Aggregation of lipoprotein(a) to apolipoprotein A-I underlying HDL dysfunction as a major coronary risk factor

Onat, Altan; Can, Giinay; Murat, Sani; Çiçek, Gökhan; Örnek, Ender; Yüksel, Hüşniye
September 2013
Anatolian Journal of Cardiology / Anadolu Kardiyoloji Dergisi;Sep2013, Vol. 13 Issue 6, p543
Academic Journal
Objective: Dysfunction of high-density lipoprotein (HDL) may contribute to coronary heart disease (CHD) risk. We determined whether aggregation to lipoprotein (Lp)(a) of apolipoprotein (apo) A-I underlies HDL dysfunction conferring incident CHD risk. Methods: A representative sample of 1509 middle-aged Turkish adults was studied at 4.9-years' follow-up yielding 198 incident CHD cases. Statistical analysis was performed using multiple linear regression and Cox proportional regression analyses. Results: In women, not age or apoA-l, rather complement C3, apoE levels and statin use were linearly related to log-Lp(a). Individuals in the low Lp(a) tertile (<6.4 mg/dL) displayed high mean triglyceride and apoE values, and geometric mean Lp(a) values increased moderately in subjects having low and mid tertiles of apoE or triglycerides, only to be lower in the high tertiles (p<0.002). These two findings indicated the unexpected fall in Lp(a) under circumstances of high apo E (>4.5 mg/dL) and/or triglycerides (>2.0 mmol/L). Levels actually represent aggregation of Lp(a) to apoA-l in an immune complex, rendering apoA-l atherogenic. Lp(a) did not, but apoA-l did significantly predict incident CHD (HR 1.21 [95%CI 1.07; 1.37]) in Cox regression analyses after adjustment for conventional risk factors and statin use. This adverse action of apoA-l was independent of prevalent metabolic syndrome (MetS), existed in individuals in whom ATPIII-defined MetS was not identified, and was similar in magnitude to that of conventional risk factors. Conclusion: Beyond being atherogenic, Lp(a) may aggregate in a pro-inflammatory milieu to apoA-l, rendering apoA-l atherogenic. This process is independent of ATPIII-defined MetS and exhibits risk magnitude similar to that of conventional risk factors.


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