Incident Cardiovascular Outcomes Research Articles

Dietary Minerals and Incident Cardiovascular Outcomes among Never-Smokers in a Danish Case-Cohort Study.

Background: Diet is known to impact cardiovascular disease (CVD) risk, but evidence for the essential minerals of magnesium (Mg), calcium (Ca), and potassium (K) is inconsistent. Methods: We conducted a case-cohort study within a non-smoking subgroup of the Danish Diet, Cancer and Health cohort, a prospective study of 50-64-year-olds recruited between 1993-1997. We identified incident heart failure (HF), acute myocardial infarction (AMI) and stroke cases through 2015 with an 1135-member subcohort. We measured the dietary intake of minerals, also known as elements, and calculated a combined dietary intake (CDI) score based on joint Ca, Mg and K intakes (mg/d) from Food Frequency Questionnaires. We estimated adjusted hazard ratios (HRs) with Cox proportional hazard models. Results: Most HRs examining associations between CDI score and CVD were null. However, the third quartile of CDI was associated with a lower risk for heart failure (HR: 0.89; 95% CI: 0.67, 1.17), AMI (HR: 0.79; 95% CI: 0.60, 1.04), and stroke (HR: 0.63; 95% CI: 0.44, 0.88). Conclusions: We did not find consistent evidence to suggest that higher levels of essential minerals are associated with incident HF, AMI, and stroke, though results suggest a potential U-shaped relationship between select minerals and CVD outcomes.

The association of TNF inhibitor use with incident cardiovascular events in radiographic axial spondyloarthritis

BackgroundWhether tumor necrosis factor inhibitor (TNFi) use is cardioprotective among individuals with radiographic axial spondyloarthritis (r-axSpA), who have heightened cardiovascular (CV) risk, is unclear. We tested the association of TNFi use with incident CV outcomes in r-axSpA. MethodsWe identified a r-axSpA cohort within a Veterans Affairs database between 2002 and 2019 using novel phenotyping methods and secondarily using ICD codes. TNFi use was assessed as a time-varying exposure using pharmacy dispense records. The primary outcome was incident CV disease identified using ICD codes for coronary artery disease, myocardial infarction or stroke. We fit Cox models with inverse probability weights to estimate the risk of each outcome with TNFi use versus non-use. Analyses were performed in the overall cohort, and separately in two periods (2002–2010, 2011–2019) to account for secular trends. ResultsUsing phenotyping we identified 26,928 individuals with an r-axSpA diagnosis (mean age 63.4 years, 94 % male); at baseline 3633 were TNFi users and 23,295 were non-users. During follow-up of a mean 3.3 ± 4.2 years, 674 (18.6 %) TNFi users had incident CVD versus 11,838 (50.8 %) non-users. In adjusted analyses, TNFi use versus non-use was associated with lower risk of incident CVD (HR 0.34, 95 % CI 0.29–0.40) in the cohort overall, and in the two time periods separately. ConclusionIn this r-axSpA cohort identified using phenotyping methods, TNFi use versus non-use had a lower risk of incident CVD. These findings provide reassurance regarding the CV safety of TNFi agents for r-axSpA treatment. Replication of these results in other cohorts is needed.

Burden of atrial fibrillation risk and outcomes amongst patients attending cardiology and elderly medicine services: prospective in-hospital implementation of the FIND-AF algorithm

