Despite highly effective contemporary treatment regimens, the majority of vascular events are not prevented, particularly in high-risk individuals.^1,2 Therefore, further strategies to decrease atherosclerosis burden and improve cardiovascular outcomes are needed. There is a strong inverse association between high-density lipoprotein (HDL) cholesterol and risk of coronary heart disease in epidemiological studies.^3,4

Aims Heart rate reduction is the cornerstone of the treatment of angina. The purpose of this study was to explore the prognostic value of heart rate in patients with stable coronary artery disease (CAD). Methods and results We assessed the relationship between resting heart rate at baseline and cardiovascular mortality/morbidity, while adjusting for risk factors. A total of 24 913 patients with suspected or proven CAD from the Coronary Artery Surgery Study registry were studied for a median follow-up of 14.7 years. All-cause and cardiovascular mortality and cardiovascular rehospitalizations were increased with increasing heart rate (P<0.0001). Patients with resting heart rate ≥83 bpm at baseline had a significantly higher risk for total mortality [hazard ratio (HR)=1.32, CI 1.19–1.47, P<0.0001] and cardiovascular mortality (HR=1.31, CI 1.15–1.48, P<0.0001) after adjustment for multiple clinical variables when compared with the reference group. When comparing patients with heart rates between 77–82 and ≥83 bpm with patients with a heart rate ≤62 bpm, the HR values for time to first cardiovascular rehospitalization were 1.11 and 1.14, respectively (P<0.001 for both). Conclusion Resting heart rate is a simple measurement with prognostic implications. High resting heart rate is a predictor for total and cardiovascular mortality independent of other risk factors in patients with CAD.

The ongoing worldwide increase in life expectancy portends a rising prevalence of age-related cardiovascular (CV) diseases in the coming decades that demands a deeper understanding of their molecular mechanisms. Inflammation has recently emerged as an important contributor for CV disease development. Indeed, a state of chronic sterile low-grade inflammation characterizes older organisms (also known as inflamm-ageing) and participates pivotally in the development of frailty, disability, and most chronic degenerative diseases including age-related CV and cerebrovascular afflictions. Due to chronic activation of inflammasomes and to reduced endogenous anti-inflammatory mechanisms, inflamm-ageing contributes to the activation of leucocytes, endothelial, and vascular smooth muscle cells, thus accelerating vascular ageing and atherosclerosis. Furthermore, inflamm-ageing promotes the development of catastrophic athero-thrombotic complications by enhancing platelet reactivity and predisposing to plaque rupture and erosion. Thus, inflamm-ageing and its contributors or molecular mediators might furnish targets for novel therapeutic strategies that could promote healthy ageing and conserve resources for health care systems worldwide. Here, we discuss recent findings in the pathophysiology of inflamm-ageing, the impact of these processes on the development of age-related CV diseases, results from clinical trials targeting its components and the potential implementation of these advances into daily clinical practice.

The COLchicine Cardiovascular Outcomes Trial (COLCOT) demonstrated the benefits of targeting inflammation after myocardial infarction (MI). We aimed to determine whether time-to-treatment initiation (TTI) influences the beneficial impact of colchicine. In COLCOT, patients were randomly assigned to receive colchicine or placebo within 30 days post-MI. Time-to-treatment initiation was defined as the length of time between the index MI and the initiation of study medication. The primary efficacy endpoint was a composite of cardiovascular death, resuscitated cardiac arrest, MI, stroke, or urgent hospitalization for angina requiring coronary revascularization. The relationship between endpoints and various TTI (<3, 4–7 and >8 days) was examined using multivariable Cox regression models. Amongst the 4661 patients included in this analysis, there were 1193, 720, and 2748 patients, respectively, in the three TTI strata. After a median follow-up of 22.7 months, there was a significant reduction in the incidence of the primary endpoint for patients in whom colchicine was initiated < Day 3 compared with placebo [hazard ratios (HR) = 0.52, 95% confidence intervals (CI) 0.32–0.84], in contrast to patients in whom colchicine was initiated between Days 4 and 7 (HR = 0.96, 95% CI 0.53–1.75) or > Day 8 (HR = 0.82, 95% CI 0.61–1.11). The beneficial effects of early initiation of colchicine were also demonstrated for urgent hospitalization for angina requiring revascularization (HR = 0.35), all coronary revascularization (HR = 0.63), and the composite of cardiovascular death, resuscitated cardiac arrest, MI, or stroke (HR = 0.55, all P < 0.05). Patients benefit from early, in-hospital initiation of colchicine after MI. COLCOT ClinicalTrials.gov number, NCT02551094.

Background—: Although a previous study has suggested that a genetic variant in the LPA region was associated with the presence of aortic valve stenosis (AVS), no prospective study has suggested a role for lipoprotein(a) levels in the pathophysiology of AVS. Our objective was to determine whether lipoprotein(a) levels and a common genetic variant that is strongly associated with lipoprotein(a) levels are associated with an increased risk of developing AVS. Methods and Results—: Serum lipoprotein(a) levels were measured in 17 553 participants of the European Prospective Investigation into Cancer (EPIC)-Norfolk study. Among these study participants, 118 developed AVS during a mean follow-up of 11.7 years. The rs10455872 genetic variant in LPA was genotyped in 14 735 study participants, who simultaneously had lipoprotein(a) level measurements, and in a replication study of 379 patients with echocardiography-confirmed AVS and 404 controls. In EPIC-Norfolk, compared with participants in the bottom lipoprotein(a) tertile, those in the top lipoprotein(a) tertile had a higher risk of AVS (hazard ratio, 1.57; 95% confidence interval, 1.02–2.42) after adjusting for age, sex, and smoking. Compared with rs10455872 AA homozygotes, carriers of 1 or 2 G alleles were at increased risk of AVS (hazard ratio, 1.78; 95% confidence interval, 1.11–2.87, versus hazard ratio, 4.83; 95% confidence interval, 1.77–13.20, respectively). In the replication study, the genetic variant rs10455872 also showed a positive association with AVS (odds ratio, 1.57; 95% confidence interval, 1.10–2.26). Conclusions—: Patients with high lipoprotein(a) levels are at increased risk for AVS. The rs10455872 variant, which is associated with higher lipoprotein(a) levels, is also associated with increased risk of AVS, suggesting that this association may be causal.

To evaluate the anti-anginal and anti-ischaemic efficacy of the selective I_f current inhibitor ivabradine in patients with chronic stable angina pectoris receiving beta-blocker therapy. In this double-blinded trial, 889 patients with stable angina receiving atenolol 50 mg/day were randomized to receive ivabradine 5 mg b.i.d. for 2 months, increased to 7.5 mg b.i.d. for a further 2 months, or placebo. Patients underwent treadmill exercise tests at the trough of drug activity using the standard Bruce protocol for randomization and at 2 and 4 months. Total exercise duration at 4 months increased by 24.3 ± 65.3 s in the ivabradine group, compared with 7.7 ± 63.8 s with placebo (P < 0.001). Ivabradine was superior to placebo for all exercise test criteria at 4 months (P < 0.001 for all) and 2 months (P-values between <0.001 and 0.018). Ivabradine in combination with atenolol was well tolerated. Only 1.1% of patients withdrew owing to sinus bradycardia in the ivabradine group. The combination of ivabradine 7.5 mg b.i.d. and atenolol at the commonly used dosage in clinical practice in patients with chronic stable angina pectoris produced additional efficacy with no untoward effect on safety or tolerability.