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To evaluate the association between trimethylamine N-oxide (TMAO) and related metabolites with adverse cardiovascular events in a multiethnic urban primary prevention population.

Previous meta-analyses of summary data from randomised controlled trials have shown that statin therapy increases the risk of diabetes, but less is known about the size or timing of this effect, or who is at greatest risk. We aimed to address these gaps in knowledge through analysis of individual participant data from large, long-term, randomised, double-blind trials of statin therapy.

BackgroundTreating obesity may be a pathway to prevent and control hypertension. In the SURMOUNT-1 trial in people with obesity or overweight with weight-related complications, 72-week tirzepatide treatment led to clinically meaningful body weight and blood pressure reduction. Post hoc analyses were conducted to further explore the effects of tirzepatide on the pattern of blood pressure reduction and whether the effects were consistent across various subgroups.MethodsThe mixed effect for repeated measure model was used to compare changes in overall blood pressure, across demographic and clinical subgroups, baseline blood pressure subgroups and hypertension categories between SURMOUNT-1 participants randomised to treatment with tirzepatide and placebo. The association between weight changes and blood pressure and adverse events associated with low blood pressure were also evaluated by mediation analysis.ResultsTirzepatide treatment was associated with a rapid decline in systolic and diastolic blood pressure over the first 24 weeks, followed by blood pressure stabilisation until the end of the observation period, resulting in a significant net reduction by 72 weeks of 6.8 mm Hg systolic and 4.2 mm Hg diastolic blood pressure versus placebo. Participants randomly assigned to any tirzepatide group were more likely than those assigned to placebo to have normal blood pressure at week 72 (58.0% vs 35.2%, respectively). The effects were broadly consistent across baseline blood pressure subgroups, shifting the blood pressure distribution curve to lower blood pressure levels. The mediation analysis indicated that weight loss explained 68% of the systolic and 71% of the diastolic blood pressure reduction. Low blood pressure adverse events were infrequent, but the rate was higher in the tirzepatide group.ConclusionsIn these post hoc analyses, in participants with obesity or overweight, tirzepatide was associated with reduced blood pressure consistently across participant groups primarily via weight loss, with relatively few blood pressure-related adverse events.Trial registration numberNCT04184622.

The recent heart failure (HF) guideline recommends the inclusion of cardiac biomarkers in defining Stage B HF.

Statin therapy is effective for the prevention of atherosclerotic cardiovascular disease and is widely prescribed, but there are persisting concerns that statin therapy might frequently cause muscle pain or weakness. We aimed to address these through an individual participant data meta-analysis of all recorded adverse muscle events in large, long-term, randomised, double-blind trials of statin therapy.

Background: Oxidative stress and inflammation are crucial in atherogenesis, [alpha]-Tocopherol is both an antioxidant and an anti-inflammatory agent. Objective: We evaluated the effect of RRR-[alpha]-tocopherol supplementation on carotid atherosclerosis in patients with stable coronary artery disease (CAD) on drug therapy. Design: Randomized, controlled, double-blind trial compared RRR-[alpha]-tocopherol (1200 IU/d for 2 y) with placebo in 90 patients with CAD. Intimal medial thickness (IMT) of both carotid arteries was measured by high-resolution B-mode ultrasonography at 0, 1, 1.5, and 2 y. At 6-mo intervals, plasma [alpha]-tocopherol concentrations, C-reactive protein (CRP), LDL oxidation, monocyte function (superoxide anion release, cytokine release, and adhesion to endothelium), and urinary [F.sub.2]-isoprostanes were measured. Results: [alpha]-Tocopherol concentrations were significantly higher in the [alpha]-tocopherol group but not in the placebo group. High-sensitivity CRP concentrations were significantly lowered with [alpha]-tocopherol supplementation than with placebo (32%; P < 0.001). [alpha]-Tocopherol supplementation significantly reduced urinary [F.sub.2]-isoprostanes (P < 0.001) and monocyte superoxide anion and tumor necrosis factor release compared with baseline and placebo (P < 0.001). No significant difference was observed in the mean change in total carotid IMT in the placebo and [alpha]-tocopherol groups. In addition, no significant difference in cardiovascular events was observed (P = 0.21). Conclusions: High-dose RRR-[alpha]-tocopherol supplementation in patients with CAD was safe and significantly reduced plasma biomarkers of oxidative stress and inflammation but had no significant effect on carotid IMT during 2 y. Am J Clin Nutr 2007;86:1392-8. KEY WORDS Vitamin E, atherosclerosis, coronary artery disease, inflammation, oxidative stress, intimal media thickness, carotid

Novel approaches to the assessment of kidney disease risk during hypertension treatment are needed because of the uncertainty of how intensive blood pressure (BP) lowering impacts kidney outcomes. We determined whether longitudinal N-terminal pro–B-type natriuretic peptide (NT–proBNP) measurements during hypertension treatment are associated with kidney function decline.

