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Background: The cardiovascular (CV) safety in terms of heart failure among different classes of treatment remains largely unknown. We sought to assess the comparative effect of these agents on heart failure outcomes. Methods:This study was registered in the International Prospective Register of Systematic Reviews (CRD 42016042063). MEDLINE, EMBASE, and the Cochrane Library Central Register of Controlled Trials were searched. For the primary outcomes reported previously, studies between Jan 1, 1980 and June 30, 2016 were screened, and subsequently updated till Jan 24, 2019. We performed network meta-analysis to obtain estimates for the outcomes of heart failure, in particular by rankograms for ranking of heart failure risk as well as by pairwise comparisons among all classes of anti-diabetic medications.Results: A total of 91 trials were included, among which were 171,253 participants and 4163 reported cases of heart failure events. As for rankograms, the surface under the cumulative ranking curves (SUCRA) of sodium-glucose co-transporters 2 and thiazolidinediones were 93.4% and 4.3%, respectively, signifying the lowest and highest risk of heart failure, respectively. As for pairwise comparisons in the network, sodium-glucose co-transporters 2 were significantly superior to insulin (OR: 0.75, 95% CI 0.62-0.91), dipeptidyl peptidase 4 inhibitors (OR: 0.68, 95% CI 0.59-0.78), glucagon-like peptide-1 receptor agonists (OR: 0.65, 95% CI 0.54-0.78), and thiazolidinediones (OR: 0.46, 95% CI 0.27-0.77) in terms of heart failure risk. Furthermore, in an exploratory analysis among subjects with underlying heart failure or at risk of heart failure, the superiority of sodium-glucose co-transporters 2 was still significant. Conclusions:In terms of heart failure risk, sodium-glucose co-transporters 2 were the most favorable option among all classes of anti-diabetic medications.

Background Hypertensive patients are highly heterogeneous in cardiovascular prognosis and treatment responses. A better classification system with phenomapping of clinical features would be of greater value to identify patients at higher risk of developing cardiovascular outcomes and direct individual decision-making for antihypertensive treatment. Methods An unsupervised, data-driven cluster analysis was performed for all baseline variables related to cardiovascular outcomes and treatment responses in subjects from the Systolic Blood Pressure Intervention Trial (SPRINT), in order to identify distinct subgroups with maximal within-group similarities and between-group differences. Cox regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular outcomes and compare the effect of intensive antihypertensive treatment in different clusters. Results Four replicable clusters of patients were identified: cluster 1 (index hypertensives); cluster 2 (chronic kidney disease hypertensives); cluster 3 (obese hypertensives) and cluster 4 (extra risky hypertensives). In terms of prognosis, individuals in cluster 4 had the highest risk of developing primary outcomes. In terms of treatment responses, intensive antihypertensive treatment was shown to be beneficial only in cluster 4 (HR 0.73, 95% CI 0.55–0.98) and cluster 1 (HR 0.54, 95% CI 0.37–0.79) and was associated with an increased risk of severe adverse effects in cluster 2 (HR 1.18, 95% CI 1.05–1.32). Conclusion Using a data-driven approach, SPRINT subjects can be stratified into four phenotypically distinct subgroups with different profiles on cardiovascular prognoses and responses to intensive antihypertensive treatment. Of note, these results should be taken as hypothesis generating that warrant further validation in future prospective studies.

