Association between LDL-C levels and outcomes in patients with heart failure with preserved ejection fraction: a real-world study
S Jiang, L Li, G Aa, X Qian, P Sun, X Zhou, Q YangAbstract
Background
Although the correlation between elevated low-density lipoprotein cholesterol (LDL-C) levels and heightened cardiovascular risk is well-established, its association with long-term prognosis in patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely understood.
Purpose
This study aimed to investigate, in patients with HFpEF: 1) the association between LDL-C levels at the time of first HFpEF diagnosis and clinical outcomes; and 2) the interaction of different comorbidity patterns on this association.
Methods
Using electronic medical record data, this real-world study examined the relationship between baseline LDL-C levels and 3-year all-cause mortality in hospitalized patients with HFpEF. Multivariable-adjusted Cox model was used to calculated hazard ratio (HR) and 95% confidence interval (CI). Hierarchical clustering of 15 conditions was employed to identify patient subgroups, and the association of LDL-C with 3-year all-cause mortality was examined within each identified patterns.
Results
A total of 44,249 patients (average 70.8 years old) were enrolled and categorized into five groups based on baseline LDL-C levels: <70 mg/dL, 70-100 mg/dL, 100-130 mg/dL, 130-160 mg/dL, and >160 mg/dL. During 3-year follow-up, the all-cause mortality rates were 21.1%, 17.1%, 15.6%, 14.4%, and 15.4% in these groups, respectively. In Cox regression analysis, a U-shaped association was observed between baseline LDL-C and 3-year mortality. Compared to patients with LDL-C 100-130 mg/dL, both lower (<70 mg/dL) and higher (130-160 and >160 mg/dL) LDL-C levels were associated with increased mortality risk (HR 1.14 [95%CI: 1.06-1.22]; HR 1.08 [95%CI: 1.00-1.17]; HR 1.29 [95%CI: 1.17-1.41], respectively). Hierarchical clustering identified six distinct patterns: Cardiostructural-Rhythmic (Pattern 1, n = 297, 0.67%), Immune-Hematic-Respiratory (Pattern 2, n = 2,388, 5.40%), Cardiometabolic (Pattern 3, n = 3,546, 8.01%), Combined (Pattern 4, n = 1,894, 4.28%), Non-Clustered (Pattern 5, n = 1,958, 4.42%), and No Multimorbidity (Pattern 6, n = 34,166, 77.2%). Compared with No Multimorbidity patients, those in other five identified patterns were associated with a 60% (Pattern 1), 104% (Pattern 2), 10% (Pattern 3), 98% (Pattern 4), and 31% (Pattern 5) higher risk of 3-year all-cause mortality, respectively. In Pattern 2, LDL-C < 70 mg/dL (versus 100-130 mg/dL) was associated with a 28% increased risk of 3-year mortality (HR 1.28 [95%CI: 1.04-1.57]), while higher LDL-C levels showed no such association. Conversely, in Pattern 3, no significant difference in risk was observed for patients with lower LDL-C levels, but LDL-C >160 mg/dL was associated with increased mortality (HR 1.43 [95%CI: 1.06-1.94]).
Conclusion
A U-shaped association between LDL-C levels and 3-year mortality was observed in the overall HFpEF population. Notably, this association was modified by the presence of different comorbidity patterns.Survival curve and forest plot of mortalityComorbidity patterns and stratified analysis