Michos, Erin D.

BACKGROUND: Mortality due to ischemic heart disease (IHD) has declined in countries with high socioeconomic development. Whether these declines extend to other settings, and whether socioeconomic development influences IHD mortality among men and women differently, is unknown. METHODS: We obtained annual data on sex-specific IHD mortality rates for countries/territories in the GBD study (Global Burden of Disease) from 1980 to 2021. The sociodemographic index (SI), a measure of socioeconomic development, was retrieved for each country/territory. Age-adjusted IHD mortality rates were modeled as a smooth function of sex, year, and SI. RESULTS: From 1980 to 2021, IHD mortality rates did not decrease in low SI settings for men or women. In contrast, mortality rates relative to 1980 declined by >25% in average SI settings (age-adjusted mortality per 100 000, 153–107 for women and 218–161 for men) and >50% in high SI settings (age-adjusted mortality per 100 000, 162–69 for women and 258–114 for men). Comparing the 20th versus 80th percentile of SI in 2021 (corresponding to lower versus higher socioeconomic development), mortality rates were 81% higher for men and 111% higher for women living in socioeconomically deprived settings ( P for difference by sex: 0.01), although absolute differences were larger in men. The association of low SI with higher IHD mortality was especially pronounced for mortality attributable to environmental/occupational risk factors (eg, particulate matter air pollution, lead exposure, and extremes of temperature), with mortality rates being 174% higher among women and 199% higher among men. CONCLUSIONS: Across the past 4 decades, low socioeconomic development was associated with no improvement in IHD mortality rates for men or women, in contrast to the large reductions observed in settings with high socioeconomic development. In contemporary settings, socioeconomic deprivation is associated with larger relative excess mortality in women and larger absolute excess mortality in men.

Abstract Rationale Dysanapsis refers to a mismatch between airway tree caliber and lung size arising early in life. Dysanapsis assessed by computed tomography (CT) is evident by early adulthood and associated with chronic obstructive pulmonary disease (COPD) risk later in life. Objectives By examining the genetic factors associated with CT-assessed dysanapsis, we aimed to elucidate its molecular underpinnings and physiological significance across the lifespan. Methods We performed a genome-wide association study of CT-assessed dysanapsis in 11,951 adults, including individuals from two population-based and two COPD-enriched studies. We applied colocalization analysis to integrate genome-wide association study and gene expression data from whole blood and lung. Genetic variants associated with dysanapsis were combined into a genetic risk score that was applied to examine association with lung function in children from a population-based birth cohort (n = 1,278) and adults from the UKBiobank (n = 369,157). Measurements and Main Results CT-assessed dysanapsis was associated with genetic variants from 21 independent signals in 19 gene regions, implicating HHIP (hedgehog interacting protein), DSP, and NPNT as potential molecular targets based on colocalization of their expression. A higher dysanapsis genetic risk score was associated with obstructive spirometry among 5-year-old children and among adults in the fifth, sixth, and seventh decades of life. Conclusions CT-assessed dysanapsis is associated with variation in genes previously implicated in lung development, and dysanapsis genetic risk is associated with obstructive lung function from early life through older adulthood. Dysanapsis may represent an endophenotype link between the genetic variations associated with lung function and COPD.

Introduction: Remote monitoring using implantable cardioverter-defibrillators (ICDs) or cardiac resynchronization therapy defibrillator (CRT-D) can be used as an adjunctive diagnostic tool to traditional hospital and clinic visits to monitor the volume status of patients with heart failure (HF). Methods: We searched PubMed, Cochrane Library, and ClinicalTrials.gov (inception through February 4th, 2021) for randomized controlled trials (RCTs) evaluating ICDs/CRT-D remote monitoring versus standard of care in patients with HF. Of 642 articles retrieved after removing duplicate items, we included 11 RCTs encompassing 5,965 patients. Absolute risk difference (ARD) with 95% credible interval (CrI) was estimated. Pooled (posterior) risk difference was computed using Bayesian hierarchical methods, random effects model and weakly informative prior. Results: The ARD for mortality was centered at -0.01 (95%CrI: -0.03; 0.01, Tau: 0.02), with 82% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. The ARD for cardiovascular mortality was centered at -0.03 (95%CrI: -0.11; 0.05, Tau: 0.10), with 84% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0. The ARD for HF admissions was centered at -0.00 (95%CrI: -0.07; 0.06, Tau: 0.08), with 57% probability of ARD of ICD/CRT-D remote monitoring with respect to control being less than 0 [Figure]. Conclusions: This meta-analysis suggests that ICD/CRT-D remote monitoring in patients with HF is associated with a higher probability of reduced all-cause mortality, and cardiovascular mortality compared with standard care. However, ICD-CRT/D remote monitoring was associated with minimal probability of difference in HF hospitalizations.