This study evaluated the association of transthyretin (TTR) gene variant, in which isoleucine substitutes for valine at position 122 (V142I), with cardiac structure, function, and heart failure (HF) risk among middle-aged Black adults.

IMPORTANCE: Elevated high-sensitivity cardiac troponin T (hscTnT) and N-terminal pro–B-type natriuretic peptide (NTproBNP) levels are associated with risk of heart failure (HF) and mortality among individuals in the general population. However, it is unknown if this risk is modifiable. OBJECTIVE: To test the hypothesis that elevated hscTnT and NTproBNP levels would identify individuals with the greatest risk for mortality and HF and the largest benefit associated with intensive systolic blood pressure (SBP) lowering. DESIGN, SETTING, AND PARTICIPANTS: This is a nonprespecified post hoc analysis of the multicenter, prospective, randomized clinical Systolic Blood Pressure Intervention Trial (SPRINT), conducted from October 20, 2010, to August 20, 2015. A total of 9361 patients without diabetes with increased risk for cardiovascular disease were randomized to receive intensive vs standard SBP lowering. Statistical analysis was performed on an intention-to-treat basis from September 30, 2019, to July 29, 2021. INTERVENTIONS: Participants were randomized to undergo intensive (&lt;120 mm Hg) or standard (&lt;140 mm Hg) SBP lowering. High-sensitivity cardiac troponin T and NTproBNP levels were measured from stored specimens collected at enrollment, with elevated levels defined as 14 ng/L or more for hscTnT (to convert to micrograms per liter, multiply by 0.001) and 125 pg/mL or more for NTproBNP (to convert to nanograms per liter, multiply by 1.0). MAIN OUTCOMES AND MEASURES: The primary outcome of this ancillary study was HF and mortality. RESULTS: Of the 9361 participants enrolled in SPRINT, 8828 (5578 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured hscTnT levels and 8836 (5585 men [63.2%]; mean [SD] age, 68.0 [9.5] years) had measured NTproBNP levels; 2262 of 8828 patients (25.6%) had elevated hscTnT levels, 3371 of 8836 patients (38.2%) had elevated NTproBNP, and 1411 of 8828 patients (16.0%) had both levels elevated. Randomization to the intensive SBP group led to a 4.9% (95% CI, 1.7%-7.5%) absolute risk reduction (ARR) over 4 years in death and HF (421 events) for those with elevated hscTnT and a 1.7% (95% CI, 0.7%-2.5%) ARR for those without elevated levels. Similarly, for those with elevated NTproBNP, the ARR for death and HF over 4 years was 4.6% (95% CI, 2.3%-6.5%) vs 1.8% (95% CI, 0.9%-2.5%) in those without elevated levels. For those with elevated levels of both biomarkers, the ARR for death and HF over 4 years was 7.8% (95% CI, 3.3%-11.3%) vs 1.7% (95% CI, 0.8%-2.3%) in those with neither biomarker elevated. No significant treatment group by biomarker category interactions were detected. CONCLUSIONS AND RELEVANCE: Intensive SBP control led to large absolute differences in death and HF among patients with abnormal hscTnT and NTproBNP levels. These findings demonstrate that risk associated with elevation of these biomarkers is modifiable with intensive BP control. A prospective, randomized clinical trial is needed to evaluate whether these biomarkers may help guide selection of patients for intensive SBP lowering. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01206062

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OBJECTIVE--To determine the association between circulating soluble receptor for advanced glycation end products (sRAGE) and coronary atherosclerosis. RESEARCH DESIGN AND METHODS--Using data from the Dallas Heart Study, a probability-based population [...]