To investigate the optimal blood pressure (BP) in patients with coronary artery disease (CAD), we conducted subgroup analysis using SPRINT data. The study sample included 1206 participants with CAD (of whom 692 underwent coronary revascularization) and 8127 participants without CAD. Participants were randomized into two groups (systolic BP target of 140 mm Hg vs. 120 mm Hg). The primary outcome was a composite of cardiovascular events. After a median follow-up of 3.9 years, the hazard ratios (HRs) for the primary outcome were 0.65 (95% confidence interval (CI) 0.53–0.79) and 1.05 (95% CI 0.76–1.46) among those in the non-CAD and CAD subgroups, respectively (P value for interaction 0.02). Intensive BP treatment was a protective factor for all-cause death (HR 0.60, 95% CI 0.37–0.96) in the CAD subgroup, compared with standard BP treatment. The HRs (95% CI) for stroke were 3.57 (1.17–10.85) and 1.03 (0.29–3.62) among those in the coronary revascularization and non-revascularization subgroups, respectively (P value for interaction 0.13). For safety events, intensive BP treatment increased the risk of hypotension (HR 2.00, 95% CI 1.06–3.79) and electrolyte abnormalities (HR 2.38, 95% CI 1.25–4.56) in the CAD subgroup, while the risk of serious adverse events did not increase (HR 1.03, 95% CI 0.88–1.20). These results suggest that positive benefits from intensive BP treatment might be attenuated in patients with CAD who are under better secondary prevention. The risk of stroke might increase at the systolic BP target of 120 mm Hg in case of coronary revascularization, although the confidence interval was wide.

Background The influences of low‐carbohydrate diets in cardiovascular disease are controversial. Few studies have examined the relationship of carbohydrate intake and risk of incident atrial fibrillation ( AF ). We aimed to evaluate the association between carbohydrate intake and the risk of incident AF in the ARIC (Atherosclerosis Risk in Communities) Study. Methods and Results We included 13 385 participants (age, 54.2±5.8 years; 45.1% men and 74.7% white) who completed a dietary questionnaire at baseline (1987–1989) in the ARIC Study. The primary outcome was incident AF , which was identified by ECG performed during study examinations, hospital discharge codes, and death certificates. We used multivariable Cox hazard regression models to assess the association between carbohydrate intake and incident AF . We further explored the effects of specific food source (animal versus plant based) used to replace carbohydrate intake in the low‐carbohydrate intake setting. During a median follow‐up of 22.4 years, 1808 cases (13.5%) of AF occurred. The hazard ratio for incident AF associated with a 1‐ SD (9.4%) increase in carbohydrate intake as a percentage of energy intake was 0.82 (95% CI , 0.72–0.94), after adjustment for traditional AF risk factors and other diets factors. Results were similar when individuals were categorized by carbohydrate intake quartiles (hazard ratio, 0.64; 95% CI , 0.49–0.84; comparing extreme quartiles). No association was found between the type of protein or fat used to replace the carbohydrate and risk of incident AF . Conclusions Low‐carbohydrate diets were associated with increased risk of incident AF , regardless of the type of protein or fat used to replace the carbohydrate.

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Background The association between blood pressure control and clinical outcomes is unclear among patients with heart failure with preserved ejection fraction. Both too high and too low of systolic blood pressure (SBP) have been reported to be related to poor clinical prognosis. This study aimed to assess the association between time in SBP target range and adverse clinical events among patients with heart failure with preserved ejection fraction. Methods and Results This study was a secondary analysis of the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist) trial, a randomized clinical trial that compared the efficacy and safety of spironolactone in patients with heart failure with preserved ejection fraction. Time in target range (TTR) was calculated using linear interpolation, with the target range of SBP defined as 110 to 130 mm Hg. The association between TTR with adverse outcomes was estimated using multivariable Cox regression to adjust for multiple confounders. Participants with greater TTR were younger, more likely to be White, had less comorbidities, and lower body mass index. After adjusting for multiple covariates including mean SBP, 1‐SD increment (38.3%) of TTR was significantly associated with a decreased risk of primary composite end point (hazard ratio [HR], 0.81 [0.73–0.90]), as well as a lower risk of all‐cause mortality (HR, 0.81 [0.73–0.90]), cardiovascular death (HR, 0.78 [0.68–0.90]), and heart failure hospitalization (HR, 0.85 [0.74–0.97]). Results were similar when participants were categorized by TTR groups. Subgroup analyses showed that the associations were more significant in young people than in the old ( P interaction =0.028). Conclusions In patients with heart failure with preserved ejection fraction, greater time in SBP target range was statistically associated with a decreased risk of cardiovascular outcomes and mortality events beyond blood pressure level, especially among younger patients.

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