Abstract Cardiovascular disease is the leading cause of death in women and men globally, with most due to atherosclerotic cardiovascular disease (ASCVD). Despite progress during the last 30 years, ASCVD mortality is now increasing, with the fastest relative increase in middle-aged women. Missed or delayed diagnosis and undertreatment do not fully explain this burden of disease. Sex-specific factors, such as hypertensive disorders of pregnancy, premature menopause (especially primary ovarian insufficiency), and polycystic ovary syndrome are also relevant, with good evidence that these are associated with greater cardiovascular risk. This position statement from the European Atherosclerosis Society focuses on these factors, as well as sex-specific effects on lipids, including lipoprotein(a), over the life course in women which impact ASCVD risk. Women are also disproportionately impacted (in relative terms) by diabetes, chronic kidney disease, and auto-immune inflammatory disease. All these effects are compounded by sociocultural components related to gender. This panel stresses the need to identify and treat modifiable cardiovascular risk factors earlier in women, especially for those at risk due to sex-specific conditions, to reduce the unacceptably high burden of ASCVD in women.

Introduction: Persons who conceived through Assisted Reproductive Technology (ART) have an increased risk of obstetric-associated complications. Hypothesis: ART is associated with increased acute cardiovascular (CV) complications during delivery admissions. Methods: We used data from the National Inpatient Sample (2008-2019) while utilizing ICD-9 or ICD-10 codes to identify delivery hospitalizations and ART procedure. Results: A total of 45,867,086 weighted delivery cases were identified, of which 0.24% were among individuals who conceived through ART (n=108,542). Persons with an ART history were older at the time of delivery (median 35 vs. 28 years, p<0.01) and had higher prevalence of hypertension, gestational diabetes, and dyslipidemia (all, p<0.01). After adjustment for age, race/ethnicity, comorbidities, multiple gestation, insurance, and income, ART remained an independent predictor of peripartum CV complications including preeclampsia (aOR 1.48 [1.45-1.51], p<0.01), heart failure (aOR 1.94 [1.10-3.40], p<0.01), and cardiac arrhythmias (aOR 1.39 [1.30-1.48], p<0.01) compared to natural conception. Likewise, the risk of acute kidney injury (aOR 2.57 [2.25-2.92], p<0.01), stroke (aOR 1.57 [1.23-2.01], p<0.01), pulmonary edema (aOR 2.29 [2.02-2.61], p<0.01), and venous thromboembolism (aOR 1.92 [1.63-2.25], p<0.01) were higher with ART. However, higher odds of developing peripartum cardiomyopathy or acute coronary syndrome were not associated with ART. Length of stay (3 vs. 2 days, p<0.01) and cost of hospitalization ($5,903 vs. $3,922, p<0.01) were higher for deliveries among persons with history of ART. Conclusions: Persons who conceived with ART had higher risk of preeclampsia, heart failure, cardiac arrhythmias, pulmonary edema, AKI, stroke, and VTE during their delivery hospitalizations. This may in part contribute to increased resource utilization seen in patients conceiving with ART

Introduction: Influenza infection is associated with increased cardiovascular morbidity and mortality. Many observational and clinical trials suggested that influenza vaccine can reduce cardiovascular outcomes. Methods: We searched EMBASE, PubMed, and Cochrane Library (inception through May 24th, 2022) for randomized controlled trials (RCTs) evaluating influenza vaccine and its association with cardiovascular outcomes. We used Mantel-Haenszel method with Paule-Mandel estimator of tau2 and Hartung-Knapp-Sidik-Jonkman adjustment (due to the small number of the included studies) to calculate the risk ratio (RR) and 95% confidence interval (CI). Results: Eight RCTs with a total of 14,420 patients were included in our analysis. Influenza vaccine as compared with control/placebo was associated with significantly lower risk of major adverse cardiovascular events (MACE) at follow-up [RR: 0.75; 95%CI: 0.57; 0.97; I2:56%] [Figure]. There was no significant difference between influenza vaccine and placebo/control in terms of all-cause mortality [RR: 0.84; 95%CI: 0.54; 1.33; I2:50%], cardiovascular mortality [RR: 0.77; 95%CI: 0.39; 1.50; I2:57%], or myocardial infarction [RR: 0.75; 95%CI: 0.52; 1.10; I2:0%]. Conclusion: Our meta-analysis suggests that influenza vaccine compared with control/placebo was associated with lower rates of MACE without a significant difference in the mortality or myocardial infarction rates.