IMPORTANCE: Human genetics and studies in experimental models support a key role of monocyte-chemoattractant protein–1 (MCP-1) in atherosclerosis. Yet, the associations of circulating MCP-1 levels with risk of coronary heart disease and cardiovascular death in the general population remain largely unexplored. OBJECTIVE: To explore whether circulating levels of MCP-1 are associated with risk of incident coronary heart disease, myocardial infarction, and cardiovascular mortality in the general population. DATA SOURCES AND SELECTION: Population-based cohort studies, identified through a systematic review, that have examined associations of circulating MCP-1 levels with cardiovascular end points. DATA EXTRACTION AND SYNTHESIS: Using a prespecified harmonized analysis plan, study-specific summary data were obtained from Cox regression models after excluding individuals with overt cardiovascular disease at baseline. Derived hazard ratios (HRs) were synthesized using random-effects meta-analyses. MAIN OUTCOMES AND MEASURES: Incident coronary heart disease (myocardial infarction, coronary revascularization, and unstable angina), nonfatal myocardial infarction, and cardiovascular death (from cardiac or cerebrovascular causes). RESULTS: The meta-analysis included 7 cohort studies involving 21 401 individuals (mean [SD] age, 53.7 [10.2] years; 10 012 men [46.8%]). Mean (SD) follow-up was 15.3 (4.5) years (326 392 person-years at risk). In models adjusting for age, sex, and race/ethnicity, higher MCP-1 levels at baseline were associated with increased risk of coronary heart disease (HR per 1-SD increment in MCP-1 levels: 1.06 [95% CI, 1.01-1.11]; P = .01), nonfatal myocardial infarction (HR, 1.07 [95% CI, 1.01-1.13]; P = .02), and cardiovascular death (HR, 1.12 [95% CI, 1.05-1.20]; P &lt; .001). In analyses comparing MCP-1 quartiles, these associations followed dose-response patterns. After additionally adjusting for vascular risk factors, the risk estimates were attenuated, but the associations of MCP-1 levels with cardiovascular death remained statistically significant, as did the association of MCP-1 levels in the upper quartile with coronary heart disease. There was no significant heterogeneity; the results did not change in sensitivity analyses excluding events occurring in the first 5 years after MCP-1 measurement, and the risk estimates were stable after additional adjustments for circulating levels of interleukin-6 and high-sensitivity C-reactive protein. CONCLUSIONS AND RELEVANCE: Higher circulating MCP-1 levels are associated with higher long-term cardiovascular mortality in community-dwelling individuals free of overt cardiovascular disease. These findings provide further support for a key role of MCP-1-signaling in cardiovascular disease.

IMPORTANCE: Low-density lipoprotein cholesterol (LDL-C) is an important modifiable risk factor for atherosclerotic cardiovascular disease. It is unclear whether the percentage LDL-C lowering with pharmacotherapies differs on the basis of baseline LDL-C levels. OBJECTIVE: To evaluate the association between baseline LDL-C levels and the percentage LDL-C reduction with a statin, ezetimibe, and a PCSK9 inhibitor. DESIGN, SETTING, AND PARTICIPANTS: This secondary exploratory study analyzed data from 3 randomized placebo-controlled clinical trials (Aggrastat to Zocor–Thrombolysis in Myocardial Infarction 21 [A to Z–TIMI 21], Improved Reduction of Outcomes: Vytorin Efficacy International Trial [IMPROVE-IT], and Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]) of lipid-lowering therapies (statin, ezetimibe, and a PCSK9 inhibitor) and included participants with atherosclerotic cardiovascular disease. Analyses took place form April to October 2020. INTERVENTIONS: In A to Z–TIMI 21, 1:1 randomization to simvastatin, 40 mg, daily for 30 days followed by 80 mg daily thereafter vs placebo for 4 months followed by simvastatin, 20 mg, daily thereafter. In IMPROVE-IT, 1:1 randomization to ezetimibe, 10 mg, daily plus simvastatin, 40 mg, daily vs placebo plus simvastatin, 40 mg, daily. In FOURIER, 1:1 randomization to evolocumab, 140 mg, every 2 weeks or 420 mg monthly vs matching placebo. MAIN OUTCOMES AND MEASURES: The percentage LDL-C reduction at either 1 month (A to Z–TIMI 21, IMPROVE-IT) or 3 months (FOURIER) as a function of baseline LDL-C level. Data were modeled using a generalized linear regression model. RESULTS: A total of 3187 patients from A to Z–TIMI 21, 10 680 patients from IMPROVE-IT, and 25 847 patients from FOURIER were analyzed. There was a higher percentage reduction in LDL-C levels with evolocumab in patients with lower baseline LDL-C levels, ranging from 59.4% (95% CI, 59.1%-59.8%) in patients with a baseline LDL-C level of 130 mg/dL to 66.1% (95% CI, 65.6%-66.6%) in patients with a baseline LDL-C level of 70 mg/dL (P &lt; .001). In contrast, across the same range of baseline LDL-C level, there was a more modest difference for simvastatin (44.6% [95% CI, 43.9%-45.2%] vs 47.8% [95% CI, 46.4%-49.2%]; P &lt; .001) and minimal difference with ezetimibe (25.0% [95% CI, 23.3%-26.6%] vs 26.2% [95% CI, 24.2%-28.1%]; P = .007). CONCLUSIONS AND RELEVANCE: The percentage LDL-C reduction with statins, ezetimibe, and PCSK9 inhibition is not attenuated in patients starting with lower baseline LDL-C levels and is 6.6% greater for PCSK9 inhibition. These data are encouraging for the use of intensive LDL-C–lowering therapy even for patients with lower LDL-C levels.

