Daily Cardiology Research Analysis

BACKGROUND: Aldosterone dysregulation contributes to hypertension. Lorundrostat is an aldosterone synthase inhibitor, but data on its efficacy and safety in patients with hypertension are limited. METHODS: In this multicenter, double-blind, randomized, placebo-controlled trial, we assigned participants who were receiving two to five antihypertensive medications and had a blood-pressure measurement of 140/90 mm Hg or higher obtained during an office visit to undergo a standardized antihypertensive regimen for 3 weeks. Subsequently, participants with an average 24-hour ambulatory blood pressure of 130/80 mm Hg or higher were assigned to receive placebo, lorundrostat at a stable dose of 50 mg daily (the stable-dose group), or lorundrostat at a starting dose of 50 mg daily, with an increase to 100 mg daily if systolic blood pressure was 130 mm Hg or higher after 4 weeks (the dose-adjustment group). The primary end point was the change in 24-hour average systolic blood pressure from baseline to week 12, assessed as the least-squares mean difference from placebo (the placebo-adjusted change) in each lorundrostat group. A key secondary end point was the change in 24-hour average systolic blood pressure from baseline to week 4, assessed as the placebo-adjusted change in the combined lorundrostat groups. RESULTS: A total of 285 participants underwent randomization; 94 were assigned to the stable-dose group, 96 to the dose-adjustment group, and 95 to the placebo group. The mean age was 60 years, and 150 participants (53%) were Black. After 12 weeks, the least-squares mean change in 24-hour average systolic blood pressure was -15.4 mm Hg in the stable-dose group, -13.9 mm Hg in the dose-adjustment group, and -7.4 mm Hg in the placebo group. The placebo-adjusted change in blood pressure was -7.9 mm Hg (97.5% confidence interval [CI], -13.3 to -2.6) in the stable-dose group and -6.5 mm Hg (97.5% CI, -11.8 to -1.2) in the dose-adjustment group. The placebo-adjusted change in 24-hour average systolic blood pressure from baseline to week 4 in the combined lorundrostat groups was -5.3 mm Hg (95% CI, -8.4 to -2.3). A potassium level above 6.0 mmol per liter occurred in 5 participants (5%) in the stable-dose group, 7 participants (7%) in the dose-adjustment group, and no participants in the placebo group. CONCLUSIONS: Lorundrostat was associated with greater reductions in 24-hour average blood pressure than placebo in participants with uncontrolled and treatment-resistant hypertension. (Funded by Mineralys Therapeutics; Advance-HTN ClinicalTrials.gov number, NCT05769608.).

IMPORTANCE: Most literature on the association between cardiovascular health (CVH) and incident cardiovascular disease (CVD) and mortality has relied on single midlife measurements. Understanding how cumulative CVH over time influences later-life CVD and mortality may aid early prevention. OBJECTIVE: To determine whether cumulative CVH, as measured by the American Heart Association Life's Essential 8 (LE8) from age 18 to 45 years, is associated with incident CVD and mortality in midlife. DESIGN, SETTING, AND PARTICIPANTS: This cohort study, the Coronary Artery Risk Development in Young Adults (CARDIA) study, collected CVH data for participants from 4 US centers from 1985 to 2020. Multivariate Cox proportional hazard models assessed the associations of (1) cumulative LE8 score by quartile, (2) cumulative LE8 score and score at age 45 years, and (3) cumulative LE8 score and LE8 score slope from age 18 to 45 years with incident CVD and mortality after age 45 years. MAIN OUTCOMES AND MEASURES: Incident CVD and all-cause mortality. Cumulative LE8 score was calculated as the area under the curve of the LE8 score (0-100, higher is better CVH) over time from age 18 to 45 years. RESULTS: There were 4832 CARDIA participants (2690 [55.7%] female and 2142 [44.3%] male) with a mean (SD) cumulative LE8 score from age 18 to 45 years of 2018.8 (95.0) point × years. Compared with quartile 1 (Q1, ie, lowest CVH), Q2, Q3, and Q4 had significantly lower hazards for CVD (Q2 HR, 0.44; 95% CI, 0.32-0.61; Q3 HR, 0.26; 95% CI, 0.18-0.38; Q4 HR, 0.12; 95% CI, 0.07-0.21) and mortality (Q2 HR, 0.51; 95% CI, 0.36-0.71; Q3 HR, 0.38; 95% CI, 0.26-0.55; Q4 HR, 0.29; 95% CI, 0.18-0.45) after age 45 years. When cumulative LE8 score from age 18 to 45 years and LE8 score at age 45 years were in the model together, both were significantly associated with lower risk for CVD. Likewise, both cumulative LE8 score and positive slope of (improving) LE8 score from age 18 to 45 years were significantly associated with lower hazards for incident CVD after age 45 years. CONCLUSIONS AND RELEVANCE: Greater cumulative CVH and improvement in CVH during young adulthood, as well as better CVH in middle age, were all independently associated with lower risk for incident CVD in midlife. These results emphasize the importance of maintaining and improving CVH throughout young adulthood.

AIMS: Patients with type 2 diabetes mellitus (T2DM) are at high risk for coronary artery disease (CAD) related events and are often asymptomatic. The role of cardiac imaging in screening asymptomatic T2DM patients remains controversial, as existing studies are limited by short follow-up periods. Therefore, study aim was to provide long-term (10 years) outcome data of T2DM patients screened with cardiac imaging. METHODS AND RESULTS: A total of 400 asymptomatic high-risk T2DM patients without history of CAD underwent screening with Single Photon Emission Computed Tomography (SPECT). Abnormal SPECT was defined as Summed Stress Score ≥ 4 or Summed Difference Score ≥ 2. Patients were followed for all-cause mortality and major adverse cardiovascular events (MACE, cardiovascular mortality + myocardial infarction).The mean age was 63 ± 8 years; 69% were male. Diabetic end-organ damage was present in 87% of patients. Baseline SPECT was abnormal in 22% of patients. Median follow-up was 11.1 (8.8, 12.8) years. Abnormal SPECT was associated with higher all-cause mortality [hazard ratio (HR) 1.614, P = 0.029] and MACE (HR 2.024, P = 0.009). A normal SPECT was associated with a significantly better prognosis (all-cause mortality 1.9 vs. 3.1%/year, P = 0.016; MACE 1.2 vs. 2.3%/year, P = 0.010). In the small subgroup of patients with abnormal SPECT, the treatment strategy (revascularization vs. conservative) had no effect on event-free survival. CONCLUSION: A normal SPECT was associated with an excellent long-term prognosis in high-risk T2DM patients. Hence, SPECT could serve as a valuable tool for advanced risk stratification in this population.