Background Although there has been a decrease in the incidence of ST‐segment–elevation myocardial infarction (STEMI) in the United States, this trend might be stagnant or increasing in young women. We assessed the trends, characteristics, and outcomes of STEMI in women aged 18 to 55 years. Methods and Results We identified 177 602 women aged 18 to 55 with the primary diagnosis of STEMI from the National Inpatient Sample during years 2008 to 2019. We performed trend analyses to assess hospitalization rates, cardiovascular disease (CVD) risk factor profile, and in‐hospital outcomes stratified by three age subgroups (18–34, 35–44, and 45–55 years). We found STEMI hospitalization rates were decreased in the overall study cohort from 52 per 100 000 hospitalizations in 2008 to 36 per 100 000 in 2019. This was driven by decreased proportion of hospitalizations in women aged 45 to 55 years (74.2% to–71.7%; P <0.001). Proportion of STEMI hospitalizationincreased in women aged 18–34 (4.7%–5.5%; P <0.001) and 35–44 years (21.2%–22.7%; P <0.001). The prevalence of traditional and non‐traditional female‐specific or female‐predominant CVD risk factors increased in all age subgroups. The adjusted odds of in‐hospital mortality in the overall study cohort and age subgroups were unchanged throughout the study period. Additionally, we observed an increase in the adjusted odds of cardiogenic shock, acute stroke, and acute kidney injury in the overall cohort over the study period. Conclusions STEMI hospitalizations are increasing among women aged <45 years, and in‐hospital mortality has not changed over the past 12 years in women aged <55 years. Future studies on the optimization of risk assessment and management of STEMI in young women are urgently needed.

Various pharmacotherapies exist for heart failure with preserved ejection fraction (HFpEF), but with unclear comparative efficacy. We searched EMBASE, Medline, and Cochrane Library from inception through August 2021 for all randomized clinical trials in HFpEF (EF >40%) that evaluated beta-blockers, mineralocorticoid receptor antagonist (MRA), angiotensin-converting enzyme inhibitors (ACE), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and sodium-glucose cotransporter-2 inhibitors (SGLT2i). Outcomes assessed were cardiovascular mortality, all-cause mortality, and HF hospitalization. A frequentist network meta-analysis was performed with a random-effects model. We included 22 randomized clinical trials (30,673 participants; mean age = 71.7 ± 4.2 years; females = 49.3 ± 7.7%; median follow-up = 24.4 ± 11.1 months). Compared with placebo, there was no statistically significant difference in cardiovascular mortality [beta-blockers; odds ratio (OR) 0.79 (0.46–1.34), MRA; OR 0.90 (0.70–1.14), ACE OR 0.95 (0.59–1.53), ARB; OR 1.02 (0.87–1.19), ARNI; OR 0.97 (0.74–1.26) and SGLT2i; OR 1.00 (0.84–1.18)] or all-cause mortality [beta blockers; OR 0.75 (0.54–1.04), MRA; OR 0.90 (0.75–1.08) ACE; OR 1.05 (0.71–1.54), ARB; OR 1.03 (0.91–1.15), ARNI; OR 0.99 (0.82–1.20) and SGLT2i; OR 1.00 (0.89–1.13)]. The certainty in these estimates was low or very low. There was a significantly reduction in HF hospitalization with the use of SGLT2i [OR 0.71 (0.62–0.82), moderate certainty], ARNI [OR 0.77 (0.63–0.94), low certainty], and MRA [OR 0.81 (0.66–0.98), moderate certainty]; with corresponding P scores of 0.84, 0.68, and 0.58, respectively. In HFpEF, the use of beta-blockers, MRA, ACE/ARB/ARNI, or SGLT2i was not associated with improved cardiovascular or all-cause mortality. SGLT2i, ARNI, and MRA reduced the risk of HF hospitalizations.