Peripheral artery disease, chronic kidney disease, and recurrent admissions for acute decompensated heart failure: The ARIC study.

BACKGROUND AND AIMS: Peripheral artery disease (PAD) has not only been associated with recurrent hospitalization for acute decompensated heart failure (ADHF) but is also associated with chronic kidney disease (CKD), a known risk factor for worse heart failure outcomes. The interaction of CKD with PAD in post-discharge ADHF outcomes is not well known. METHODS: Since 2005, hospitalizations for ADHF were sampled from 4 US regions by the Atherosclerosis Risk in Communities (ARIC) study and classified by physician review. We examined the adjusted association of PAD with 1-year ADHF readmissions, in patients with and without CKD (defined by glomerular filtration rate [GFR] ≤60 mL/min/1.73 m2 [stage 3a or worse]). RESULTS: From 2005 to 2018, there were 1049 index hospitalizations for patients with ADHF (mean age 77 years, 66 % white) with creatinine data, who were discharged alive. Of these, 155 (15 %) had PAD and 66 % had CKD. In comparison to those without PAD, patients with PAD had more comorbid conditions and higher 1-year ADHF readmission rates, irrespective of CKD status. After adjustment, PAD was associated with a greater risk of 1-year ADHF readmissions, both for patients with concomitant CKD (HR, 1.70; 95 % CI: 1.29-2.24) and those without CKD (HR, 1.97; 95 % CI: 1.14-3.40); p-interaction = 0.8. CONCLUSION: Among patients hospitalized with ADHF, those with concurrent PAD have more prevalent cardiovascular comorbidities and higher likelihood of 1-year ADHF readmission, irrespective of CKD status. Integrating a more holistic approach in management of patients with concomitant heart failure, PAD and CKD may be an important strategy to improve the prognosis in this vulnerable population.

Epidemiological profile and clinical outcomes of very young (<35 years) and young (35-50 years) patients with STEMI: Insights from the NORIN STEMI registry.

BACKGROUND: Despite significant progress in primary prevention, rates of myocardial infarction (MI) in South Asian population is alarmingly high. OBJECTIVES: We sought to compare risk factor profiles and outcomes between individuals with ST-Segment Elevation Myocardial Infarction (STEMI) in young (<50 years) and old (≥50 years) age groups. METHODS: North India STEMI Registry (NORIN-STEMI) is a prospective observational registry of patients hospitalised with STEMI. We conducted a study of young patients (<50 years) regarding their risk factors for coronary artery disease (CAD), in-hospital and 30-day mortality and compared with their older counterpart. RESULTS: Among 5335 patients enrolled, 1752 (32.8%) were young and were 19 years younger than the older cohort. Major risk factors in young patients were physical inactivity (75.1%) and alcohol intake (67.8%). Higher prevalence of tobacco use (66.6% vs 52.4%), but lower prevalence of diabetes (16% vs 26.3%) and hypertension (18.5% vs 29.9%) were seen in young STEMI. Young patients were less likely to die both in-hospital (5.9% vs 10.0%) and at 30-days (11.1% vs 16.2%). Left ventricular ejection fraction (LVEF) < 30% at admission [OR: 8.00, 95% confidence interval (CI): 4.60-13.90, P < 0.001 in-hospital, OR: 3.92, 95% CI: 2.69-5.73 at 30-days] and female sex were strongest predictors of mortality. CONCLUSIONS: Young STEMI patients constituted one-third of total cohort. Most of them were tobacco consumers with lesser prevalence of diabetes and hypertension. They were less likely to die both in-hospital and at 30 days because of earlier presentation to a health care facility and hence a relatively preserved LVEF.

Combined polygenic scores for ischemic stroke risk factors aid risk assessment of ischemic stroke.