Abstract Background Screening for silent AF is becoming increasingly important (1, 2), and the FIND-AF algorithms can use routinely-collected data to identify individuals at higher risk for undiagnosed AF (3). There may be a much higher prevalence of patients at risk for AF and its complications in a hospital environment compared with the community (4). Purpose We prospectively implemented the FIND-AF algorithm within cardiology and geriatric services to quantify the burden of AF risk amongst all-comers, and to understand their outcomes over the next 6 months. Methods We prospectively implemented the FIND-AF algorithm in the cardiology and geriatric departments of three UK hospitals for consecutive inpatient or outpatient attendances from February 1 to July 13th 2023. We assessed the number of individuals attending each service eligible for an AF screening protocol (exclusion criteria: age <30 years, history of AF, on a palliative care pathway, use of oral anticoagulation), and calculated the burden of AF risk in each service. Patients were followed up for 6 months for the primary outcome of incident AF, heart failure (HF), stroke/transient ischaemic attack (TIA)/systemic embolism, and death. Incident diagnoses were the first record of that condition in primary or secondary care records. Rate ratios (RRs) with 95% confidence intervals (CIs) for combined incident cardiovascular outcomes or death were derived through Poisson regression for predicted higher versus lower AF risk. Results Of 467 consecutive patients, 364 were eligible for AF screening. 66 were excluded due to a previous diagnosis of AF, 25 were already prescribed a long-term oral anticoagulant, 5 were on a palliative care pathway and 7 were aged <30 years. Baseline characteristics of each cohort are summarised in Table 1. Of patients eligible for AF screening, those attending geriatrics were at higher risk of incident AF than patients attending cardiology (median FIND-AF score: geriatrics, 0.015, 95% CI 0.008 - 0.024; cardiology, 0.005, 95% CI 0.001-0.015; p<0.05; distributions of risk summarised in Figure 1) and had a higher stroke risk. Absolute risk of AF was greater than 5% within the next 6 months for 11.6% and 9.1% of geriatric and cardiology patients, respectively. Of the eligible cohort, 328 had follow up at 6 months, with 46 experiencing the primary outcome (9, 7, 3, and 27 recorded cases of AF, HF, stroke/TIA, and death, respectively). The higher predicted risk cohort, compared to lower predicted risk, had a higher risk of combined incident AF, heart failure, or stroke/TIA/systemic embolism (Rate ratio: 5.59, 95% CI 1.13-101.01) and death (RR 9.68, 2.06-172.85). Conclusions The FIND-AF algorithm can be prospectively implemented in hospital records to identify cardiology and geriatric patients at risk of incident AF, heart failure, thromboembolic disease and death. There is an opportunity to conduct risk-guided screening in the context of hospital attendances.

Metabolic Obesity Phenotypes and Incident Cardiovascular Outcomes in Middle-Aged and Older Korean Adults: A Longitudinal 10-Year Analysis of the Korean Genome and Epidemiology Study.

Background: This study investigated the association of four metabolic obesity phenotypes with incident coronary artery disease and stroke in a large-scale, community population-based, prospective Korean cohort observed for over 10 years. Methods: The study participants included 7374 adults aged 40-69 years, drawn from the Korean Genome and Epidemiology Study. Participants with different metabolic obesity phenotypes were categorized according to body weight and metabolic health status into four groups: metabolically healthy nonobese (MHNO), metabolically healthy obese (MHO), metabolically unhealthy nonobese (MUHNO), and metabolically unhealthy obese (MUHO). Combined cardiovascular events were defined as coronary artery disease and stroke. We used multivariate Cox proportional hazards regression models to prospectively assess hazard ratios (HRs) with 95% confidence intervals (CIs) for incident coronary artery disease or stroke over 10 years after the baseline survey. Results: During the follow-up period, newly developed coronary artery disease, stroke, and combined cardiovascular events were diagnosed in 151 (2.0%), 137 (1.9%), and 283 (3.8%) participants, respectively. After adjusting for confounding variables, the HRs (95% CIs) for incident combined cardiovascular events were 1.81 (1.34-2.46) in the MUHO group, 1.29 (0.92-1.81) in the MUHNO group, and 1.21 (0.81-1.79) in the MHO group compared with those in the MHNO group. Conclusions: This study revealed distinct risks associated with four metabolic obesity phenotypes concerning incident coronary artery disease and stroke. After adjusting for potential confounding variables, the results indicated that MUHO, but not MUHNO or MHO, showed a higher risk of developing coronary artery disease and stroke than MHNO.

Abstract P210: Incident Venous Thromboembolism and Subsequent Risk of Cardiovascular Outcomes: The Atherosclerosis Risk in Communities (ARIC) Study

