Complementary prediction of cardiovascular events by estimated apo- and lipoprotein concentrations in the working age population. The Health 2000 Study

Department of Clinical Chemistry, Fimlab Laboratories, Tampere University Hospital and University of Tampere School of Medicine , Tampere , Finland.
Annals of Medicine (Impact Factor: 3.89). 04/2012; 45(2). DOI: 10.3109/07853890.2012.679962
Source: PubMed


Background. Apolipoprotein A-I (apoA-I) and B (apoB) and multiple lipoprotein cardiovascular risk factors can be computationally estimated with our extended Friedewald approach (EFW) from classical inputs. Their impact on cardiovascular events and mortality in the working age population is not known. Methods. The working age (≤ 65 years, n = 5956) prospective population-based cohort (follow-up of 7.8 ± 0.9 years; 46,572 patient years, 409 non-fatal incident cardiovascular events, and 55 cardiovascular and 266 all-cause deaths) had their total serum cholesterol (TC), triglycerides (TG), and HDL-C measured. Continuous net reclassification improvement (NRI) was calculated. Results. In Cox models adjusted with cardiovascular risk factors, EFW-HDL(2)-C (HR 0.78, 95% CI 0.67-0.91; NRI 16.5%), apoA-I (HR 0.78, 95% CI 0.69-0.89; NRI 15.2%), apoB/apoA-I (HR 1.23, 95% CI 1.08-1.40; NRI 20.6%), and VLDL-TG (HR 1.15, 95% CI 1.05-1.25; NRI 20.1%) were associated with incident non-fatal cardiovascular events and improved risk prediction compared with TC, LDL-C, or non-HDL-C. Cardiovascular deaths could be best predicted with EFW apoB (HR 1.81, 95% CI 1.18-2.77; NRI 77.3%). Conclusions. EFW approach-derived HDL(2)-C, apoA-I, apoB/apoA-I, and VLDL-TG improve prediction of non-fatal cardiovascular events, and apoB of cardiovascular mortality, and can be utilized for risk estimation in a working age population without extra cost.

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    • "Moreover, the relevance of HDL subfractions for cardiovascular risk prediction has received considerable attention[6,9,12,17,28]. As yet, the importance of larger-sized compared to smaller-sized HDL particles for coronary risk has not been unequivocally established, neither in the setting of population-based cohort studies[9,12,17,28], nor in specific high risk populations[3,4,37]. Of further interest, low HDL cholesterol as determined during an acute coronary syndrome may predict recurrent cardiovascular events[38]. "
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    ABSTRACT: Objective: Metformin affects low density lipoprotein (LDL) and high density (HDL) subfractions in the context of impaired glucose tolerance, but its effects in the setting of acute myocardial infarction (MI) are unknown. We determined whether metformin administration affects lipoprotein subfractions 4 months after ST-segment elevation MI (STEMI). Second, we assessed associations of lipoprotein subfractions with left ventricular ejection fraction (LVEF) and infarct size 4 months after STEMI. Methods: 371 participants without known diabetes participating in the GIPS-III trial, a placebo controlled, double-blind randomized trial studying the effect of metformin (500 mg bid) during 4 months after primary percutaneous coronary intervention for STEMI were included of whom 317 completed follow-up ( Identifier: NCT01217307). Lipoprotein subfractions were measured using nuclear magnetic resonance spectroscopy at presentation, 24 hours and 4 months after STEMI. (Apo)lipoprotein measures were obtained during acute STEMI and 4 months post-STEMI. LVEF and infarct size were measured by cardiac magnetic resonance imaging. Results: Metformin treatment slightly decreased LDL cholesterol levels (adjusted P = 0.01), whereas apoB remained unchanged. Large LDL particles and LDL size were also decreased after metformin treatment (adjusted P<0.001). After adjustment for covariates, increased small HDL particles at 24 hours after STEMI predicted higher LVEF (P = 0.005). In addition, increased medium-sized VLDL particles at the same time point predicted a smaller infarct size (P<0.001). Conclusion: LDL cholesterol and large LDL particles were decreased during 4 months treatment with metformin started early after MI. Higher small HDL and medium VLDL particle concentrations are associated with favorable LVEF and infarct size.
    Full-text · Article · Jan 2016 · PLoS ONE