Skeletal Muscle Mass Modifies the Prognostic Impact of LDL Cholesterol in Chronic Heart Failure

Dyslipidaemia is among the major risk factors for atherosclerotic cardiovascular disease. Paradoxically, higher cholesterol levels are associated with better survival in heart failure (HF) of any aetiology. Because cholesterol is an integral component of skeletal muscle structure, one possible explanation involves the interplay between lipid metabolism and skeletal muscle health. Using data from the Studies Investigating Comorbidities Aggravating Heart Failure, we investigated whether an association exists between low-density lipoprotein cholesterol (LDL-C) levels and all-cause mortality in patients with chronic HF in the context of skeletal muscle mass.

A total of 241 patients with chronic HF (68 ± 11 years, 80% male, left ventricular ejection fraction 39% ± 13%) were enrolled. LDL-C levels were divided into low and high based on the median value (93 mg/dL). The appendicular skeletal muscle mass index (ASMI) was assessed using a dual-energy X-ray absorptiometry scan and divided into high and low based on the sex-specific median value (men = 7.97 kg/m², women = 6.87 kg/m²). Patients were divided into four groups based on median LDL-C levels and ASMI values.

During a median follow-up of 6.3 years, 95 patients (39%) died. There were differences in mortality between the four groups, with the highest mortality in patients with low LDL-C levels and low ASMI and the lowest mortality in patients with high LDL-C levels and high ASMI (p = 0.002, by log-rank). The low LDL-C group had higher mortality compared with the high LDL-C group (46% vs. 33%, p = 0.01, by log-rank). Multivariate Cox proportional hazard analysis confirmed the association between the low LDL-C group and higher mortality (adjusted hazard ratio [aHR] 1.65 [1.00-2.72], p = 0.04). This prognostic impact of low LDL-C appeared greater in the low ASMI group than in the high ASMI group (56% vs. 37%, p = 0.01, and 36% vs. 28%, p = 0.28, by log-rank: p for interaction = 0.47). In the low ASMI group, lower LDL-C levels were predictors of mortality in multivariate Cox proportional hazard models (aHR 1.46-1.48 per 1 SD decrease in LDL-C, all p < 0.05).

In patients with chronic HF, lower LDL-C levels were associated with higher mortality, especially in the low ASMI group. These findings suggest that low cholesterol levels may exacerbate skeletal muscle loss, potentially creating a vicious cycle that worsens patient outcomes. Lipid-modulating strategies could help mitigate muscle wasting in HF.