Background: Venous thromboembolism (VTE) and atherothrombosis have different mechanisms of thrombosis formation. A few previous studies reported those having a VTE have greater risk of incident atherothrombotic disease. These studies have several limitations, such as inadequate adjustment for key confounders (e.g., obesity), selected study populations in clinical trials, and small sample size. Moreover, the links of VTE to heart failure (HF) and peripheral artery disease (PAD) are not well understood. Hypothesis: VTE is independently associated with a range of incident cardiovascular outcomes. Methods: In 12,988 ARIC participants without history of VTE or cardiovascular disease at baseline (1987-89), we quantified the association of VTE, as a time-varying exposure, with incident myocardial infarction (MI), stroke, HF, PAD (overall and its severe form, critical limb ischemia [CLI]) using multivariable Cox regression. We also considered unprovoked and provoked VTE separately. Results: Over a median follow-up of 25 years, 901 participants experienced incident VTE. In the same timeframe, there were 1,950 MI events, 1,247 stroke events, 2,981 HF events, and 516 PAD cases (including 207 CLI cases). Participants with VTE, compared to those without, had a higher risk of all cardiovascular outcomes ( Table ). The associations were particularly evident for incident PAD and CLI (adjusted HR 2.32 [95% CI 1.53, 3.52] and 3.44 [2.01, 5.88], respectively). Provoked VTE showed similar associations with all cardiovascular outcomes, whereas unprovoked VTE was significantly associated with MI, HF, and CLI only ( Table ). Conclusions: In this large community-based study, VTE was robustly associated with subsequent risk of different cardiovascular outcomes, independent of potential confounders. Patients with VTE should be considered at high risk of other cardiovascular outcomes and receive optimal preventive therapy for cardiovascular diseases, including atherosclerotic disease and HF.

MicroRNAs are associated with cardiac biomarkers, cardiac structure and function and incident outcomes in heart failure.

The association between microRNAs (miRNAs) and established cardiac biomarkers is largely unknown. We aimed to measure the association between plasma miRNAs and N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac troponin I, soluble urokinase-type plasminogen activator receptor (suPAR), and galectin-3 with cardiac structure and function and clinical outcomes. We quantified 32 plasma miRNAs using the FirePlex miRNA assay and measured biomarkers in 139 individuals with symptomatic heart failure (HF). We used principal component (PC) analysis and linear regression to evaluate the association between miRNAs and biomarkers with ventricular size and function by echocardiography and Cox modelling for the incidence of a first composite event of HF hospitalization, heart transplant, left ventricular assist device implant, or death. The mean (standard deviation) age at baseline was 64.3 (12.4) years, 33 (24%) were female, and 122 (88%) were White. A total of 45 events occurred over a median follow-up of 368 (interquartile range 234, 494) days. Baseline NT-proBNP (β=-2.0; P=0.001) and miRNA PC2 (β=2.6; P=0.002) were associated with baseline left ventricular ejection fraction. NT-proBNP (β=20.6; P=0.0004), suPAR (β=-39.6; P=0.005), and PC4 (β=21.1; P=0.02) were associated with baseline left ventricular end-diastolic volumes. NT-proBNP [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.28-2.18, P=0.0002], galectin-3 (HR 2.02, 95% CI 1.05-3.91, P=0.036), PC3 (HR 1.75, 95% CI 1.23-2.49, P=0.002), and PC4 (HR 1.67, 95% CI 1.1-2.52, P=0.016) were independently associated with incident events. Biomarkers and miRNA PCs are associated with cardiac structure and function and incident cardiovascular outcomes. Combining information from miRNAs provides prognostic information beyond biomarkers in HF.

Myocardial Aging among a Population-Based Cohort Is Associated with Adverse Cardiovascular Outcomes and Sex-Specific Differences among Older Adults

Introduction: Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. Methods: Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. Results: A total of 956 participants (mean age 63 ± 12.9 years, n = 424 males [44%]) were categorized based on mitral peak early-to-late diastolic filling velocity (E/A) ratios: E/A <0.8 (28%), E/A 0.8–1.2 (39%), E/A (29%), E/A >2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI: 2.24–3.56) and 0.45 per 100 person-years (95% CI: 0.26–0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes was significantly different among E/A categories (log-rank p = 0.0269). E/A <0.8 (HR 1.80, 95% CI: 1.031, 3.14, p = 0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI: 2.62–4.84) and 0.75 per 100 person-years (95% CI: 0.39–1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI: 1.56–3.16) and 0.21 per 100 person-years (95% CI: 0.067–0.64) for all-cause death. For E/A <0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8–1.2 category (HR 2.49, 95% CI: 1.18, 5.23, p = 0.017). Conclusion: Myocardial aging was an independent predictor of cardiovascular outcomes in community-dwelling older adults prior to clinical CVD. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.

