to higher risk of ASCVD during +20 year followup, and that this is a more significant and hierarchical relationship for patients with diabetes mellitus.
Dr. Omar Tupayachi.
Member of the Editorial Board of SOLACI.org.
Original Title: Lipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic Pooled Prospective Cohort.
Reference: Wong ND, Fan W, Hu X, Ballantyne C, Hoodgeveen RC, Tsai MY, Browne A, Budoff MJ. Lipoprotein(a) and Long-Term Cardiovascular Risk in a Multi-Ethnic Pooled Prospective Cohort. J Am Coll Cardiol. 2024 Apr 23;83(16):1511-1525. doi: 10.1016/j.jacc.2024.02.031. PMID: 38631771.
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