IMPORTANCE: Self-identified Black race is associated with higher hypertension prevalence and worse blood pressure (BP) control compared with other race/ethnic groups. The contribution of genetic West African ancestry to these racial disparities appears not to have been completely determined. OBJECTIVE: To determine the association between the proportion of West African ancestry with the response to antihypertensive medication, BP control, kidney function, and risk of adverse cardiovascular (CV) events among self-identified Black individuals in the Systolic Blood Pressure Intervention Trial (SPRINT). DESIGN, SETTING, AND PARTICIPANTS: This post hoc analysis of the SPRINT trial incorporated data from a multicenter study of self-identified Black participants with available West African ancestry proportion, estimated using 106 biallelic autosomal ancestry informative genetic markers. Recruitment started on October 20, 2010, and ended on August 20, 2015. Data were analyzed from May 2020 to September 2020. MAIN OUTCOMES AND MEASURES: Trajectories of BP and kidney function parameters on follow-up of the trial were assessed across tertiles of the proportion of West African ancestry using linear mixed-effect modeling after adjustment for potential confounders. Multivariable adjusted Cox models evaluated the association of West African ancestry with the risk of composite CV events (nonfatal myocardial infarction, CV death, and heart failure event). RESULTS: Among 2466 participants in the current analysis (1122 women [45.5%]; median West African ancestry, 81% [interquartile range, 73%-87%]), there were 120 composite CV events (4.9%) over a mean (SD) of 3.2 (0.9) years of follow-up. At baseline, mean (SD) high-density lipoprotein cholesterol levels were higher (tertile 3: 56.5 [15.0] mg/dL vs tertile 1: 54.2 [14.9] mg/dL; P = .006), smoking prevalence (never smoking: tertile 3: 367 [47.9%] vs tertile 1: 372 [42.2%]; P = .009) and mean (SD) Framingham Risk scores (tertile 3: 16.7 [9.7] vs tertile 1: 18.1 [10.2]; P = .01) were lower, and baseline BP was not different across increasing tertiles of West African ancestry. On follow-up, there was no evidence of differences in longitudinal trajectories of BP, kidney function parameters, or left ventricular mass (Cornell voltage by electrocardiogram) across tertiles of West African ancestry in either intensive or standard treatment arms. In adjusted Cox models, higher West African ancestry was associated with a lower risk of a composite CV event after adjustment for potential confounders (adjusted hazard ratio per 5% higher West African ancestry, 0.92 [95% CI, 0.85-0.99]). CONCLUSIONS AND RELEVANCE: Among self-reported Black individuals enrolled in SPRINT, the trajectories of BP, kidney function, and left ventricular mass over time were not different across tertiles of the proportion of West African ancestry. A higher proportion of West African ancestry was associated with a modestly lower risk for CV events. These findings suggest that extrinsic and structural societal factors, more than genetic ancestry, may be the major drivers of the well-established racial disparity in cardiovascular health associated with hypertension.

This study evaluated the application of a biomarker-based risk score to identify individuals with dysglycemia who are at high risk for incident heart failure (HF) and to inform allocation of effective preventive interventions.