MOVEMENT AND HEALTH: NOVEL INSIGHTS INTO PHYSICAL ACTIVITY, ENERGY EXPENDITURE, AND MOTOR FUNCTION

Abstract Physical activity, energy expenditure, and motor function are well-established predictors of health and longevity with aging. Traditionally, most research using these measures has focused on speed of movement and intensity of activity. More recently, interest has grown in ways to refine these movement-related measures—and the methods used to analyze them—to improve predictive and discriminatory power for older adult health outcomes. This symposium will focus on measures derived from traditional in-lab assessments of motor function as well as free-living accelerometry, and their novel application across a variety of large U.S. cohort studies. Ms. Marino will present analyses on the links among heart rate variability, physical activity, and cognitive health in the Atherosclerosis Risk in Communities (ARIC) study. Dr. Dougherty will present the association of fine and gross motor function with MRI-derived brain volumes in the Baltimore Longitudinal Study of Aging (BLSA). Dr. Davoudi will present evidence on the link between physical activity quantities and variability with dementia in the National Health and Aging Trends Study (NHATS). Dr. Schumacher will compare measures of absolute and relative physical activity intensity with incident cardiovascular outcomes and all-cause mortality in the Objective Physical Activity and Cardiovascular Health (OPACH) Study. Finally, Dr. Wanigatunga will describe objectively measured physical activity quantities and patterns by self-reported fatigue levels and HIV status in the Multicenter AIDS Cohort Study (MACS). Collectively, these presentations will highlight novel ways to utilize motor function, energy expenditure, and physical activity data to advance prevention science and promote healthy aging. \ This is an Epidemiology of Aging Interest Group Sponsored Symposium.

Cardiovascular and renal outcomes with varying degrees of kidney disease in high-risk people with type 2 diabetes: An epidemiological analysis of data from the AMPLITUDE-O trial.

To estimate the incidence of a major adverse cardiovascular event (MACE) and a composite kidney outcome across estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (UACR) levels, and to determine whether efpeglenatide's effect varies with these indices. AMPLITUDE-O trial data were used to estimate the relationship of eGFR, UACR, and Kidney Disease Improving Global Outcomes (KDIGO) category to the hazard of MACE and the kidney composite. Interactions on these outcomes between eGFR and the UACR, and between each of these variables and efpeglenatide were also assessed. Baseline eGFR and UACR were available for 3983 participants (mean age 64.5 years). During a median follow-up of 1.8 years, the hazards of MACE and the kidney composite for the lowest versus highest eGFR third were 1.6 (95% confidence interval [CI] 1.2, 2.2) and 2.3 (95% CI 1.9, 2.8), respectively. The hazards for the highest versus the lowest UACR third were 2.3 (95% CI 1.8, 3.1) and 18.0 (95% CI 12.7, 25.5), respectively, and for the high- versus low-risk KDIGO categories the hazards were 2.4 (95% CI 1.8, 3.1) and 16.0 (95% CI 11.6, 22.0), respectively. eGFR and UACR were independent determinants of both outcomes, but negatively interacted with each other for the kidney outcome. Efpeglenatide's effect on both outcomes did not vary with any kidney disease measure (all interaction p values ≥0.26). In high-risk people with diabetes, eGFR, UACR, and KDIGO category have different relationships to incident cardiovascular and kidney outcomes. The beneficial effect of efpeglenatide on these outcomes is independent of kidney-related risk category.

Cardiac dysfunction in survivors of sepsis: a scoping review

BackgroundSepsis is associated with an increased risk of adverse cardiovascular events in a magnitude comparable to other major cardiovascular risk factors. Sepsis is one of the most common reasons for...

Once-weekly glucagon-like peptide-1 receptor agonists vs dipeptidyl peptidase-4 inhibitors: cardiovascular effects in people with diabetes and cardiovascular disease

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1 RAs), which have proven cardiovascular benefits, are recommended in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). However, there is limited real-world evidence comparing the effects of once-weekly (OW) GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP-4is). This observational cohort study (1/1/2017–9/30/2021) used data from the Optum Clinformatics® Data Mart to compare time to incident clinical cardiovascular outcomes, health care resource utilization (HCRU), and medical costs in new adult users of OW GLP-1 RAs and DPP-4is with T2D and ASCVD.MethodsTime to occurrence of ischemic stroke, myocardial infarction (MI), or their composite and ASCVD-related and all-cause HCRU and medical costs were investigated. Baseline characteristics were balanced using inverse probability of treatment weighting. Survival analyses were conducted to compare risks during exposure.ResultsOW GLP-1 RA users (weighted N = 25,287) had 26%, 22%, and 24% lower risk of ischemic stroke, MI, and their composite, respectively, compared with DPP-4i users (weighted N = 39,684; all P < 0.01). Compared with DPP-4i users, OW GLP-1 RA users had 25% and 26% lower ASCVD-related and all-cause hospitalization costs, 19% and 23% lower ASCVD-related and all-cause medical costs, 23% and 27% fewer ASCVD-related and all-cause hospitalizations, 13% and 8% fewer ASCVD-related and all-cause outpatient visits, and 8% fewer all-cause ER visits (all P < 0.01).ConclusionsIn adults with T2D and ASCVD, OW GLP-1 RAs are associated with reduced stroke and MI risks and ASCVD-related and all-cause HCRU and costs vs DPP-4is.