BACKGROUND: Current risk assessment for ischemic stroke (IS) is limited to clinical variables. We hypothesize that polygenic scores (PGS) of IS (PGSIS) and IS-associated diseases such as atrial fibrillation (AF), venous thromboembolism (VTE), coronary artery disease (CAD), hypertension (HTN), and Type 2 diabetes (T2D) may improve the performance of IS risk assessment. METHODS: Incident IS was followed for 479,476 participants in the UK Biobank who did not have an IS diagnosis prior to the recruitment. Lifestyle variables (obesity, smoking and alcohol) at the time of study recruitment, clinical diagnoses of IS-associated diseases, PGSIS, and five PGSs for IS-associated diseases were tested using the Cox proportional-hazards model. Predictive performance was assessed using the C-statistic and net reclassification index (NRI). RESULTS: During a median average 12.5-year follow-up, 8374 subjects were diagnosed with IS. Known clinical variables (age, gender, clinical diagnoses of IS-associated diseases, obesity, and smoking) and PGSIS were all independently associated with IS (P < 0.001). In addition, PGSIS and each PGS for IS-associated diseases was also independently associated with IS (P < 0.001). Compared to the clinical model, a joint clinical/PGS model improved the C-statistic for predicting IS from 0.71 to 0.73 (P < 0.001) and significantly reclassified IS risk (NRI = 0.017, P < 0.001), and 6.48% of subjects were upgraded from low to high risk. CONCLUSIONS: Adding PGSs of IS and IS-associated diseases to known clinical risk factors statistically improved risk assessment for IS, demonstrating the supplementary value of inherited susceptibility measurement . However, its clinical utility is likely limited due to modest improvements in predictive values.

Early versus delayed coronary angiography in patients with out-of-hospital cardiac arrest and no ST-segment elevation: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Recent randomized controlled trials did not show benefit of early/immediate coronary angiography (CAG) over a delayed/selective strategy in patients with out-of-hospital cardiac arrest (OHCA) and no ST-segment elevation. However, whether selected subgroups, specifically those with a high pretest probability of coronary artery disease may benefit from early CAG remains unclear. METHODS: We included all randomized controlled trials that compared a strategy of early/immediate versus delayed/selective CAG in OHCA patients and no ST elevation and had a follow-up of at least 30 days. The primary outcome of interest was all-cause death. Odds ratios (OR) were calculated and pooled across trials. Interaction testing was used to assess for heterogeneity of treatment effects. RESULTS: In total, 1512 patients (67 years, 26% female, 23% prior myocardial infarction) were included from 5 randomized controlled trials. Early/immediate versus delayed/selective CAG was not associated with a statistically significant difference in odds of death (OR 1.12, 95%-CI 0.91-1.38), with similar findings for the composite outcome of all-cause death or neurological deficit (OR 1.10, 95%-CI 0.89-1.36). There was no effect modification for death by age, presence of a shockable initial cardiac rhythm, history of coronary artery disease, presence of an ischemic event as the presumed cause of arrest, or time to return of spontaneous circulation (all P-interaction > 0.10). However, early/immediate CAG tended to be associated with higher odds of death in women (OR 1.52, 95%-CI 1.00-2.31, P = 0.050) than in men (OR 1.04, 95%-CI 0.82-1.33, P = 0.74; P-interaction 0.097). CONCLUSION: In OHCA patients without ST-segment elevation, a strategy of early/immediate versus delayed/selective CAG did not reduce all-cause mortality across major subgroups. However, women tended to have higher odds of death with early CAG.

Temporal trends and outcomes of patients with chronic limb-threatening ischemia with and without history of coronary artery disease: insights from the us national inpatient sample database.

BACKGROUND: The burden and prognostic significance of coronary artery disease (CAD) in adults with peripheral artery disease and chronic limb-threatening ischemia (CLTI) is unknown. METHODS: Temporal trends in prevalence of significant CAD (history of myocardial infarction or coronary revascularizations) in hospitalizations for CLTI were determined using the 2000 to 2018 National Inpatient Sample (NIS) database. A multivariable regression analysis of outcomes was performed based on presence or absence of CAD. RESULTS: Among 13 575 099 hospitalizations for CLTI (41% female, 69% white, mean age 69 years), 23% had concomitant CAD, of which 11% underwent lower extremity arterial revascularization (43.6% endovascular and 56.4% surgical). The prevalence of concomitant CAD with CLTI increased from 15.3% in 2000 to 23.1% in 2018. Furthermore, the frequency of endovascular revascularization in adults with CAD and CLTI increased from 15.1% to 48.3%, while there was a decreasing trend of surgical revascularization, from 84.9% to 51.7%. After multivariate adjustments, CLTI with CAD was associated with increased risk of in-hospital mortality (OR, 1.40; 95% CI, 1.32-1.47; P less than .0001) and bleeding requiring transfusion (OR, 1.10; 95% CI, 1.06-1.12; P less than .0001) compared with patients with CLTI without CAD. As compared with surgical revascularization, endovascular revascularization was associated with lower risk of in-hospital mortality in both patients with CLTI with CAD (OR, 0.69; 95% CI, 0.63-0.76; P less than .001) and CLTI without CAD (OR, 0.71; 95% CI, 0.67-0.76; P less than .001). CONCLUSIONS: Prevalence of CAD has increased in adults presenting with CLTI and is associated with poor outcomes, warranting the need for effective interventions and secondary prevention in this high-risk population.

