Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.

Abstract-In the HOPE-trial, the ACE inhibitor ramipril significantly reduced cardiovascular morbidity and mortality in patients at high risk for cardiovascular events. The benefit could only partly be attributed to the modest mean reduction of office blood pressure (OBP) during the study period (3/2 mm Hg). However, because according to the HOPE protocol ramipril was given once daily at bedtime and blood pressure was measured during the day, the 24-hour reduction of blood pressure may be underestimated based on OBP. Thirty-eight patients with peripheral arterial disease enrolled in the HOPE study underwent 24-hour ambulatory blood pressure (ABP) measurement before randomization and after 1 year. OBP was measured in the sitting position immediately before fitting the ABP measuring equipment to the patients. Ramipril did not significantly reduce OBP (8/2 mm Hg, PϭNS) or day ABP (6/2 mm Hg, PϭNS) after 1 year. Twenty-four-hour ABP was significantly reduced (10/4 mm Hg, Pϭ0.03), mainly because of a more pronounced blood pressure lowering effect during nighttime (17/8 mm Hg, PϽ0.001). The night/day ratio was also significantly lowered in the ramipril group. ABP shows greater falls, especially at night, than OBP during treatment with ramipril given once daily at bedtime. Although, OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies, the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may, to a larger extent than previously ascribed, relate to effects on blood pressure patterns over the 24-hour period.(Hypertension. 2001;38:e28-e32.)

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Background: The comparative efficacy and safety of ticagrelor vs. clopidogrel in older myocardial infarction (MI) patients has received limited study. Methods: We performed an observational analysis of all patients ≥80 years (n=14005) who were discharged alive with aspirin combined with either clopidogrel (60.2%) or ticagrelor (39.8%) after a MI between 2010 and 2017 registered in the national registry Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART). Inverse probability treatment weighting was used in Cox regression models to adjust for differences in demographics, in-hospital therapies, and medications. The primary ischemic outcome (death, MI or stroke), and bleeding were obtained from national registries at 1 year. A sensitivity analysis in <80-year-old patients was performed. Results: In patients ≥80 years, the incidence of the primary ischemic outcome (HR 0.97, 95% CI 0.88-1.06) was similar for ticagrelor- and clopidogrel-treated patients. Ticagrelor was associated with a 17% and 48% higher risk of death (1.17 (1.03- 1.32)) and bleeding (1.48 (1.25- 1.76)), but a lower risk of MI (0.80 (0.70- 0.92)) and stroke (0.72 (0.56-0.93)). In <80-year-old patients the incidence of the primary ischemic outcome was 17% (0.83 (0.77-0.89)) lower with ticagrelor. Ticagrelor was associated with 15% (0.85 (0.76-0.96)) lower risk of death, 32% higher risk of bleeding (1.32 (1.18-1.47)), but lower risk of MI (0.82 (0.75-0.91)) and stroke (0.82 (0.69-0.98)). Conclusions: Ticagrelor use among elderly MI patients was associated with higher risk of bleeding and death compared with clopidogrel. A randomized study of ticagrelor vs clopidogrel in the elderly is needed.