IMPORTANCE: Higher coronary artery calcium (CAC) identifies individuals at increased atherosclerotic cardiovascular disease (ASCVD) risk. Whether it can also identify individuals likely to derive net benefit from aspirin therapy is unclear. OBJECTIVE: To examine the association between CAC, bleeding, and ASCVD and explore the net estimated effect of aspirin at different CAC thresholds. DESIGN, SETTING, AND PARTICIPANTS: Prospective population-based cohort study of Dallas Heart Study participants, free from ASCVD and not taking aspirin at baseline. Data were analyzed between February 1, 2020, and July 15, 2020. EXPOSURES: Coronary artery calcium score in the following categories: 0, 1-99, and 100 or higher. MAIN OUTCOMES AND MEASURES: Major bleeding and ASCVD events were identified from International Statistical Classification of Diseases and Related Health Problems, Ninth Revision codes. Meta-analysis–derived aspirin effect estimates were applied to observed ASCVD and bleeding rates to model the net effect of aspirin at different CAC thresholds. RESULTS: A total of 2191 participants (mean [SD], age 44 [9.1] years, 1247 women [57%], and 1039 black individuals [47%]) had 116 major bleeding and 123 ASCVD events over a median follow-up of 12.2 years. Higher CAC categories (CAC 1-99 and ≥100 vs CAC 0) were associated with both ASCVD and bleeding events (hazard ratio [HR], 1.6; 95% CI, 1.1-2.4; HR, 2.6; 95% CI, 1.5-4.3; HR, 4.8; 95% CI, 2.8-8.2; P &lt; .001; HR, 5.3; 95% CI, 3.6-7.9; P &lt; .001), but the association between CAC and bleeding was attenuated after multivariable adjustment. Applying meta-analysis estimates, irrespective of CAC, aspirin use was estimated to result in net harm in individuals at low (&lt;5%) and intermediate (5%-20%) 10-year ASCVD risk and net benefit in those at high (≥20%) ASCVD risk. Among individuals at lower bleeding risk, a CAC score of at least 100 identified individuals who would experience net benefit, but only in those at borderline or higher (≥5%) 10-year ASCVD risk. In individuals at higher bleeding risk, there would be net harm from aspirin irrespective of CAC and ASCVD risk. CONCLUSIONS AND RELEVANCE: Higher CAC is associated with both ASCVD and bleeding events, with a stronger association with ASCVD. A high CAC score identifies individuals estimated to derive net benefit from primary prevention aspirin therapy from those who would not, but only in the setting of lower bleeding risk and estimated ASCVD risk that is not low.

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IMPORTANCE: The association of the Hospital Readmission Reduction Program (HRRP) with reductions in racial disparities in 30-day outcomes for myocardial infarction (MI), is unknown, including whether this varies by HRRP hospital penalty status. OBJECTIVE: To assess temporal trends in 30-day readmission and mortality rates among black and nonblack patients discharged after hospitalization for acute MI at low-performing and high-performing hospitals, as defined by readmission penalty status after HRRP implementation. DESIGN, SETTING, AND PARTICIPANTS: This observational cohort analysis used data from the multicenter National Cardiovascular Data Registry Chest Pain–MI Registry centers that were subject to the first cycle of HRRP, between January 1, 2008, and November 30, 2016. All patients hospitalized with MI who were included in National Cardiovascular Data Registry Chest Pain–MI Registry were included in the analysis. Data were analyzed from April 2018 to September 2019. EXPOSURES: Hospital performance category and race (black compared with nonblack patients). Centers were classified as high performing or low performing based on the excess readmission ratio (predicted to expected 30-day risk adjusted readmission rate) for MI during the first HRRP cycle (in October 2012). MAIN OUTCOMES AND MEASURES: Thirty-day all-cause readmission and mortality rates. RESULTS: Among 753 hospitals that treated 155 397 patients with acute MI (of whom 11 280 [7.3%] were black), 399 hospitals (53.0%) were high performing. Thirty-day readmission rates declined over time in both black and nonblack patients (annualized 30-day readmission rate: 17.9% vs 20.8%). Black (compared with nonblack) race was associated with higher unadjusted odds of 30-day readmission in both low-performing and high-performing centers (odds ratios: before HRRP: low-performing hospitals, 1.14 [95% CI, 1.03-1.26]; P = .01; high-performing hospitals, 1.17 [95% CI, 1.04-1.32]; P = .01; after HRRP: low-performing hospitals, 1.23 [95% CI, 1.13-1.34]; P &lt; .001; high-performing hospitals, 1.25 [95% CI, 1.12-1.39]; P &lt; .001). However, these racial differences were not significant after adjustment for patient characteristics. The 30-day mortality rates declined significantly over time in nonblack patients, with stable (nonsignificant) temporal trends among black patients. Adjusted associations between race and 30-day mortality showed that 30-day mortality rates were significantly lower among black (compared with nonblack) patients in the low-performing hospitals (odds ratios: pre-HRRP, 0.79 [95% CI, 0.63-0.97]; P = .03; post-HRRP, 0.80 [95% CI, 0.68-0.95]; P = .01) but not in high-performing hospitals. Finally, the association between race and 30-day outcomes did not vary after the HRRP period began in either high-performing or low-performing hospitals. CONCLUSIONS AND RELEVANCE: In this analysis, 30-day readmission rates among patients with MI declined over time for both black and nonblack patients. Differences in race-specific 30-day readmission rates persisted but appeared to be attributable to patient-level factors. The 30-day mortality rates have declined for nonblack patients and remained stable among black patients. Implementation of the HRRP was not associated with improvement or worsening of racial disparities in readmission and mortality rates.

