Associations of LDL and HDL cholesterol with lung function decline and risk of airflow obstruction in a community-based cohort

Dyslipidemia may affect pulmonary function through systemic inflammation and metabolic pathways; however, longitudinal evidence remains limited. This study examined the associations of baseline low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels with subsequent rates of lung function decline and the incidence of airflow obstruction in a community-based observational cohort, Korean Genome and Epidemiology Study (KoGES). We analyzed 7381 participants without baseline airflow obstruction. LDL cholesterol was categorized as ≤ 130 mg/dL (LDL_low), 130-160 mg/dL (LDL_medium), and > 160 mg/dL (LDL_high), while HDL cholesterol was classified as ≤ 50 mg/dL (HDLlow) and > 50 mg/dL (HDL_high). Annual changes in FEV₁ and FVC were estimated using linear mixed-effects models, and Cox proportional hazards models were applied to assess the risk of incident airflow obstruction. Compared with the LDL_low group, participants in the LDL_high group had a slower annual decline in FEV₁ (- 37.21 mL/year, 95% CI: -39.00 to - 35.43) versus (- 40.39 mL/year, 95% CI: -40.94 to - 39.84) and FVC (- 30.06 mL/year, 95% CI: -32.18 to - 27.94) versus (- 35.78 mL/year, 95% CI: -36.43 to - 35.13), respectively (both p < 0.001). Higher LDL levels were significantly associated with a lower risk of incident airflow obstruction (adjusted HR: 0.71, 95% CI: 0.54-0.92). In contrast, higher HDL levels were associated with a faster FEV₁ decline (- 41.34 mL/year, 95% CI: -42.44 to - 40.24) compared with HDL_low (- 37.84 mL/year, 95% CI -38.46 to - 37.22, p < 0.001), but not with FVC decline or incident airflow obstruction. Higher baseline LDL cholesterol levels were associated with a slower decline in lung function and a lower risk of developing airflow obstruction, whereas higher HDL cholesterol levels were associated with an accelerated decline in FEV₁. These findings highlight complex, potentially bidirectional relationships between lipid metabolism and respiratory outcomes, warranting further mechanistic research. Importantly, these associations should not be interpreted as implying that high LDL is beneficial for general health.