Adverse cardiovascular outcomes and sex-specific differences among older adults with cardiac ageing

Abstract Background Despite growing calls to tackle aging-related cardiovascular disease (CVD), the role of detecting early diastolic dysfunction such as those observed in aging, prior to clinical disease, is of unclear clinical benefit. Methods Myocardial function determined by echocardiography was examined in association with incident cardiovascular outcomes or all-cause death by Cox proportional hazards model. Sex-based differences in outcomes were included. Results 956 participants [mean age 63±12.9 years, n=424 males (44%)] were categorized based on mitral peak early to late diastolic filling velocity (E/A) ratios: E/A &amp;lt;0.8 (28%), E/A 0.8-1.2 (39%), E/A (29%), E/A &amp;gt;2.0 (4%). Incidence rate (IR) for non-fatal cardiovascular outcomes was 2.83 per 100 person-years (95% CI 2.24-3.56), and 0.45 per 100 person-years (95% CI 0.26-0.80) for all-cause death. Event-free survival from non-fatal cardiovascular outcomes were significantly different among E/A categories (log-rank p=0.0269). E/A&amp;lt;0.8 (HR 1.80, 95%CI 1.031, 3.14, p=0.039) was associated with non-fatal cardiovascular outcomes. Among men, IR for cardiovascular outcomes was 3.56 per 100 person-years (95% CI 2.62-4.84), and 0.75 per 100 person-years (95% CI 0.39-1.44) for all-cause death. Among women, IR for cardiovascular outcomes was 2.22 per 100 person-years (95% CI 1.56-3.16), and 0.21 per 100 person-years (95% CI 0.067-0.64) for all-cause death. For E/A&amp;lt;0.8 category, women had significantly higher risks of non-fatal cardiovascular outcomes, compared to E/A 0.8-1.2 category (HR 2.49, 95%CI 1.18, 5.23, p=0.017). Conclusion Myocardial ageing was an independent predictor of cardiovascular outcomes. Impaired myocardial relaxation was prevalent in both sexes but associated with worse outcomes in women, suggestive of sex differences in age-related biology.Myocardial Ageing in the Community

Atherosclerotic Cardiovascular Disease Risk and Longitudinal Risk Factor Management Among Patients With Breast Cancer

BackgroundCardiovascular disease is the leading cause of noncancer mortality for breast cancer survivors. Data are limited regarding patient-level atherosclerotic cardiovascular disease (ASCVD) risk estimation and preventive medication use. This study aimed to characterize ASCVD risk and longitudinal preventive medication use for a cohort of patients with nonmetastatic breast cancer. Patients and MethodsThis retrospective cohort study included 326 patients at an academic medical center in Boston, Massachusetts diagnosed with nonmetastatic breast cancer or ductal carcinoma in situ from January 2009 through December 2015. Patient demographics, clinical characteristics, laboratory studies, medication exposure, and incident cardiovascular outcomes were collected. Estimated 10-year ASCVD risk was calculated for all patients from nonlaboratory clinical parameters. ResultsMedian follow up time was 6.5 years (IQR 5.0, 8.1). At cancer diagnosis, 23 patients (7.1%) had established ASCVD. Among those without ASCVD, 10-year estimated ASCVD risk was ≥20% for 77 patients (25.4%) and 7.5% to <20% for 114 patients (37.6%). Two-hundred and sixteen patients (66.3%) had an indication for lipid-lowering therapy at cancer diagnosis, 123 of whom (57.0%) received a statin during the study. Among 100 patients with ASCVD or estimated 10-year ASCVD risk ≥20%, 92 (92.0%) received an antihypertensive medication during the study. Clinic blood pressure >140/90 mmHg was observed in 33.0% to 55.6% of these patients at each follow up assessment. ConclusionA majority of patients in this breast cancer cohort had an elevated risk of ASCVD at the time of cancer diagnosis. Modifiable ASCVD risk factors were frequently untreated or uncontrolled in the years following cancer treatment.