Utility of Polygenic Scores for Differentiating Diabetes Diagnosis Among Patients With Atypical Phenotypes of Diabetes.

CONTEXT: Misclassification of diabetes type occurs in people with atypical presentations of type 1 diabetes (T1D) or type 2 diabetes (T2D). Although current clinical guidelines suggest clinical variables and treatment response as ways to help differentiate diabetes type, they remain insufficient for people with atypical presentations. OBJECTIVE: This work aimed to assess the clinical utility of 2 polygenic scores (PGSs) in differentiating between T1D and T2D. METHODS: Patients diagnosed with diabetes in the UK Biobank were studied (N = 41 787), including 464 (1%) and 15 923 (38%) who met the criteria for classic T1D and T2D, respectively, and 25 400 (61%) atypical diabetes. The validity of 2 published PGSs for T1D (PGST1D) and T2D (PGST2D) in differentiating classic T1D or T2D was assessed using C statistic. The utility of genetic probability for T1D based on PGSs (GenProb-T1D) was evaluated in atypical diabetes patients. RESULTS: The joint performance of PGST1D and PGST2D for differentiating classic T1D or T2D was outstanding (C statistic = 0.91), significantly higher than that of PGST1D alone (0.88) and PGST2D alone (0.70), both P less than .001. Using an optimal cutoff of GenProb-T1D, 23% of patients with atypical diabetes had a higher probability of T1D and its validity was independently supported by clinical presentations that are characteristic of T1D. CONCLUSION: PGST1D and PGST2D can be used to discriminate classic T1D and T2D and have potential clinical utility for differentiating these 2 types of diseases among patients with atypical diabetes.

Clinical Profiles, Outcomes, and Sex Differences of Patients With STEMI: Findings From the NORIN-STEMI Registry.

Background: Low- and middle-income countries account for most of the global burden of coronary artery disease. There is a paucity of data regarding epidemiology and outcomes for ST-segment elevation myocardial infarction (STEMI) patients in these regions. Objectives: The authors studied the contemporary characteristics, practice patterns, outcomes, and sex differences in patients with STEMI in India. Methods: NORIN-STEMI (North India ST-Segment Elevation Myocardial Infarction Registry) is an investigator-initiated prospective cohort study of patients presenting with STEMI at tertiary medical centers in North India. Results: Of 3,635 participants, 16% were female patients, one-third were <50 years of age, 53% had a history of smoking, 29% hypertension, and 24% diabetes. The median time from symptom onset to coronary angiography was 71 hours; the majority (93%) presented first to a non-percutaneous coronary intervention (PCI)-capable facility. Almost all received aspirin, statin, P2Y12 inhibitors, and heparin on presentation; 66% were treated with PCI (98% femoral access) and 13% received fibrinolytics. The left ventricular ejection fraction was <40% in 46% of patients. The 30-day and 1-year mortality rates were 9% and 11%, respectively. Compared with male patients, female patients were less likely to receive PCI (62% vs 73%; P < 0.0001) and had a more than 2-fold greater 1-year mortality (22% vs 9%; adjusted HR: 2.1; 95% CI: 1.7-2.7; P < 0.001). Conclusions: In this contemporary registry of patients with STEMI in India, female patients were less likely to receive PCI after STEMI and had a higher 1-year mortality compared with male patients. These findings have important public health implications, and further efforts are required to reduce these gaps.

Mortality in Patients Hospitalized With Acute Myocardial Infarction Without Standard Modifiable Risk Factors: The ARIC Study Community Surveillance.

