Paradoxical association of enhanced cholesterol efflux with increased incident cardiovascular risks.
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ABSTRACT:
SUBMITTER: Li XM
PROVIDER: S-EPMC3743250 | biostudies-literature | 2013 Jul
REPOSITORIES: biostudies-literature
Publications
Paradoxical association of enhanced cholesterol efflux with increased incident cardiovascular risks.
Li Xin-Min XM Tang Wai Hong Wilson WH Mosior Marian K MK Huang Ying Y Wu Yuping Y Matter William W Gao Vivian V Schmitt David D Didonato Joseph A JA Fisher Edward A EA Smith Jonathan D JD Hazen Stanley L SL
Arteriosclerosis, thrombosis, and vascular biology 20130321 7
<h4>Objective</h4>Diminished cholesterol efflux activity of apolipoprotein B (apoB)-depleted serum is associated with prevalent coronary artery disease, but its prognostic value for incident cardiovascular events is unclear. We investigated the relationship of cholesterol efflux activity with both prevalent coronary artery disease and incident development of major adverse cardiovascular events (death, myocardial infarction, or stroke).<h4>Approach and results</h4>Cholesterol efflux activity from ...[more]
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Project description:Background Elevated lipoprotein(a) is a well-established risk factor for atherosclerotic vascular disease but is not measured in routine clinical care. Screening of high lipoprotein(a) in individuals with moderate elevations of low-density lipoprotein cholesterol (LDL-C) may identify individuals at high risk of cardiovascular disease. Methods and Results We examined 2606 Framingham Offspring participants (median age, 54 years; 45% men) prospectively with a median follow-up of 15 years (n=392 incident cardiovascular events). Individuals with higher (≥100 nmol/L) versus lower lipoprotein(a) were divided into groups based on LDL-C <135 mg/dL versus ≥135 mg/dL. In Cox models, after adjustment for known risk factors, high lipoprotein(a) (≥100 nmol/L) and LDL-C ≥135 mg/dL were each significant predictors of cardiovascular disease (LDL-C ≥135 mg/dL: hazard ratio [HR], 1.34; 95% CI, 1.09-1.64; P=0.006; high lipoprotein (a): HR, 1.31; 95% CI, 1.03-1.66; P=0.026). Across the groups of high/low lipoprotein (a) and LDL-C ≥135 mg/dL or <135 mg/dL, the absolute cardiovascular disease risks at 15 years were 22.6% (high lipoprotein(a)/LDL-C ≥135 mg/dL, n=248), 17.3% (low lipoprotein(a)/LDL-C ≥135 mg/dL, n=758), 12.7% (high lipoprotein(a)/LDL-C <135 mg/dL, n=275) and 11.5% (low lipoprotein(a)/LDL-C <135 mg/dL, n=1328, reference group). Among individuals with LDL-C ≥135 mg/dL, those with high lipoprotein(a) had a 43% higher risk (HR, 1.43; 95% CI, 1.05-1.97; P=0.02). Presence of high lipoprotein(a) with moderate LDL-C levels (135-159 mg/dL) yielded absolute risks equivalent to those with LDL-C ≥160 mg/dL (23.5%, 95% CI, 17.4%-31.3%; and 20.7%, 95% CI, 16.8%-25.3%, respectively). Conclusions Concomitant elevation of LDL-C ≥135 mg/dL and lipoprotein(a) ≥100 nmol/L is associated with a high absolute risk of incident cardiovascular disease. lipoprotein(a) measurement in individuals with moderate elevations in LDL-C, who do not otherwise meet criteria for statins, may identify individuals at high cardiovascular risk.
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Project description:(1) Background and Aims: Efforts to reduce coronary artery disease (CAD) by raising high-density lipoprotein (HDL) cholesterol (HDL-C) have not been uniformly successful. A more important factor than HDL-C may be cellular cholesterol efflux mediated by HDL, which has been shown to be associated with CAD. In this report, we analyzed the influence of cardiovascular biomarkers and risk factors on cholesterol efflux in a prospective observational study of patients referred to coronary angiography. (2) Methods: HDL-mediated efflux capacity was determined for 2468 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study who were referred to coronary angiography at baseline between 1997 and 2000. Median follow-up time was 9.9 years. Primary and secondary endpoints were cardiovascular and all-cause mortality, respectively. (3) Results: Cholesterol efflux strongly correlated with HDL-related markers including HDL cholesterol, HDL phospholipids, and apolipoproteins AI and AII, as well as HDL particle concentration, which was not seen for low density lipoprotein (LDL) markers including LDL cholesterol and apoB. Cholesterol efflux was associated negatively with C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), and serum amyloid A. Cardiovascular mortality was higher in patients in the lowest cholesterol efflux quartile. This association was weakened, but not fully abolished, after adjustment for HDL cholesterol. (4) Conclusions: We demonstrate that cholesterol efflux was associated with HDL-composition as well as inflammatory burden in patients referred for coronary angiography, and that this inversely predicts cardiovascular mortality independently of HDL cholesterol.
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