Advancing Cardiovascular Risk Assessment with Artificial Intelligence: Opportunities and Implications in North Carolina.

Cardiovascular disease mortality is increasing in North Carolina with persistent inequality by race, income, and location. Artificial intelligence (AI) can repurpose the widely available electrocardiogram (ECG) for enhanced assessment of cardiac dysfunction. By identifying accelerated cardiac aging from the ECG, AI offers novel insights into risk assessment and prevention.

The Metabolic Vulnerability Index: A Novel Marker for Mortality Prediction in Heart Failure.

BACKGROUND: Inflammation and protein energy malnutrition are associated with heart failure (HF) mortality. The metabolic vulnerability index (MVX) is derived from markers of inflammation and malnutrition and measured by nuclear magnetic resonance spectroscopy. MVX has not been examined in HF. OBJECTIVES: The authors sought to examine the prognostic value of MVX in patients with HF. METHODS: The authors prospectively assembled a population-based cohort of patients with HF from 2003 to 2012 and measured MVX scores with a nuclear magnetic resonance scan from plasma collected at enrollment. Patients were divided into 4 MVX score groups and followed until March 31, 2021. RESULTS: The authors studied 1,382 patients (median age: 78 years; 48% women). The median MVX score was 64.6. Patients with higher MVX were older, more likely to be male, have atrial fibrillation, have higher NYHA functional class, and have HF duration of >18 months. Higher MVX was associated with mortality independent of Meta-analysis Global Group in Chronic Heart Failure score, ejection fraction, and other prognostic biomarkers. Compared to those with the lowest MVX, the HRs for MVX groups 2, 3, and 4 were 1.2 (95% CI: 0.9-1.4), 1.6 (95% CI: 1.3-2.0), and 1.8 (95% CI: 1.4-2.2), respectively (Ptrend < 0.001). Measures of model improvement document the added value of MVX in HF for classifying the risk of death beyond the Meta-analysis Global Group in Chronic Heart Failure score and other biomarkers. CONCLUSIONS: In this HF community cohort, MVX was strongly associated with mortality independently of established clinical factors and improved mortality risk classification beyond clinically validated markers. These data underscore the potential of MVX to stratify risk in HF.

Circulating ketone bodies and mortality in heart failure: a community cohort study.

Background: The relationship between ketone bodies (KB) and mortality in patients with heart failure (HF) syndrome has not been well established. Objectives: The aim of this study is to assess the distribution of KB in HF, identify clinical correlates, and examine the associations between plasma KB and all-cause mortality in a population-based HF cohort. Methods: The plasma KB levels were measured by nuclear magnetic resonance spectroscopy. Multivariable linear regression was used to examine associations between clinical correlates and KB levels. Proportional hazard regression was employed to examine associations between KB (represented as both continuous and categorical variables) and mortality, with adjustment for several clinical covariates. Results: Among the 1,382 HF patients with KB measurements, the median (IQR) age was 78 (68, 84) and 52% were men. The median (IQR) KB was found to be 180 (134, 308) µM. Higher KB levels were associated with advanced HF (NYHA class III-IV) and higher NT-proBNP levels (both P < 0.001). The median follow-up was 13.9 years, and the 5-year mortality rate was 51.8% [95% confidence interval (CI): 49.1%-54.4%]. The risk of death increased when KB levels were higher (HRhigh vs. low group 1.23; 95% CI: 1.05-1.44), independently of a validated clinical risk score. The association between higher KB and mortality differed by ejection fraction (EF) and was noticeably stronger among patients with preserved EF. Conclusions: Most patients with HF exhibited KB levels that were consistent with those found in healthy adults. Elevated levels of KB were observed in patients with advanced HF. Higher KB levels were found to be associated with an increased risk of death, particularly in patients with preserved EF.

Incremental Value of a Metabolic Risk Score for Heart Failure Mortality: A Population-Based Study.