Background Prevention strategies targeting standard modifiable cardiovascular risk factors (SMuRFs; diabetes, hypertension, smoking, hypercholesterolemia) are critical to improving cardiovascular disease outcomes. However, acute myocardial infarction (AMI) among individuals who lack 1 or more SMuRFs is not uncommon. Moreover, the clinical characteristics and prognosis of SMuRFless individuals are not well characterized. Methods and Results We analyzed AMI hospitalizations from 2000 to 2014 captured by the ARIC (Atherosclerosis Risk in Community) study community surveillance. AMI was classified by physician review using a validated algorithm. Clinical data, medications, and procedures were abstracted from the medical record. Main study outcomes included short- and long-term mortality within 28 days and 1 year of AMI hospitalization. Between 2000 and 2014, a total of 742 (3.6%) of 20 569 patients with AMI were identified with no documented SMuRFs. Patients without SMuRFs were less likely to receive aspirin, nonaspirin antiplatelet therapy, or beta blockers and less often underwent angiography and revascularization. Compared with those with one or more SMuRFs, patients without SMuRFs had significantly higher 28-day (odds ratio, 3.23 [95% CI, 1.78-5.88]) and 1-year (hazard ratio, 2.09 [95% CI, 1.29-3.37]) adjusted mortality. When examined across 5-year intervals from 2000 to 2014, the incidence of 28-day mortality significantly increased for patients without SMuRFs (7% to 15% to 27%), whereas it declined for those with 1 or more SMuRFs (7% to 5% to 5%). Conclusions Individuals without SMuRFs presenting with AMI have an increased risk of all-cause mortality with an overall lower prescription rate for guideline-directed medical therapy. These findings highlight the need for evidence-based pharmacotherapy during hospitalization and the need to discover new markers and mechanisms for early risk identification in this population.

Demographic and Regional Trends of Cardiovascular Diseases and Diabetes Mellitus-Related Mortality in the United States From 1999 to 2019.

OBJECTIVE: The purpose of this research was to study the contemporary trends in cardiovascular disease (CVD) and diabetes mellitus (DM)-related mortality. METHODS: We used the Centers for Disease Control and Prevention Wide-Ranging OnLine Data for Epidemiologic Research (CDC WONDER) database to identify adults ≥25 years old where both CVD and DM were listed as an underlying or contributing cause of death between 1999 and 2019. Crude and age-adjusted mortality rates per 100,000 population were determined. RESULTS: The overall age-adjusted mortality rate was 99.18 in 1999 and 91.43 in 2019, with a recent increase from 2014-2019 (annual percent change 1.0; 95% confidence interval [CI], 0.3-1.6). Age-adjusted mortality rate was higher for males compared with females, with increasing mortality in males between 2014 and 2019 (annual percent change 1.5; 95% CI, 0.9-2.0). Age-adjusted mortality rate was highest for non-Hispanic Black adults and was ∼2-fold higher compared with non-Hispanic White adults. Young and middle-aged adults (25-69 years) had increasing age-adjusted mortality rates in recent years. There were significant urban-rural disparities, and age-adjusted mortality rates in rural counties increased from 2014 to 2019 (annual percent change 2.2; 95% CI, 1.5-2.9); states in the 90th percentile of mortality had age-adjusted mortality rates that were ∼2-fold higher than those in the bottom 10th percentile of mortality. CONCLUSION: After an initial decrease in DM + CVD-related mortality for a decade, this trend has reversed, with increasing mortality from 2014 to 2019. Significant geographic and demographic disparities persist, requiring targeted health policy interventions to prevent the loss of years of progress.

Impact of Diabetes on Outcomes in Patients Hospitalized With Acute Myocardial Infarction: Insights From the Atherosclerosis Risk in Communities Study Community Surveillance.

