Do associations with C-Reactive protein and extent of coronary artery disease account for the increased cardiovascular risk of renal insufficiency?

AbstractObjectivesWe sought to determine whether the association of higher C-reactive protein levels (CRP) and more extensive coronary artery disease (CAD) explains the high cardiovascular risk of renal insufficiency (RI).BackgroundRenal insufficiency and renal failure (RF) have been associated with increased cardiovascular risk in several studies, and it has been suggested that this association may be due to higher CRP levels and greater extent of CAD. To what extent CRP or severity of CAD explains this risk is uncertain.MethodsA total of 1,484 patients without myocardial infarction (MI) undergoing angiography were entered and followed for 3.0 ± 1.6 years; RI and RF were defined as estimated glomerular filtration rates (GFR) of 30 to 60 and <30 ml/min; CRP was measured by immunoassay and ≥ 1.0 mg/dl defined as elevated. A CAD score was determined by extent and severity of angiographic disease. Multivariate Cox regressions were performed using seven standard risk factors, homocysteine, GFR, CRP, and CAD score.ResultsMean age was 64 years, and 67% were men; CAD was absent in 24%, mild in 11%, and severe (≥70% stenosis) in 60%; CRP and CAD scores increased with declining renal function (median CRP: 1.2, 1.4, 2.2 mg/dl, p < 0.001 and CAD score: 8.1, 8.7, 9.3, p = 0.008 for no-RI, RI, and RF). During follow-up, 208 patients (15%) died or had nonfatal MI. Unadjusted hazard ratio (HR) for death/MI was 2.3 for RI and 5.1 for RF (p < 0.0001). Adjustment for CRP (HR, 2.2, 4.5), CAD score (HR, 2.1, 5.1), and all other risk factors (HR, 1.7, 4.5) had minimal or modest impact on RI and RF risk; HR increased to 5.4 (p < 0.001) for presence of both elevated CRP and RI/RF.ConclusionsRenal insufficiency, CRP, and angiographic CAD, although correlated, are largely independent predictors of cardiovascular risk, suggesting the importance of both inflammation and as yet undefined RI-related risk factors

Statin therapy is associated with reduced mortality across all age groups of individuals with significant coronary disease, including very elderly patients

AbstractObjectivesThis study evaluated the effect of statin therapy on mortality in individuals with significant coronary artery disease (CAD) stratified by age.BackgroundHydroxymethylglutaryl coenzyme A reductase inhibitors (statins) significantly reduce morbidity and mortality in individuals with CAD. Unfortunately, the large statin trials excluded individuals over 80 years old, and it is therefore unknown whether very elderly individuals benefit from statins as do younger individuals.MethodsA cohort of 7,220 individuals with angiographically defined significant CAD (≥70%) was included. Statin prescription was determined at hospital discharge. Patients were followed up for 3.3 ± 1.8 years (maximum 6.8). Patients were grouped by age (<65, 65 to 79, and ≥80 years) to determine whether statin therapy reduced mortality in an age-dependent manner.ResultsAverage age was 65 ± 12 years; 74% were male; and 31% had a postmyocardial infarction status. Overall mortality was 16%. Elderly patients were significantly less likely to receive statins than younger patients (≥80 years: 19.8%; 65 to 79 years: 21.1%; <65 years: 28.0%; p < 0.001). Mortality was decreased among statin recipients in all age groups: ≥80 years: 29.5% among patients not taking a statin versus 8.5% of those taking a statin (adjusted hazard ratio [HR] 0.50, p = 0.036); 65 to 79 years: 18.7% vs. 6.0% (HR 0.56, p < 0.001); and <65 years: 8.9% vs. 3.1% (HR 0.70, p = 0.097).ConclusionsStatin therapy is associated with reduced mortality in all age groups of individuals with significant CAD, including very elderly individuals. Although older patients were less likely to receive statin therapy, they received a greater absolute risk reduction than younger individuals. More aggressive statin use after CAD diagnosis may be indicated, even in older patients

Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events

IntroductionLong-chain omega-3 polyunsaturated fatty acids (OM3 PUFA) are commonly used for cardiovascular disease prevention. High-dose eicosapentaenoic acid (EPA) is reported to reduce major adverse cardiovascular events (MACE); however, a combined EPA and docosahexaenoic acid (DHA) supplementation has not been proven to do so. This study aimed to evaluate the potential interaction between EPA and DHA levels on long-term MACE.MethodsWe studied a cohort of 987 randomly selected subjects enrolled in the INSPIRE biobank registry who underwent coronary angiography. We used rapid throughput liquid chromatography-mass spectrometry to quantify the EPA and DHA plasma levels and examined their impact unadjusted, adjusted for one another, and fully adjusted for comorbidities, EPA + DHA, and the EPA/DHA ratio on long-term (10-year) MACE (all-cause death, myocardial infarction, stroke, heart failure hospitalization).ResultsThe average subject age was 61.5 ± 12.2 years, 57% were male, 41% were obese, 42% had severe coronary artery disease (CAD), and 311 (31.5%) had a MACE. The 10-year MACE unadjusted hazard ratio (HR) for the highest (fourth) vs. lowest (first) quartile (Q) of EPA was HR = 0.48 (95% CI: 0.35, 0.67). The adjustment for DHA changed the HR to 0.30 (CI: 0.19, 0.49), and an additional adjustment for baseline differences changed the HR to 0.36 (CI: 0.22, 0.58). Conversely, unadjusted DHA did not significantly predict MACE, but adjustment for EPA resulted in a 1.81-fold higher risk of MACE (CI: 1.14, 2.90) for Q4 vs. Q1. However, after the adjustment for baseline differences, the risk of MACE was not significant for DHA (HR = 1.37; CI: 0.85, 2.20). An EPA/DHA ratio ≥1 resulted in a lower rate of 10-year MACE outcomes (27% vs. 37%, adjusted p-value = 0.013).ConclusionsHigher levels of EPA, but not DHA, are associated with a lower risk of MACE. When combined with EPA, higher DHA blunts the benefit of EPA and is associated with a higher risk of MACE in the presence of low EPA. These findings can help explain the discrepant results of EPA-only and EPA/DHA mixed clinical supplementation trials

A new ratio for better predicting future death/myocardial infarction than standard lipid measurements in women &gt;50 years undergoing coronary angiography: the apolipoprotein A1 remnant ratio (Apo A1/ [VLDL3+IDL])

Abstract Background Women often lag behind men in their risk of cardiovascular events. However, with age and the onset of menopause, women’s cardiovascular risk eventually becomes similar to that of men. This change in risk may, in part, be attributable to a shift to a more atherogenic lipid profile. Our objective was to evaluate standard- and sub-lipid parameters and the apo A1 remnant ratio: (apo A1/[VLDL3-C+IDL-C]) for their associations with death/myocardial infarction among peri- and post-menopausal women. Methods Women (N=711) &gt;50 years of age undergoing coronary angiography were evaluated. Baseline clinical and angiographic characteristics, lipids, and sub-lipid levels (Vertical Auto Profile method) were collected. Cox regression analysis, adjusted by standard cardiovascular risk factors, was utilized to determine associations of lipid and sub-lipid tertiles(T) with death/myocardial infarction at 1 and 3 years. Results Patients averaged 67.7±9.4 years and 53.6% had underlying severe (≥70% stenosis) coronary artery disease. The apo A1 remnant ratio was found to have stronger associations for 1 year (T1 vs. T3: HR=2.13, p=0.03, T2 vs. T3: HR=1.57, p=0.21) and 3 year (T1 vs. T3: HR=2.32, p=0.002, T2 vs. T3: HR=1.97, p=0.01) death/myocardial infarction than any individual lipid (LDL-C, HDL-C, triglycerides, non-HDL-C) or sub-lipid (apo A1, apo B, VLDL3-C+IDL-C) measure, or any other well-known ratio (triglyercies/HDL-C, apo B/A1, TChol/HDL-C, HDL-C/[VLDL3-C+IDL-C]). Conclusions The apo A1 remnant ratio was a significant predictor of short and intermediate-term death/myocardial infarction risk among women &gt;50 years of age. Furthermore, this ratio was found to have greater predictive ability than traditional lipid and sub-lipid parameters and represents a potential new risk marker