BACKGROUND: Heart failure is heterogeneous syndrome with persistently high mortality. Nuclear magnetic resonance spectroscopy enables high-throughput metabolomics, suitable for precision phenotyping. We aimed to use targeted metabolomics to derive a metabolic risk score (MRS) that improved mortality risk stratification in heart failure. METHODS: Nuclear magnetic resonance was used to measure 21 metabolites (lipoprotein subspecies, branched-chain amino acids, alanine, GlycA (glycoprotein acetylation), ketone bodies, glucose, and citrate) in plasma collected from a heart failure community cohort. The MRS was derived using least absolute shrinkage and selection operator penalized Cox regression and temporal validation. The association between the MRS and mortality and whether risk stratification was improved over the Meta-Analysis Global Group in Chronic Heart Failure clinical risk score and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels were assessed. RESULTS: The study included 1382 patients (median age, 78 years, 52% men, 43% reduced ejection fraction) with a 5-year survival rate of 48% (95% CI, 46%-51%). The MRS included 9 metabolites measured. In the validation data set, a 1 standard deviation increase in the MRS was associated with a large increased rate of death (hazard ratio, 2.2 [95% CI, 1.9-2.5]) that remained after adjustment for Meta-Analysis Global Group in Chronic Heart Failure score and NT-proBNP (hazard ratio, 1.6 [95% CI, 1.3-1.9]). These associations did not differ by ejection fraction. The integrated discrimination and net reclassification indices, and Uno's C statistic, indicated that the addition of the MRS improved discrimination over Meta-Analysis Global Group in Chronic Heart Failure and NT-proBNP. CONCLUSIONS: This MRS developed in a heart failure community cohort was associated with a large excess risk of death and improved risk stratification beyond an established risk score and clinical markers.

Lipoprotein Insulin Resistance Score and Mortality Risk Stratification in Heart Failure.

BACKGROUND: Higher total serum cholesterol is associated with lower mortality in heart failure. Evaluating associations between lipoprotein subfractions and mortality among people with heart failure may provide insights into this observation. METHODS: We prospectively enrolled a community cohort of people with heart failure from 2003 to 2012 and assessed vital status through 2021. Plasma collected at enrollment was used to measure lipoprotein subfractions via nuclear magnetic resonance spectroscopy. A composite score of 6 lipoprotein subfractions was generated using the lipoprotein insulin resistance index (LP-IR) algorithm. Using covariate-adjusted proportional hazards regression models, we evaluated associations between LP-IR score and all-cause mortality. RESULTS: Among 1382 patients with heart failure (median follow-up 13.9 years), a one-standard-deviation (SD) increment in LP-IR score was associated with lower mortality (hazard ratio [HR] 0.93; 95% confidence interval [CI], 0.97-0.99). Among LP-IR parameters, mean high-density lipoprotein (HDL) particle size was significantly associated with lower mortality (HR per 1-SD decrement in mean HDL particle size = 0.83; 95% CI, 0.78-0.89), suggesting that the inverse association between LP-IR score and mortality may be driven by smaller mean HDL particle size. CONCLUSIONS: LP-IR score was inversely associated with mortality among patients with heart failure and may be driven by smaller HDL particle size.

Frailty and Metabolic Vulnerability in Heart Failure: A Community Cohort Study.

BACKGROUND: Frailty is common in heart failure (HF) and is associated with death but not routinely captured clinically. Frailty is linked with inflammation and malnutrition, which can be assessed by a novel plasma multimarker score: the metabolic vulnerability index (MVX). We sought to evaluate the associations between frailty and MVX and their prognostic impact. METHODS AND RESULTS: In an HF community cohort (2003-2012), we measured frailty as a proportion of deficits present out of 32 physical limitations and comorbidities, MVX by nuclear magnetic resonance spectroscopy, and collected extensive longitudinal clinical data. Patients were categorized by frailty score (≤0.14, >0.14 and ≤0.27, >0.27) and MVX score (≤50, >50 and ≤60, >60 and ≤70, >70). Cox models estimated associations of frailty and MVX with death, adjusted for Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score and NT-proBNP (N-terminal pro-B-type natriuretic peptide). Uno's C-statistic measured the incremental value of MVX beyond frailty and clinical factors. Weibull's accelerated failure time regression assessed whether MVX mediated the association between frailty and death. We studied 985 patients (median age, 77; 48% women). Frailty and MVX were weakly correlated (Spearman's ρ=0.21). The highest frailty group experienced an increased rate of death, independent of MVX, MAGGIC score, and NT-proBNP (hazard ratio, 3.3 [95% CI, 2.5-4.2]). Frailty improved Uno's c-statistic beyond MAGGIC score and NT-proBNP (0.69-0.73). MVX only mediated 3.3% and 4.5% of the association between high and medium frailty groups and death, respectively. CONCLUSIONS: In this HF cohort, frailty and MVX are weakly correlated. Both independently contribute to stratifying the risk of death, suggesting that they capture distinct domains of vulnerability in HF.