Background Diabetes is associated with increased risk of acute myocardial infarction (AMI). The demographic trends, clinical presentation, management, and outcomes of patients with diabetes who are hospitalized with AMI have not been recently reported. Methods and Results The ARIC (Atherosclerosis Risk in Communities) study conducted hospital surveillance of AMI in 4 US communities. AMI was classified by physician review using a validated algorithm. Medications and procedures were abstracted from the medical record. From 2000 to 2014, 21 094 weighted hospitalizations for AMI were sampled. The prevalence of diabetes steadily increased, from 35% to 41% to 43% (P-trend<0.0001) across 2000 to 2004, 2005 to 2009, and 2010 to 2014, respectively. Patients with diabetes were older (61 versus 59 years of age), more often Black (44% versus 31%), and more commonly women (42% versus 34%). The burden of cardiovascular comorbidities was higher with diabetes and increased temporally. Patients with diabetes less often presented with ST-segment elevation (9% versus 17%) or acute chest pain (72% versus 80%), and had higher mean GRACE (Global Registry of Acute Coronary Syndrome) score (123 versus 109), Thrombolysis in Myocardial Ischemia (TIMI) score (4.3 versus 4.0), and Killip class (1.9 versus 1.5). Patients with diabetes had a lower adjusted probability of receiving aspirin (relative probability, 0.95 [95% CI, 0.91-0.99]), nonaspirin antiplatelets (0.93 [95% CI, 0.86-0.99]), coronary angiography (0.85 [95% CI, 0.78-0.92]), and coronary revascularization (0.85 [95% CI, 0.76-0.92]). Diabetes was associated with a 52% higher hazard of all-cause 1-year mortality (hazard ratio, 1.52 [95% CI, 1.23-1.89]). Conclusions Diabetes is associated with higher risk of death in patients hospitalized with AMI, highlighting the need for adherence to evidence-based therapies in this high-risk population.

ANGPTL3 inhibition, dyslipidemia, and cardiovascular diseases.

Optimal management of low-density lipoprotein cholesterol (LDL-C) is a central tenet in the primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD). However, significant residual cardiovascular risk remains despite achieving guideline-directed LDL-C levels, in part due to mixed hyperlipidemia with elevated fasting and non-fasting triglyceride-rich lipoprotein levels. Advances in human genetics have identified angiopoietin-like 3 (ANGPTL3) as a promising therapeutic target to lower cardiovascular risk. Evidence accrued from genetic epidemiological studies demonstrate that ANGPTL3 loss of function is strongly associated with lowering of circulating LDL-C, triglyceride-rich lipoproteins and concurrent risk reduction in development of coronary artery disease. Pharmacological inhibition of ANGPTL3 with monoclonal antibodies, antisense oligonucleotides and gene editing are in development with early studies showing their safety and efficacy in lowering in both, LDL-C and TGs, circumventing a key limitation of previous therapies. Monoclonal antibodies targeting ANGPTL3 are approved for clinical use in homozygous familial hypercholesteremia in USA and Europe. Although promising, future studies focusing on long-term beneficial effect in reducing cardiovascular events with inhibition of ANGPTL3 are warranted.

Epidemiology and Outcomes of Aortic Stenosis in Acute Decompensated Heart Failure: The ARIC Study.

BACKGROUND: Few studies characterize the epidemiology and outcomes of aortic stenosis (AS) in acute decompensated heart failure (ADHF). This study investigates the significance of AS in contemporary patients who have experienced an ADHF hospitalization. METHODS: The ARIC study (Atherosclerosis Risk in Communities) surveilled ADHF hospitalizations for residents ≥55 years of age in 4 US communities. ADHF cases were stratified by left ventricular ejection fraction (LVEF). Demographic differences in AS burden and the association of varying AS severities with mortality were estimated using multivariable logistic regression. RESULTS: From 2005 through 2014, there were 3597 (weighted n=16 692) ADHF hospitalizations of which 48.6% had an LVEF <50% and 51.4% an LVEF ≥50%. AS prevalence was 12.1% and 18.7% in those with an LVEF <50% and ≥50%, respectively. AS was less likely in Black than White patients regardless of LVEF: LVEF <50% (odds ratio [OR], 0.34 [95% CI, 0.28-0.42]); LVEF ≥50% (OR, 0.51 [95% CI, 0.44-0.59]). Higher AS severity was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.16 [95% CI, 1.04-1.28]); LVEF ≥50% (OR, 1.40 [95% CI, 1.28-1.54]). Sensitivity analyses excluding severe AS patients detected that mild/moderate AS was independently associated with 1-year mortality in both LVEF subgroups: LVEF <50% (OR, 1.23 [95% CI, 1.02-1.47]); LVEF ≥50% (OR, 1.31 [95% CI, 1.14-1.51]). CONCLUSIONS: Among patients who have experienced an ADHF hospitalization, AS is prevalent and portends poor mortality outcomes. Notably, mild/moderate AS is independently associated with 1-year mortality in this high-risk population.

