**Background:** Heart failure (HF) is a growing public health burden with rising incidence in aging populations. Handgrip strength (HGS) is a simple, non-invasive measure of overall muscle function, but evidence linking HGS to HF has been sparse and conflicting. Some prior studies found no significant association, while others suggested an inverse relationship. This study aimed to clarify the association between HGS and HF in a nationally representative sample of US adults aged 45 years and older.
**Methods:** Data were drawn from the NHANES 2011–2014 cycles, the only cycles with HGS measurements available. After excluding participants with cognitive impairment (n=74), depression (n=840), missing HGS data (n=4,372), missing HF data (n=4,922), or missing covariates (n=356), the final analytic sample included 4,524 participants. HGS was measured using a handgrip dynamometer (Model T.K.K.5401), with the sum of the largest reading from each hand expressed in kilograms. HF was defined by a self-reported 'yes' to the question 'Has a doctor or other health professional ever told you that you had heart failure?' Covariates included age, gender, race, income (poverty income ratio), education, body mass index (BMI), smoking status, drinking status, diabetes, hypertension, stroke, vigorous physical activity, total energy intake, total protein intake, total sugars intake, and total fat intake. Multiple logistic regression models and a generalized additive model were used to assess the association. Subgroup analyses were performed across 16 strata.
**Key Results:** Among 4,524 participants (mean age 61.78 years, 50.22% male), 189 (4.18%) had HF (106 men, 83 women). HGS was linearly associated with HF (P for non-linearity = 0.438). In the fully adjusted model (Model II), HGS as a continuous variable was negatively associated with HF (OR 0.97, 95% CI 0.96–0.99; P < 0.001). When analyzed by quintiles, compared to the lowest quintile (≤48.40 kg), the odds ratios for HF were: Q2 (48.50–58.10 kg): OR 1.12 (95% CI 0.70–1.77); Q3 (58.20–70.20 kg): OR 0.89 (95% CI 0.53–1.49); Q4 (70.30–85.70 kg): OR 0.53 (95% CI 0.29–0.98); Q5 (≥85.80 kg): OR 0.18 (95% CI 0.08–0.43); P for trend < 0.001. The highest quintile was associated with an 82% lower incidence of HF. Subgroup analyses showed the negative association remained stable across all strata (all P for interaction > 0.05), including age, gender, race, income, education, BMI, diabetes, hypertension, stroke, smoking, drinking, physical activity, and all nutrient intake levels.
**Clinical Implications:** This study provides evidence that higher HGS is independently and negatively associated with HF in US adults aged 45 and older, after comprehensive adjustment for demographic, clinical, lifestyle, and nutritional confounders. The findings suggest that HGS, a quick and inexpensive clinical measurement, could serve as a practical screening tool to identify individuals at higher risk for HF. The results also highlight the potential role of muscle function in cardiovascular health, though the cross-sectional design precludes causal inference. The authors propose several mechanistic pathways including inflammation/oxidative stress, apoptosis, abnormal glucose metabolism/insulin resistance, and myokine signaling. Limitations include the cross-sectional design (cannot establish causality), reliance on self-reported HF diagnosis (no echocardiographic or biomarker confirmation), potential recall bias, and limited generalizability to younger or less healthy populations. Prospective studies and intervention trials are needed to confirm these findings and explore whether muscle-strengthening interventions could reduce HF risk.