Thirty-day risk standardized readmission and mortality rates (RSRR, RSMR) are key determinants for hospital performance for cardiovascular conditions such as acute myocardial infarction (AMI) and heart failure (HF). We evaluated whether individual hospitals in the USA perform similarly for HF and AMI over time based on readmission and mortality metrics.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment.

Supplemental Digital Content is available in the text.Although coronary thrombus overlying a disrupted atherosclerotic plaque has long been considered the hallmark and the primary therapeutic target for acute myocardial infarction (MI), multiple other mechanisms are now known to cause or contribute to MI. It is further recognized that an MI is just one of many types of acute myocardial injury. The Fourth Universal Definition of Myocardial Infarction provides a taxonomy for acute myocardial injury, including 5 subtypes of MI and nonischemic myocardial injury. The diagnosis of MI is reserved for patients with myocardial ischemia as the cause of myocardial injury, whether attributable to acute atherothrombosis (type 1 MI) or supply/demand mismatch without acute atherothrombosis (type 2 MI). Myocardial injury in the absence of ischemia is categorized as acute or chronic nonischemic myocardial injury. However, optimal evaluation and treatment strategies for these etiologically distinct diagnoses have yet to be defined. Herein, we review the epidemiology, risk factor associations, and diagnostic tools that may assist in differentiating between nonischemic myocardial injury, type 1 MI, and type 2 MI. We identify limitations, review new research, and propose a framework for the diagnostic and therapeutic approach for patients who have suspected MI or other causes of myocardial injury.

The study sought to determine whether processes of care and long-term clinical outcomes for heart failure (HF) admissions across Get With The Guidelines-Heart Failure (GWTG-HF) program participating centers differ according to HF-specific risk-adjusted 30-day readmission rates (excess readmission ratio [ERR]) as determined by the Hospital Readmission Reduction Program (HRRP).

Galectin-3 is a biomarker associated with inflammation and fibrosis in cardiac, liver, and renal disease. Galectin-3 is higher in overweight and obese individuals; whether an association with diabetes exists independent of weight is unknown.

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Statin therapy has been shown to reduce major vascular events and vascular mortality in a wide range of individuals, but there is uncertainty about its efficacy and safety among older people. We undertook a meta-analysis of data from all large statin trials to compare the effects of statin therapy at different ages.

IMPORTANCE: African Americans have a higher burden of heart failure (HF) risk factors and clinical HF than other racial/ethnic groups. However, the factors underlying the transition from at-risk to clinical HF in African Americans are not well understood. OBJECTIVE: To evaluate the contributions of left ventricular hypertrophy (LVH) and subclinical myocardial injury as determined by abnormal high-sensitivity cardiac troponin-I (hs-cTnI) measurements toward HF risk among African Americans. DESIGN, SETTING, AND PARTICIPANTS: This prospective, community-based cohort study was conducted between July 2016 and September 2018 and included African American participants from Jackson, Mississippi enrolled in the Jackson Heart Study without prevalent HF who had hs-cTnI measurements and an echocardiographic examination at baseline. Participants were stratified into categories based on the presence or absence of LVH and subclinical myocardial injury (category 1: hs-cTnI &lt;4 ng/L in women and &lt;6 ng/L in men; category 2: 4-10 ng/L in women and 6-12 ng/L in men; category 3: >10 ng/L in women and >12 ng/L in men). MAIN OUTCOMES AND MEASURES: Adjusted associations between LVH, subclinical myocardial injury, and the risk of incident HF hospitalization were assessed using Cox proportional hazards models. RESULTS: The study included 3987 participants (2552 women [64%]; 240 (6.0%) with LVH; 1003 (25.1%) with myocardial injury) with 285 incident HF events over a median follow-up of 9.8 years (interquartile range, 8.9-10.6 years). In adjusted analyses, higher LV mass and subclinical myocardial injury were independently associated with the risk of HF with a significant interaction between the 2 (Pint &lt; 0.001). The highest risk of HF was noted among individuals with both LVH and myocardial injury (absolute incidence, 35%; adjusted hazard ratio [aHR; vs no LVH and no myocardial injury], 5.35; 95% CI, 3.66-7.83). A significant interaction by sex was also observed. Men with LVH and subclinical myocardial injury had an almost 15-fold higher risk of HF (aHR, 14.62; 95% CI, 7.61-28.10) vs those with neither LVH nor injuries. By contrast, women with this phenotype had a nearly 4-fold higher risk of HF (aHR, 3.81; 95% CI, 2.40-6.85). CONCLUSIONS AND RELEVANCE: The combination of LVH and subclinical myocardial injury identifies a malignant, preclinical HF phenotype in African Americans with a very high risk of HF, particularly among men. This finding could have implications for future screening strategies that are designed to prevent HF in the population.