Revascularizations and limb outcomes of hospitalized patients with diabetic peripheral arterial disease in the contemporary era.

BACKGROUND: Concomitant diabetes mellitus and peripheral artery disease (PAD) is a complex disease process. This retrospective analysis of the National Inpatient Sample sought to understand trends in limb outcomes of this unique and prevalent cohort of patients. METHODS: The National Inpatient Sample was queried between 2003 and 2017 for hospitalizations of patients with both type 2 diabetes mellitus and PAD. Trends in hospitalizations, limb outcomes, vascular interventions, and costs were analyzed. RESULTS: There were 10,303,673 hospitalizations of patients with concomitant diabetes mellitus and PAD that were identified between 2003 and 2017. The prevalence of hospitalizations associated with this disease process increased from 1644 to 3228 per 100,000 hospitalizations, a 96.4% increase. This included an increase of 288 to 587 per 100,000 hospitalizations of patients aged 18 to 49 years old, which was accompanied by a 10.8% increase in minor amputations. Nontraumatic lower extremity amputations decreased overall. Black and Hispanic ethnicity were associated with an increased risk for amputation, along with Medicaid insurance and lower income quartile. Inpatient endovascular revascularization has increased over time with an associated decrease in open revascularization procedures. Amputation-related hospital costs significantly increased from $6.6 billion in 2003 to $14.8 billion in 2017. CONCLUSIONS: An alarming increase of disease prevalence, negative in-hospital limb outcomes, and costs are seen in the current era in this analysis of patients with concurrent diabetes and PAD.

Trends in Veno-Arterial Extracorporeal Life Support With and Without an Impella or Intra-Aortic Balloon Pump for Cardiogenic Shock.

Background Mechanical circulatory support devices, such as the intra-aortic balloon pump (IABP) and Impella, are often used in patients on veno-arterial extracorporeal life support (VA-ECLS) with cardiogenic shock despite limited supporting clinical trial data. Methods and Results Hospitalizations for cardiogenic shock from 2016 to 2018 were identified from the National Inpatient Sample. Trends in the use of VA-ECLS with and without an IABP or Impella were assessed semiannually. Multivariable logistic regression and general linear regression evaluated the association of Impella and IABP use with in-hospital outcomes. Overall, 12 035 hospitalizations with cardiogenic shock and VA-ECLS were identified, of which 3115 (26%) also received an IABP and 1880 (16%) an Impella. Use of an Impella with VA-ECLS substantially increased from 10% to 18% over this period (P<0.001), whereas an IABP modestly increased from 25% to 26% (P<0.001). In-hospital mortality decreased 54% to 48% for VA-ECLS only, 61% to 58% for VA-ECLS with an Impella, and 54% to 49% for VA-ECLS with an IABP (P<0.001 each). Most (57%) IABPs or Impellas were placed on the same day as VA-ECLS. After adjustment, there were no differences in in-hospital mortality or length of stay with the addition of an IABP or Impella compared with VA-ECLS alone. Conclusions From 2016 to 2018 in the United States, use of an Impella and IABP with VA-ECLS significantly increased. More than half of Impellas and IABPs were placed on the same day as VA-ECLS, and the use of a second mechanical circulatory support device did not impact in-hospital mortality. Further studies are needed to decipher the optimal timing and patient selection for this growing practice.

Association of Serial High-Sensitivity Cardiac Troponin T With Subsequent Cardiovascular Events in Patients Stabilized After Acute Coronary Syndrome: A Secondary Analysis From IMPROVE-IT.

