Journal of the American College of Cardiology最新文献

Background: Atrial fibrillation (AF) is heritable and its complex underlying genetic substrate is gradually being unraveled.

Objectives: We sought to explore the impact of disease-causing cardiomyopathy variants on the risk of AF after adjustment for incident ventricular cardiomyopathy and clinical heart failure in 2 cohort studies (UK Biobank [UKB] and All of Us [AoU]) and evaluate the utility of polygenic risk scores (PRS) to further discern the risk of atrial and ventricular phenotypes in carriers.

Methods: Cox regression was used to evaluate for associations between disease-causing variants within genes for 3 cardiomyopathies (dilated cardiomyopathy [DCM], hypertrophic cardiomyopathy [HCM], and arrhythmogenic right ventricular cardiomyopathy) and AF. Disease-specific PRSs for AF, DCM, and HCM stratified study participants into quintiles. A HR random-effects meta-analysis was performed using the DerSimonian-Laird method. The Kaplan-Meier method was used to ascertain cumulative incidence from birth to 75 years of age.

Results: Among 655,796 individuals from UKB and AoU, presence of a disease-causing variant was associated with an increased AF hazard (HR: 1.73; 95% CI: 1.59-1.89; P < 0.001), including after adjustment for incident ventricular cardiomyopathy or clinical heart failure (adjusted to HR: 1.55; 95% CI: 1.46-1.64, P < 0.001). The cumulative AF risk for study participants with a putative disease-causing rare variant and a PRS_AF within the top-risk quintile ranged from 32.5% (UKB) to 32.4% (AoU) relative to 9.8% (UKB) and 11.0% (AoU) for individuals without a putative disease-causing variant and a PRS_AF within the lowest-risk quintile. The absolute cumulative cardiomyopathy risk among study participants with both a putative disease-causing variant and a disease-specific PRS within the top-risk quintile ranged from 5.9% (UKB) to 15.2% (AoU) for DCM and from 11.7% (UKB) to 19.1% (AoU) for HCM.

Conclusions: Genetic variants that cause cardiomyopathy also increase the risk of AF, even in individuals without heart failure or overt ventricular disease. Combining disease-specific PRSs with these variants helps identify whether a person is more likely to develop atrial or ventricular disease. Although discovered as causes of cardiomyopathy, these genes often have an equal or greater impact on the risk of AF.

Background: Poorer cardiovascular outcomes among ethnic minorities have been reported, particularly during the COVID-19 pandemic. However, the relationship between ethnicity and quality of care after hospitalization for heart failure (HF) and long-term outcomes is largely unknown.

Objectives: The aim of this analysis is to investigate quality of care and longer-term outcomes of patients hospitalized with acute HF according to ethnicity.

Methods: Routinely collected data for England from the National Heart Failure Audit, National Health Service Hospital Episode Statistics, and Office for National Statistics death register from 2018 to 2023 were used to investigate the quality of care and outcomes after hospitalization with HF according to ethnicity.

Results: National Heart Failure Audit data for 239,890 patients admitted with HF were grouped by ethnicity as White (215,800), Black (6,610), Asian (12,940), and mixed/other (4,540), with median ages of 81 years (IQR: 73-88 years),75 years (IQR: 60-84 years), 77 years (IQR: 67-84 years), and 75 years (IQR: 61-84 years), respectively. Overall, patients had a median of 3 comorbidities (IQR: 2-4 comorbidities), with Asians having the greatest number. About 50% of patients had HF with reduced ejection fraction in all ethnic groups. For HF with reduced ejection fraction, White patients were least likely to be discharged on guideline-recommended therapies. Over a median follow-up of 68 weeks (IQR: 20-142 weeks), 122,980 (57%) White patients died, as did 2,860 (43%) Black patients, 6,270 (48%) Asian patients, and 1,900 (42%) patients of other/mixed ethnicity. About 90% of deaths were due to cardiovascular or respiratory causes. After adjusting for age, sex, socioeconomic factors, and variables associated with HF severity, all ethnic groups had lower mortality compared with White patients, including those who were Black (HR: 0.81; 95% CI: 0.78-0.84), Asian (HR: 0.77; 95% CI: 0.75-0.79), or from mixed/other ethnic groups (HR: 0.72; 95% CI: 0.69-0.75).

Conclusions: In a universal health care system, treating an ethnically diverse population hospitalized for HF, non-White patients received better pharmacological management, which was associated with better long-term outcomes.

Background: The utility of coronary artery calcium (CAC) scoring in individuals with elevated lipoprotein(a) [Lp(a)] for atherosclerotic cardiovascular disease (ASCVD) risk assessment is currently unclear given the propensity of Lp(a) toward noncalcified plaque.

Objectives: The authors aimed to evaluate the interaction between elevated Lp(a) (>50 mg/dL) and CAC score, and the association of Lp(a) with ASCVD risk across strata of CAC.

Methods: A pooled cohort of participants without known ASCVD from 4 U.S.-based prospective cohort studies with baseline Lp(a) and CAC measurements was used. The association between elevated Lp(a) across CAC strata and incident ASCVD (myocardial infarction, stroke, coronary revascularization) was evaluated in multivariable Cox regression models.

Results: The study included 11,319 participants (mean age 56 years, 54% women) with 1,569 incident ASCVD events over 14.8 year mean follow-up. Lp(a) >50 mg/dL (HR: 1.24; 95% CI: 1.09-1.41) and CAC >0 (HR: 2.44; 95% CI: 2.14-2.77) were independently associated with ASCVD risk (P interaction = 0.80). Among individuals with CAC = 0, ASCVD incidence rates were low overall, but higher with Lp(a) >50 mg/dL vs ≤50 mg/dL (4.9 vs 3.8/1,000 person-years, HR: 1.28; 95% CI: 1.01-1.60). Among those with CAC >0, increased risk was again noted with elevated Lp(a) (21.2 vs 18.2/1,000 person-years, HR: 3.03; 95% CI: 2.52-3.64). Similar results were observed when examining further CAC strata with the greatest risk noted with both CAC ≥300 and Lp(a) >50 mg/dL (HR: 6.12; 95% CI: 4.80-7.81). Consistent results were noted by age and sex with greater absolute risk in general among individuals >50 years of age and men.

Conclusions: Elevated Lp(a) is associated with higher relative risk across CAC strata, including CAC of 0. Among individuals with CAC of 0, absolute event rates remain low even when Lp(a) is elevated. CAC scoring remains a powerful tool for risk assessment among individuals with elevated Lp(a).