Cardiovascular outcomes between COVID-19 and non-COVID-19 pneumonia: a nationwide cohort study

BackgroundPrevious studies that assessed the risk of cardiovascular outcomes in survivors of coronavirus disease 2019 (COVID-19) were likely limited by lack of generalizability and selection of controls nonrepresentative of a counterfactual situation regarding COVID-19-related hospitalization. This study determined whether COVID-19 hospitalization was associated with incident cardiovascular outcomes compared to non-COVID-19 pneumonia hospitalization.MethodsNationwide population-based study conducted using the Korean National Health Insurance Service database. A cohort of 132,784 inpatients with COVID-19 (October 8, 2020–September 30, 2021) and a cohort of 31,173 inpatients with non-COVID-19 pneumonia (January 1–December 31, 2019) were included. The primary outcome was the major adverse cardiovascular event (MACE; a composite of myocardial infarction and stroke). Hazard ratios (HRs) with 95% confidence intervals (CIs) of all outcomes of interest were estimated between inverse probability of treatment-weighted patients with COVID-19 and non-COVID-19 pneumonia.ResultsAfter weighting, the COVID-19 and non-COVID-19 pneumonia groups included 125,810 (mean [SD] age, 47.2 [17.6] years; men, 49.3%) and 28,492 patients (mean [SD] age, 48.6 [18.4] years; men, 47.2%), respectively. COVID-19 hospitalization was not associated with an increased risk of the MACE (HR, 0.84; 95% CI 0.69–1.03). However, the MACE (HR, 7.30; 95% CI 3.29–16.21), dysrhythmia (HR, 1.88; 95% CI 1.04–3.42), acute myocarditis (HR, 11.33; 95% CI 2.97–43.20), myocardial infarction (HR, 6.78; 95% CI 3.03–15.15), congestive heart failure (HR, 1.95; 95% CI 1.37–2.77), and thrombotic disease (HR, 8.26; 95% CI 4.06–16.83) risks were significantly higher in patients with COVID-19 aged 18–39 years. The findings were consistent after adjustment for preexisting cardiovascular disease. COVID-19 hospitalization conferred a higher risk of acute myocarditis (HR, 6.47; 95% CI 2.53–16.52) or deep vein thrombosis (HR, 1.97; 95% CI 1.38–2.80), regardless of vaccination status.ConclusionsHospitalized patients with COVID-19 were not at an increased risk of cardiovascular outcomes compared to patients with non-COVID-19 pneumonia. Further studies are needed to evaluate whether the increased risk of cardiovascular outcomes is confined to younger patients.

NT-proBNP and cardiovascular event risk in individuals with prediabetes undergoing cardiovascular evaluation

AimsCardiovascular risk assessment beyond traditional risk factors in subjects with prediabetes is not well-established. Here, we evaluated the utility of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in predicting incident adverse cardiovascular outcomes in prediabetic subjects. MethodsNT-proBNP was analyzed in 3,235 stable subjects with prediabetes undergoing cardiovascular risk evaluation and followed for both 3-year major adverse cardiac events (MACE; death, myocardial infarction, stroke), and 5-year all-cause mortality. ResultsUsing Cox proportional hazard models, we found that plasma NT-proBNP was associated with incident (3–year) MACE risk (Q4 vs Q1, HR 6.04 [95%CI 4.17–8.76], P < 0.001) and 5-year mortality risk (HR 8.64 [95%CI 5.78–12.9], P < 0.001). These associations remained significant after adjustments for traditional cardiovascular risk factors, multiple indices of glycemic control, cardiovascular disease (CVD), left ventricular ejection fraction (LVEF), and medication (e.g. diuretic) use (adjusted HR for 3-year MACE 2.65 [95% CI 1.16–6.05], P < 0.05; and adjusted HR for 5-year mortality 3.45 [95% CI 1.42–8.39], P < 0.01). NT-proBNP significantly improved the clinical prognostic value (C-statistic, NRI, IDI) for both 3-year MACE and 5-year death when added to models. ConclusionsNT-proBNP independently predicts increased long-term MACE and mortality risks in prediabetic subjects, and may help identify those for whom more aggressive global preventive efforts are indicated.

