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Background: We evaluated whether early measurement of soluble urokinase plasminogen activator receptor (suPAR) could predict future risk of postoperative complications in initially asymptomatic patients with mild-moderate aortic stenosis (AS) undergoing aortic valve replacement (AVR) surgery., Methods: Baseline plasma suPAR levels were available in 411 patients who underwent AVR surgery during follow-up in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. Cox analyses were used to evaluate suPAR in relation to all-cause mortality and the composite endpoint of postoperative complications (all-cause mortality, congestive heart failure, stroke and renal impairment) occurring in the 30-day postoperative period., Results: Patients with initially higher levels of suPAR were at increased risk of postoperative mortality with a HR of 3.5 (95% CI 1.4 to 9.0, P=0.008) and postoperative complications with a HR of 2.7 (95% CI 1.5 to 5.1, P=0.002), per doubling in suPAR. After adjusting for the European System for Cardiac Operative Risk Evaluation or Society of Thoracic Surgeons risk score, suPAR remained associated with postoperative mortality with a HR 3.2 (95% CI 1.2 to 8.6, P=0.025) and 2.7 (95% CI 1.0 to 7.8, P=0.061); and postoperative complications with a HR of 2.5 (95% CI 1.3 to 5.0, P=0.007) and 2.4 (95% CI 1.2 to 4.8, P=0.011), respectively., Conclusion: Higher baseline suPAR levels are associated with an increased risk for postoperative complications and mortality in patients with mild-moderate, asymptomatic AS undergoing later AVR surgery. Further validation in other subsets of AS individuals are warranted., Trial Registration Number: NCT00092677; Post-results., Competing Interests: Competing interests: JEO is a co-founder and shareholder of ViroGates A⁄S, Denmark, the company that produces the suPARnostic assay. He is a co-inventor on patents on suPAR and risk. Copenhagen University Hospital Hvidovre, Denmark, owns the patents, which are licensed to ViroGates A⁄S. KB, SR, AYK and KW served on the SEAS Steering Committee were investigators and members of the steering committees of the SEAS study and have received honoraria from Merck & Co, the sponsor of the SEAS study. KB, SR and KW have received grant support from Merck & Co, the sponsor of the SEAS study. AYK reported Speaker’s fee from Abbott, MSD and Novo Nordisk, Consult for MSD, research funding from MSD and ownership of Orion Pharma stock.

Background: Single living has been associated with a worse prognosis of acute coronary syndrome (ACS). We aimed to study the relation of sociodemographic characteristics to the morbidity, mortality, and case fatality (CF) of ACS in a large population-based ACS register., Methods: The population-based FINAMI myocardial infarction register recorded 15,330 cases of ACS among persons aged 35-99 years in Finland in 1993-2002. Record linkage with the files of Statistics Finland provided information on sociodemographic characteristics (marital status, household size)., Results: ACS incidence and 28-day mortality rate were higher in unmarried men and women in all age groups. The prehospital CF of incident ACS was higher in single living and/or unmarried 35-64-year-old people. The 28-day CF was 26% (95% confidence interval, CI, 24-29%) in married men, 42% (95% CI 37-47%) in men who had previously been married, and 51% (95% CI 46-57%) in never-married men. Among women, the corresponding figures were 20% (95% CI 15-24%), 32% (95% CI 25-39%), and 43% (95% CI 31-56%). Most of these CF differences were apparent already at the prehospital phase. The only difference in treatment was that middle-aged men living alone or unmarried received thrombolysis less often. The disparities in ACS morbidity and mortality by marital status tended to widen during the study period., Conclusions: Single living and/or being unmarried increases the risk of having a heart attack and worsens its prognosis both in men and women regardless of age. Most of the excess mortality appears already before the hospital admission and seems not to be related to differences in treatment of ACS., (© The European Society of Cardiology 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To examine the changes in socioeconomic disparities in the incidence of coronary heart disease (CHD) and mortality in Finland and to analyze the effects of the severe economic recession of the early 1990s on these disparities., Methods: The population-based FINAMI Myocardial Infarction (MI) register recorded all suspected MI events among men and women ages 35 to 99 years in four geographical areas of Finland. Record linkage with the files of Statistics Finland provided us with detailed information on the indicators of socioeconomic status (SES; income, education, and profession). Rates were expressed per 100,000 inhabitants of each socioeconomic group per year and age-standardized to the European standard population. Poisson regression was used for analyzing rate ratios and time trends of coronary events in different socioeconomic groups., Results: The mortality rate ratio of coronary events among 35- to 64 year-old men was 5.21 (95% confidence interval, 4.23-6.41) when the lowest income sixth to the highest income sixth were compared. Among women, the respective rate ratio was 11.13 (5.77-21.45). Significant differences in the incidence and 28-day mortality by SES were seen also in the older age groups. Some socioeconomic differences were found in the proportions of patients receiving thrombolysis or undergoing early revascularization. No substantial changes were observed in inequalities between the socioeconomic groups during the study period., Conclusions: The excess CHD morbidity and mortality among persons with lower SES is still considerable in Finland, but the economic recession did not widen the differences., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Low heart rate (HR) variability is associated with increased risk of cardiovascular morbidity and mortality, but the causes and mechanisms of this association are not well known. This prospective study was designed to test the hypothesis that reduced HR variability is related to progression of coronary atherosclerosis. Average HR and HR variability were analyzed in 12-hour ambulatory ECG recordings from 265 qualified patients participating in a multicenter study to evaluate the angiographic progression of coronary artery disease in patients with prior coronary artery bypass surgery and low high-density lipoprotein cholesterol concentrations (<1.1 mmol/L). Participants were randomized to receive a placebo or gemfibrozil therapy. The progression of coronary atherosclerosis was estimated by quantitative, computer-assisted analysis of coronary artery stenoses from the baseline angiograms and from repeated angiograms performed an average of 32 months later. The progression of focal coronary atherosclerosis of the patients randomized to placebo therapy was more marked in the tertile with the lowest standard deviation of all normal to normal R-R intervals (SDNN, 74+/-13 ms; mean decrease in the per-patient minimum luminal diameter -0.17 mm; 95% confidence interval [CI], -0.23 to -0.12 mm) than in the middle tertile (SDNN, 107+/-7 ms; mean decrease -0.05 mm; 95% CI, -0.08 to -0.01 mm) or highest tertile (SDNN, 145+/-25 ms; mean change 0.01 mm; 95% CI, -0. 04 to 0.02 mm) (P<0.001 between the tertiles). This association was abolished by gemfibrozil. SDNN was lower (P<0.001) and minimum HR was faster (P<0.01) in the patients with marked progression than in those with regression of focal coronary atherosclerosis. In multiple regression analysis including HR variability, minimum HR, demographic and clinical variables, smoking, blood pressure, glucose, lipid measurements and lipid-modifying therapy, progression of focal coronary atherosclerosis was independently predicted by the SDNN (beta=0.24; P=0.0001). Low HR variability analyzed from ambulatory ECG predicts rapid progression of coronary artery disease. HR variability provided information on progression of focal coronary atherosclerosis beyond that obtained by traditional risk markers of atherosclerosis.