Congestive heart failure is associated with lipoprotein components in statin-treated patients with coronary heart disease Insights from the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL)

• Published in: Atherosclerosis 2009-08, Vol.205 (2), p.522-527
• Main Authors: HOLME, Ingar, STRANDBERG, Timo E, FAERGEMAN, Ole, KASTELEIN, John J. P, OLSSON, Anders G, TIKKANEN, Matti J, LARSEN, Mogens Lytken, LINDAHL, Christina, PEDERSEN, Terje R
• Format: Article
• Language: English
• Subjects: Aged; Apolipoproteins; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Congestive heart failure; Coronary Disease - complications; Coronary Disease - drug therapy; Female; General and cellular metabolism. Vitamins; Heart Failure - complications; Heart Failure - diagnosis; Heart Failure - prevention & control; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Lipids - blood; Lipoproteins; Lipoproteins - blood; Male; Medical sciences; MEDICIN; MEDICINE; Middle Aged; Models, Statistical; Pharmacology. Drug treatments; Predictive Value of Tests; Proportional Hazards Models; Risk; Risk Factors; Risk prediction; Simvastatin - pharmacology; Statin
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2009.01.023

Very few, if any, studies have assessed the ability of apolipoproteins to predict new-onset of congestive heart failure (HF) in statin-treated patients with coronary heart disease (CHD). To employ the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL) study database to assess the association of on-treatment lipoprotein components with prediction of HF events and to compare their predictive value with that of established risk factors such as hypertension and diabetes. We used Cox regression models to study the relationships between on-treatment levels of apolipoproteins A1 and B to subsequent HF. Chi square information value from the log likelihood was used to compare the predictive value of lipoprotein components with established risk factors of HF. In the IDEAL study, on-treatment apolipoproteins proved to be associated with the occurrence of new-onset HF. Variables related to low-density lipoprotein cholesterol (LDL-C) carried less predictive information than those related to high-density lipoprotein cholesterol (HDL-C), and apoA-1 was the single variable most strongly associated with HF. LDL-C was less predictive than both non-HDL-C (total cholesterol minus HDL-C) and apoB. The ratio of apoB to apoA-1 was most strongly related to HF after adjustment for potential confounders, among which diabetes had a stronger correlation with HF than did hypertension. ApoB/apoA-1 carried approximately 2.2 times more of the statistical information value than that of diabetes. Calculation of the net reclassification improvement index revealed that about 3.7% of the patients had to be reclassified into more correct categories of risk once apoB/apoA-1 was added to the adjustment factors. The reduction in risk by intensive lipid-lowering treatment as compared to usual-dose simvastatin was well predicted by the difference in apoB/apoA-1 on-treatment levels. The on-treatment ratio of apoB/apoA-1 was the strongest predictor of HF in CHD patients of both IDEAL treatment arms combined, mostly driven by the strong association with apoA-1, whereas LDL-C and non-HDL-C were less able to predict HF outcome. The predictive information value contained within apoB/apoA-1 was about 2.2 times more than that of diabetes. Between-treatment group differences in HF were to a significant extent explained by on-treatment differences in apoB/apoA-1, mostly through the changes in apoB. We argue therefore, on-treatment lipoprotein components contribute to the overa