Supplemental Digital Content is available in the text.

Supplemental Digital Content is available in the text.

IMPORTANCE: Health insurance is effective in preventing financial hardship from unexpected major health care events. However, it is also essential to assess whether vulnerable patients, particularly those from low-income families, are adequately protected from longitudinal health care costs for common chronic conditions such as atherosclerotic cardiovascular disease (ASCVD). OBJECTIVE: To examine the annual burden of total out-of-pocket health expenses among low-income families that included a member with ASCVD. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study of the Medical Expenditure Panel Survey from January 2006 through December 2015, all families with 1 or more members with ASCVD were identified. Families were classified as low income if they had an income under 200% of the federal poverty limit. Analyses began December 2017. MAIN OUTCOMES AND MEASURES: Total annual inflation-adjusted out-of-pocket expenses, inclusive of insurance premiums, for all patients with ASCVD. We compared these expenses against annual family incomes. Out-of-pocket expenses of more than 20% and more than 40% of family income defined high and catastrophic financial burden, respectively. RESULTS: We identified 22 521 adults with ASCVD, represented in 20 600 families in the Medical Expenditure Panel Survey. They correspond to an annual estimated 23 million or 9.9% of US adults with a mean (SE) age of 65 (0.2) years and included 10.9 million women (47.1%). They were represented in 21 million or 15% of US families. Of these, 8.2 million families (39%) were low income. The mean annual family income was $57 143 (95% CI, $55 377-$58 909), and the mean out-of-pocket expense was $4415 (95% CI, $3735-$3976). While financial burden from health expenses decreased throughout the study, even in 2014 and 2015, low-income families had 3-fold higher odds than mid/high–income families of high financial burden (21.4% vs 7.6%; OR, 3.31; 95% CI, 2.55-4.31) and 9-fold higher odds of catastrophic financial burden (9.8% vs 1.2%; OR, 9.35; 95% CI, 5.39-16.20), representing nearly 2 million low-income families nationally. Further, even among the insured, 1.6 million low-income families (21.8%) experienced high financial burden and 721 000 low-income families (9.8%) experienced catastrophic out-of-pocket health care expenses in 2014 and 2015. CONCLUSIONS AND RELEVANCE: One in 4 low-income families with a member with ASCVD, including those with insurance coverage, experience a high financial burden, and 1 in 10 experience a catastrophic financial burden due to cumulative out-of-pocket health care expenses. To alleviate economic disparities, policy interventions must extend focus to improving not only access, but also quality of coverage, particularly for low-income families.