Acute Cardiovascular Events After COVID-19 in England in 2020: A Self-Controlled Case Series Study.

To assess the risk of incident cardiovascular outcomes after COVID-19 by level of cardiovascular risk in waves one and two of the pandemic in England in 2020. We conducted a self-controlled case-series study among adults aged 40-84 years with no pre-existing cardiovascular disease using linked data from the Clinical Practice Research Datalink. We generated season-adjusted incidence ratios (IRs) for first acute cardiovascular event after SARS-CoV-2 infection compared with baseline time before and >91 days after infection. We used composite and individual acute cardiovascular event outcomes including myocardial infarction, major ventricular arrhythmia, left ventricular heart failure, and ischemic stroke. We stratified by cardiovascular risk, using diagnosed hypertension and QRISK3 predicted risk, and by wave one and two of the pandemic. We included 1762 individuals, 76.6% had a QRISK3 score ≥10% and 59.4% had hypertension. The risk of any cardiovascular event was elevated in the 1-7 days after infection (IR 7.14 [95% CI 6.06-8.41]) and, while the effect size tapered, the risk remained for 15-28 days after infection (1.74 [1.33-2.26]). Risks were similar for individual event type, differing by level of cardiovascular risk, and in wave one and two of the pandemic. . SARS-CoV-2 infection is associated with early elevations in the risk of first acute cardiovascular event, across cardiovascular risk levels and in both wave one and two of the pandemic. Prevention of COVID-19 is important to avert cardiovascular complications.

Development and validation of a rapid visual technique for left ventricular hypertrophy detection from the electrocardiogram.

Left ventricular hypertrophy (LVH) detection techniques on by electrocardiogram (ECG) are cumbersome to remember with modest performance. This study validated a rapid technique for LVH detection and measured its performance against other techniques. This was a retrospective cohort study of patients at Stanford Health Care who received ECGs and resting transthoracic echocardiograms (TTE) from 2006 through 2018. The novel technique, Witteles-Somani (WS), assesses for S- and R-wave overlap on adjacent precordial leads. The WS, Sokolow-Lyon, Cornell, and Peguero-Lo Presti techniques were algorithmically implemented on ECGs. Classification metrics, receiver-operator curves, and Pearson correlations measured performance. Age- and sex-adjusted Cox proportional hazard models evaluated associations between incident cardiovascular outcomes and each technique. A total of 53,333 ECG-TTE pairs from 18,873 patients were identified. Of all ECG-TTE pairs, 21,638 (40.6%) had TTE-diagnosed LVH. The WS technique had a sensitivity of 0.46, specificity of 0.66, and AUROC of 0.56, compared to Sokolow-Lyon (AUROC 0.55), Cornell (AUROC 0.63), and Peguero-Lo Presti (AUROC 0.63). Patients meeting LVH by WS technique had a higher risk of cardiovascular mortality [HR 1.18, 95% CI (1.12, 1.24), P < 0.001] and a higher risk of developing any cardiovascular disease [HR 1.29, 95% CI (1.22, 1.36), P < 0.001], myocardial infarction [HR 1.60, 95% CI (1.44, 1.78), P < 0.005], and heart failure [HR 1.24, 95% CI (1.17, 1.32), P < 0.001]. The WS criteria is a rapid visual technique for LVH detection with performance like other LVH detection techniques and is associated with incident cardiovascular outcomes.

Protein Biomarkers of Early Menopause and Incident Cardiovascular Disease.

Background Premature and early menopause are independently associated with greater risk of cardiovascular disease (CVD). However, mechanisms linking age of menopause with CVD remain poorly characterized. Methods and Results We measured 71 circulating CVD protein biomarkers in 1565 postmenopausal women enrolled in the FHS (Framingham Heart Study). We examined the association of early menopause with biomarkers and tested whether early menopause modified the association of biomarkers with incident cardiovascular outcomes (heart failure, major CVD, and all-cause death) using multivariable-adjusted linear regression and Cox models, respectively. Among 1565 postmenopausal women included (mean age 62 years), 395 (25%) had a history of early menopause. Of 71 biomarkers examined, we identified 7 biomarkers that were significantly associated with early menopause, of which 5 were higher in women with early menopauseincluding adrenomedullin and resistin, and 2 were higher in women without early menopauseincluding insulin growth factor-1 and CNTN1 (contactin-1) (Benjamini-Hochberg adjusted P<0.1 for all). Early menopause also modified the association of specific biomarkers with incident cardiovascular outcomes including adrenomedullin (Pint<0.05). Conclusions Early menopause is associated with circulating levels of CVD protein biomarkers and appears to modify the association between select biomarkers with incident cardiovascular outcomes. Identified biomarkers reflect several distinct biological pathways, including inflammation, adiposity, and neurohormonal regulation. Further investigation of these pathways may provide mechanistic insights into the pathogenesis, prevention, and treatment of early menopause-associated CVD.