Importance: Studies have demonstrated an association between single measures of high-sensitivity troponin (hsTn) and future cardiovascular events in patients with chronic coronary syndromes. However, limited data exist regarding the association between changes in serial values of hsTn and subsequent cardiovascular events in this patient population. Objective: To evaluate the association between changes in high-sensitivity troponin T (hsTnT) and subsequent cardiovascular events in patients stabilized after acute coronary syndrome (ACS). Design, Setting, and Participants: This is a secondary analysis from the Improved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT), a randomized clinical trial of ezetimibe vs placebo on a background of simvastatin in 18 144 patients hospitalized for an ACS across 1147 sites in 39 countries. The current biomarker substudy includes the 6035 participants consenting to the biomarker substudy with available hsTnT at months 1 and 4. Data were collected from October 26, 2005, through July 8, 2010, with the database locked October 21, 2014. Data were analyzed from February 28, 2021, through August 14, 2022. Main Outcomes and Measures: The outcomes of interest were cardiovascular death, myocardial infarction (MI), stroke, or hospitalization for heart failure (HHF). Associations of absolute and relative changes in hsTnT between month 1 and month 4 as a function of the starting month 1 hsTnT and the composite outcome were examined using landmark analyses. Results: Of 6035 patients in this analysis (median [IQR] age, 64 [57-71]), 1486 (24.6%) were female; 361 (6.0%) were Asian; 121 were (2.0%) Black; 252 (4.2%) were Spanish descent; 4959 were (82.2%) White; and 342 (5.7%) reported another race (consolidated owing to small numbers), declined to respond, or were not asked to report race owing to regulatory prohibitions. Most patients (4114 [68.2%]) had stable hsTnT values (change <3 ng/L), with 1158 (19.2%) and 763 (12.6%) having changes of 3 to less than 7 ng/L and 7 ng/L or more, respectively. After adjustment for clinical risk factors and stratification by the starting month 1 hsTnT level, an absolute increase in hsTnT of 7 ng/L or more was associated with a more than 3-fold greater risk of the composite outcome (adjusted hazard ratio [aHR], 3.33; 95% CI, 1.99-5.57; P < .001), whereas decreases of 7 ng/L or more were associated with similar to lower risk (aHR, 0.51; 95% CI, 0.26-1.03; P = .06) compared with stable values. There was a stepwise association moving from larger absolute decreases (aHR, 0.51; 95% CI, 0.26-1.03) to larger absolute increases (aHR, 3.33; 95% CI, 1.99-5.57) in hsTnT with future risk of the composite outcome (P trend <.001). A similar association was observed when analyzed on the basis of relative percent and continuous change. Conclusions and Relevance: Among stable patients post-ACS, changes in hsTnT were associated with a gradient of risk of subsequent cardiovascular events across the range of starting hsTnT values. Serial assessment of hsTnT may refine risk stratification with the potential to guide therapy decisions in this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT00202878.

Missed Opportunities for Screening and Management of Dysglycemia among Patients Presenting with Acute Myocardial Infarction in North India: The Prospective NORIN STEMI Registry.

Background: Dysglycemia is a major and increasingly prevalent cardiometabolic risk factor worldwide, but is often undiagnosed even in high-risk patients. We evaluated the impact of protocolized screening for dysglycemia on the prevalence of prediabetes and diabetes among patients presenting with ST-segment elevation myocardial infarction (STEMI) in North India. Methods: We conducted a prospective NORIN STEMI registry-based study of patients presenting with STEMI to two government-funded tertiary care medical centers in New Delhi, India, from January to November 2019. Hemoglobin A1c (HbA1c) was collected at presentation as part of the study protocol, irrespective of baseline glycemic status. Results: Among 3,523 participants (median age 55 years), 855 (24%) had known diabetes. In this group, baseline treatment with statins, sodium-glucose cotransporter 2 inhibitors, or glucagon-like peptide-1 receptor agonists was observed in 14%, <1%, and 1% of patients, respectively. For patients without known diabetes, protocolized inpatient screening identified 737 (28%) to have prediabetes (HbA1c 5.7-6.4%) and 339 (13%) to have newly detected diabetes (HbA1c ≥ 6.5%). Patients with prediabetes (49%), newly detected diabetes (53%), and established diabetes (48%) experienced higher rates of post-MI LV dysfunction as compared to euglycemic patients (42%). In-hospital mortality (5.6% for prediabetes, 5.1% for newly detected diabetes, 10.3% for established diabetes, 4.3% for euglycemia) and 30-day mortality (8.1%, 7.6%, 14.4%, 6.6%) were higher in patients with dysglycemia. Compared with euglycemia, prediabetes (adjusted odds ratio (aOR) 1.44 [1.12-1.85]), newly detected diabetes (aOR 1.57 [1.13-2.18]), and established diabetes (aOR 1.51 [1.19-1.94]) were independently associated with higher odds of composite 30-day all-cause mortality or readmission. Conclusions: Among patients presenting with STEMI in North India, protocolized HbA1c screening doubled the proportion of patients with known dysglycemia. Dysglycemia was associated with worse clinical outcomes at 30 days, and use of established pharmacotherapeutic risk-reduction strategies among patients with known diabetes was rare, highlighting missed opportunities for screening and management of dysglycemia among high-risk patients in North India.