IMPORTANCE: Among patients hospitalized with heart failure (HF), the long-term clinical implications of hospitalization at hospitals based on 30-day risk-standardized mortality rates (RSMRs) is not known. OBJECTIVE: To evaluate the association of hospital-specific 30-day RSMR with long-term survival among patients hospitalized with HF in the American Heart Association Get With The Guidelines–HF registry. DESIGN, SETTING, AND PARTICIPANTS: The longitudinal observational study included 106 304 patients with HF who were admitted to 317 centers participating in the Get With The Guidelines–HF registry from January 1, 2005, to December 31, 2013, and had Medicare-linked follow-up data. Hospital-specific 30-day RSMR was calculated using a hierarchical logistic regression model. In the model, 30-day mortality rate was a binary outcome, patient baseline characteristics were included as covariates, and the hospitals were treated as random effects. The association of 30-day RSMR-based hospital groups (low to high 30-day RSMR: quartile 1 [Q1] to Q4) with long-term (1-year, 3-year, and 5-year) mortality was assessed using adjusted Cox models. Data analysis took place from June 29, 2017, to February 19, 2018. EXPOSURES: Thirty-day RSMR for participating hospitals. MAIN OUTCOMES AND MEASURES: One-year, 3-year, and 5-year mortality rates. RESULTS: Of the 106 304 patients included in the analysis, 57 552 (54.1%) were women and 84 595 (79.6%) were white, and the median (interquartile range) age was 81 (74-87) years. The 30-day RSMR ranged from 8.6% (Q1) to 10.7% (Q4). Hospitals in the low 30-day RSMR group had greater availability of advanced HF therapies, cardiac surgery, and percutaneous coronary interventions. In the primary landmarked analyses among 30-day survivors, there was a graded inverse association between 30-day RSMR and long-term mortality (Q1 vs Q4: 5-year mortality, 73.7% vs 76.8%). In adjusted analysis, patients admitted to hospitals in the high 30-day RSMR group had 14% (95% CI, 10-18) higher relative hazards of 5-year mortality compared with those admitted to hospitals in the low 30-day RSMR group. Similar findings were observed in analyses of survival from admission, with 22% (95% CI, 18-26) higher relative hazards of 5-year mortality for patients admitted to Q4 vs Q1 hospitals. CONCLUSIONS AND RELEVANCE: Lower hospital-level 30-day RSMR is associated with greater 1-year, 3-year, and 5-year survival for patients with HF. These differences in 30-day survival continued to accrue beyond 30 days and persisted long term, suggesting that 30-day RSMR may be a useful HF performance metric to incentivize quality care and improve long-term outcomes.

To examine the association of acute kidney injury (AKI) with long-term outcomes after myocardial infarction (MI), and evaluate whether effect modification is present according to baseline chronic kidney disease (CKD) status.

IMPORTANCE: Identifying high-performing surgical valve centers with the best surgical outcomes is challenging. Hospital surgical volume is a frequently used surrogate for outcomes. However, its ability to distinguish low-performing and high-performing hospitals remains unknown. OBJECTIVE: To examine the association of hospital procedure volume with hospital performance for aortic and mitral valve (MV) surgical procedures. DESIGN, SETTING, AND PARTICIPANTS: Within an all-payer nationally representative data set of inpatient hospitalizations, this study identified 682 unique hospitals performing surgical aortic valve replacement (SAVR) and MV replacement and repair with or without coronary artery bypass grafting (CABG) between 2007 and 2011. Procedural outcomes were further assessed for a 10-year period (2005-2014) to assess representativeness of study period. MAIN OUTCOMES AND MEASURES: In-hospital risk-standardized mortality rate (RSMR) calculated using hierarchical models and an empirical bayesian approach with volume-based shrinkage that allowed for reliability adjustment. RESULTS: At 682 US hospitals, 70 295 SAVR, 19 913 MV replacement, and 17 037 MV repair procedures were performed between 2007 and 2011, with a median annual volume of 43 (interquartile range [IQR], 23-76) SAVR, 13 (IQR, 6-22) MV replacement, and 9 (IQR, 4-19) MV repair procedures. Of 225 SAVR hospitals in the highest-volume tertile, 34.7% and 36.0% were in the highest-RSMR tertile for SAVR + CABG and isolated SAVR procedures, respectively, while 21.5% and 17.5% of the 228 SAVR hospitals in the lowest-volume tertile were in the lowest respective RSMR tertile. Similarly, 36.8% and 43.5% of hospitals in the highest tertile of volume for MV replacement and repair, respectively, were in the corresponding highest-RSMR tertile, and 17.4% and 11.2% of the low-volume hospitals were in the lowest-RSMR tertile for MV replacement and repair, respectively. There was limited correlation between outcomes for SAVR and MV procedures at an institution. If solely volume-based tertiles were used to categorize hospitals for quality, 44.7% of all valve hospitals would be misclassified (as either low performing or high performing) when assessing performance based on tertiles of RSMR. CONCLUSIONS AND RELEVANCE: Hospital procedure volume alone frequently misclassifies hospital performance with regard to risk-standardized outcomes after aortic and MV surgical procedures. Valve surgery quality improvement endeavors should focus on a more comprehensive assessment that includes risk-adjusted outcomes rather than hospital volume alone.

While early and sustained patency of the infarct related artery is necessary following ST elevation myocardial infarction, tissue and microvascular perfusion must also be restored. Effective tools for assessing microvascular [...]