Risk of Cardiovascular Disease After COVID-19 Diagnosis Among Adults With and Without Diabetes.

Background Growing evidence suggests incident cardiovascular disease (CVD) may be a long-term outcome of COVID-19 infection, and chronic diseases, such as diabetes, may influence CVD risk associated with COVID-19. We evaluated the postacute risk of CVD >30 days after a COVID-19 diagnosis by diabetes status. Methods and Results We included adults ≥20 years old with a COVID-19 diagnosis from March 1, 2020 through December 31, 2021 in a retrospective cohort study from the IQVIA PharMetrics Plus insurance claims database. A contemporaneous control group comprised adults without recorded diagnoses for COVID-19 or other acute respiratory infections. Two historical control groups comprised patients with or without an acute respiratory infection. Cardiovascular outcomes included cerebrovascular disorders, dysrhythmia, inflammatory heart disease, ischemic heart disease, thrombotic disorders, other cardiac disorders, major adverse cardiovascular events, and any CVD. The total sample comprised 23 824 095 adults (mean age, 48.4 years [SD, 15.7 years]; 51.9% women; mean follow-up, 8.5 months [SD, 5.8 months]). In multivariable Cox regression models, patients with a COVID-19 diagnosis had a significantly greater risk of all cardiovascular outcomes compared with patients without a diagnosis of COVID-19 (hazard ratio [HR], 1.66 [1.62-1.71], with diabetes; HR, 1.75 [1.73-1.78], without diabetes). Risk was attenuated but still significant for the majority of outcomes when comparing patients with COVID-19 to both historical control groups. Conclusions In patients with COVID-19 infection, postacute risk of incident cardiovascular outcomes is significantly higher than among controls without COVID-19, regardless of diabetes status. Therefore, monitoring for incident CVD may be essential beyond the first 30 days after a COVID-19 diagnosis.

Atlas of gut microbe-derived products from aromatic amino acids and risk of cardiovascular morbidity and mortality.

Precision microbiome modulation as a novel treatment strategy is a rapidly evolving and sought goal. The aim of this study is to determine relationships among systemic gut microbial metabolite levels and incident cardiovascular disease risks to identify gut microbial pathways as possible targets for personalized therapeutic interventions. Stable isotope dilution mass spectrometry methods to quantitatively measure aromatic amino acids and their metabolites were used to examine sequential subjects undergoing elective diagnostic cardiac evaluation in two independent cohorts with longitudinal outcome data [US (n = 4000) and EU (n = 833) cohorts]. It was also used in plasma from humans and mice before vs. after a cocktail of poorly absorbed antibiotics to suppress gut microbiota. Multiple aromatic amino acid-derived metabolites that originate, at least in part, from gut bacteria are associated with incident (3-year) major adverse cardiovascular event (MACE) risks (myocardial infarction, stroke, or death) and all-cause mortality independent of traditional risk factors. Key gut microbiota-derived metabolites associated with incident MACE and poorer survival risks include: (i) phenylacetyl glutamine and phenylacetyl glycine (from phenylalanine); (ii) p-cresol (from tyrosine) yielding p-cresol sulfate and p-cresol glucuronide; (iii) 4-OH-phenyllactic acid (from tyrosine) yielding 4-OH-benzoic acid and 4-OH-hippuric acid; (iv) indole (from tryptophan) yielding indole glucuronide and indoxyl sulfate; (v) indole-3-pyruvic acid (from tryptophan) yielding indole-3-lactic acid and indole-3-acetyl-glutamine, and (vi) 5-OH-indole-3-acetic acid (from tryptophan). Key gut microbiota-generated metabolites derived from aromatic amino acids independently associated with incident adverse cardiovascular outcomes are identified, and thus will help focus future studies on gut-microbial metabolic outputs relevant to host cardiovascular health.