Adults with hypertension and both prediabetes and subclinical myocardial injury or stress may have more than five times the risk of incident heart failure compared with those with normoglycemia and no biomarker elevation, according to a recent brief report.
Prediabetes alone, without elevation in high-sensitivity cardiac troponin I or N-terminal pro–B-type natriuretic peptide, wasn't independently associated with increased heart failure (HF) risk.
In the analysis, researchers enrolled 8,234 participants with hypertension who didn't have diabetes or prior HF and had baseline measurements of high-sensitivity cardiac troponin I (hs-cTnI) and N-terminal pro–B-type natriuretic peptide (NT-proBNP). Prediabetes was classified using fasting plasma glucose values of 100 to 125 mg/dL, subclinical myocardial injury was identified by hs-cTnI concentrations of 6 ng/L or greater in male patients and 4 ng/L or greater in female patients, and myocardial stress was defined as NT-proBNP levels of 125 pg/mL or greater. Cox proportional hazards models adjusted for demographic and clinical covariates were used to estimate HF risk across joint categories of glycemic status and biomarker elevation. When subclinical myocardial injury or stress was present, prediabetes was associated with more than ten times the risk of HF compared with those with normoglycemia and no biomarker elevation.
Over a median follow-up of 3.2 years, 122 HF events occurred, corresponding to an incidence rate of 4.6 per 1,000 person-years. In fully adjusted models, compared with patients with normoglycemia and no injury, the patients with prediabetes and myocardial injury had a 4.20-fold higher risk of HF, whereas normoglycemia with injury was associated with a 3.28-fold higher risk. Prediabetes without myocardial injury wasn't significantly associated with HF. Similar associations were observed for myocardial stress: prediabetes with stress was associated with a 5.20-fold higher risk and normoglycemia with stress with a 3.78-fold higher risk compared with normoglycemia without stress.
In a longitudinal analysis involving 7,449 participants with biomarker measurements at baseline and 12 months and excluding those who developed HF prior to 12 months, the researchers defined a 25% or greater increase in hs-cTnI or NT-proBNP as meaningful biomarker change. During a median follow-up of 2.3 years, 78 HF events occurred. The patients with prediabetes and a 25% or greater increase in hs-cTnI had a 3.05-fold higher risk of HF, and those with a similar increase in NT-proBNP had a 2.39-fold higher risk. Prediabetes without biomarker elevation or longitudinal increase wasn't associated with excess HF risk.
Limitations included the observational nature of this secondary analysis, which doesn't establish a causal relationship, and the use of a single fasting plasma glucose measurement to define prediabetes, which may have resulted in misclassification. Echocardiographic data were unavailable, limiting assessment of cardiac structure and HF phenotype. In addition, the analysis drew on the large Systolic Blood Pressure Intervention Trial cohort, which featured systematically adjudicated outcomes and detailed clinical characterization of patients with hypertension at elevated cardiovascular risk.
“Although the biomarkers largely drive this risk, prediabetes serves as a clinically meaningful modifier that may amplify vulnerability to myocardial dysfunction,” noted lead study author Arnaud D. Kaze, MD, MPH, of the Division of Cardiology in the Department of Medicine at the Banner-University Medical Center Phoenix at The University of Arizona College of Medicine, and colleagues.
Co–study author Christie M. Ballantyne, MD, reported grant funding, research support, and consulting fees from multiple pharmaceutical and diagnostic companies during the study; and co–study author Jarrett D. Berry, MD, MS, reported grant support from the National Institutes of Health, Abbott, and Roche during the study and personal fees from the Cooper Institute outside the submitted work.The study authors reported no other disclosures.
Source: JAMA Cardiology
