Biomarker-Based Risk Prediction of Incident Heart Failure in Pre-Diabetes and Diabetes

Abstract

Objectives: 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.

Background: Risk stratification tools to identify patients with diabetes and pre-diabetes at highest risk for HF are needed to inform cost-effective allocation of preventive therapies. Whether a biomarker score can meaningfully stratify HF risk is unknown.

Methods: Participants free of cardiovascular disease from 3 cohort studies (ARIC [Atherosclerosis Risk In Communities], DHS [Dallas Heart Study], and MESA [Multi-Ethnic Study of Atherosclerosis]) were included. An integer-based biomarker score included high-sensitivity cardiac troponin T ≥6 ng/l, N-terminal pro-B-type natriuretic peptide ≥125 pg/ml, high-sensitivity C-reactive protein ≥3 mg/l, and left ventricular hypertrophy by electrocardiography, with 1 point for each abnormal parameter. The 5-year risk of HF was estimated among participants with diabetes and pre-diabetes across biomarker score groups (0 to 4).

Results: The primary analysis included 6,799 participants with dysglycemia (diabetes: 33.2%; pre-diabetes: 66.8%). The biomarker score demonstrated good discrimination and calibration for predicting 5- and 10-year HF risk among pre-diabetes and diabetes cohorts. The 5-year risk of HF among subjects with a biomarker score of ≤1 was low and comparable to participants with euglycemia (0.78%). The 5-year risk for HF increased in a graded fashion with an increasing biomarker score, with the highest risk noted among those with scores of ≥3 (diabetes: 12.0%; pre-diabetes: 7.8%). The estimated number of HF events that could be prevented using a sodium-glucose cotransporter-2 inhibitor per 1,000 treated subjects over 5 years was 11 for all subjects with diabetes and ranged from 4 in the biomarker score zero group to 44 in the biomarker score ≥3 group.

Conclusions: Among adults with diabetes and pre-diabetes, a biomarker score can stratify HF risk and inform allocation of HF prevention therapies.

Keywords: SGLT-2 inhibitors; biomarkers; diabetes; pre-diabetes; risk prediction.

Figure 1.. Multivariable adjusted association of biomarker score groups with risk of HF among participants with diabetes and prediabetes.

Covariates included demographics (age, sex, race), cardiovascular risk factors (smoking status, body mass index, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, estimated glomerular filtration rate, fasting plasma glucose), medication use (statin, anti-hypertensive medication), study cohort.

Figure 2.. 5-year Kaplan Meier estimates for heart failure risk among participants with diabetes and prediabetes stratified by biomarker score group.

The red dotted line represents the 5-year Kaplan Meier estimate for heart failure in participants with euglycemia (0.78%).

Central Illustration:. Biomarker risk score to identify patient with diabetes who are a high risk of heart failure and may benefit from SGLT-2 inhibitors.

The black dotted line represents the number of HF events prevented per 1,000 participants with diabetes, irrespective of biomarker score group, treated with an SGLT-2 inhibitor for 5 years (11 HF events). Based on a pooled analysis of SGLT-2 inhibitor cardiovascular outcome trials, a 36% relative risk reduction in HF was used to calculate the absolute risk reduction at 5-years.(7) Abbreviations: HF = heart failure; SGLT-2 = sodium-glucose cotransporter-2.