P2Y12 inhibitor versus aspirin monotherapy for secondary prevention of cardiovascular events: meta-analysis of randomized trials.

Aim: To compare the efficacy and safety of P2Y12 inhibitor or aspirin monotherapy for secondary prevention in patients with atherosclerotic cardiovascular disease (ASCVD). Methods and results: Medline, Embase, and Cochrane Central databases were searched to identify randomized trials comparing monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention in patients with ASCVD (cardiovascular, cerebrovascular, or peripheral artery disease). The primary outcome was major adverse cardiac events (MACE). Secondary outcomes were myocardial infarction (MI), stroke, all-cause mortality, and major bleeding. A random-effects model was used to calculate risk ratios (RR) and the corresponding 95% confidence interval (CI) and heterogeneity among studies was assessed using the Higgins I2 value. A total of 9 eligible trials (5 with clopidogrel and 4 with ticagrelor) with 61 623 patients were included in our analyses. Monotherapy with P2Y12 inhibitors significantly reduced the risk of MACE by 11% (0.89, 95% CI 0.84-0.95, I2 = 0%) and MI by 19% (0.81, 95% CI 0.71-0.92, I2 = 0%) compared with aspirin monotherapy. There was no significant difference in the risk of stroke (0.85, 95% CI 0.73-1.01), or all-cause mortality (1.01, 95% CI 0.92-1.11). There was also no significant difference in the risk of major bleeding with P2Y12 inhibitor monotherapy compared with aspirin (0.94, 95% CI 0.72-1.22, I2 = 42.6%). Results were consistent irrespective of the P2Y12 inhibitor used. Conclusion: P2Y12 inhibitor monotherapy for secondary prevention is associated with a significant reduction in atherothrombotic events compared with aspirin alone without an increased risk of major bleeding.

Meta-Analysis Comparing Venoarterial Extracorporeal Membrane Oxygenation With or Without Impella in Patients With Cardiogenic Shock.

Cardiogenic shock is associated with high short-term mortality. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is increasingly used as a mechanical circulatory support strategy for patients with refractory cardiogenic shock. A drawback of this hemodynamic support strategy is increased left ventricular (LV) afterload, which is mitigated by concomitant use of Impella (extracorporeal membrane oxygenation with Impella [ECPELLA]). However, data regarding the benefits of this approach are limited. We conducted a systematic search of Medline, EMBASE, and Cochrane databases to identify studies including patients with cardiogenic shock reporting clinical outcomes with Impella plus VA-ECMO compared with VA-ECMO alone. Primary outcome was short-term all-cause mortality (in-hospital or 30-day mortality). Secondary outcomes included major bleeding, hemolysis, continuous renal replacement therapy, weaning from mechanical circulatory support, limb ischemia, and transition to destination therapy with LV assist device (LVAD) or cardiac transplant. Of 2,790 citations, 7 observational studies were included. Of 1,054 patients with cardiogenic shock, 391 were supported with ECPELLA (37%). Compared with patients on only VA-ECMO support, patients with ECPELLA had a lower risk of short-term mortality (risk ratio [RR] 0.89 [0.80 to 0.99], I2 = 0%, p = 0.04) and were significantly more likely to receive a heart transplant/LVAD (RR 2.03 [1.44 to 2.87], I2 = 0%, p <0.01). However, patients with ECPELLA had a higher risk of hemolysis (RR 2.03 [1.60 to 2.57], I2 = 0%, p <0.001), renal failure requiring continuous renal replacement therapy (RR 1.46 [1.23 to 174], I2 = 11%, p <0.0001), and limb ischemia (RR 1.67 [1.15 to 2.43], I2 = 0%, p = 0.01). In conclusion, among patients with cardiogenic shock requiring VA-ECMO support, concurrent LV unloading with Impella had a lower likelihood of short-term mortality and a higher likelihood of progression to durable LVAD or heart transplant. However, patients supported with ECPELLA had higher rates of hemolysis, limb ischemia, and renal failure requiring continuous renal replacement therapy. Future prospective randomized are needed to define the optimal treatment strategy in this high-risk cohort.