Associations of metabolic syndrome with lung function decline and clinical respiratory outcomes: the NHLBI Pooled Cohort Study

Abstract

Background: Whether metabolic syndrome (MetS) increases the risk of chronic lung diseases remains uncertain. We aimed to test whether MetS was associated with lung function and clinical respiratory outcomes.

Methods: Data were harmonised from six US general population-based prospective cohorts. Participants with baseline airflow limitation (forced expiratory volume in 1 s (FEV₁):forced vital capacity (FVC) <0.70), restriction (FEV₁:FVC ≥0.7, FVC <80%), clinical chronic lower respiratory disease (CLRD) or cardiovascular disease were excluded. MetS was defined at baseline as the presence of at least three of the following: central obesity, high triglycerides, low high-density lipoprotein cholesterol, high blood pressure (BP) and high fasting glucose. Associations with lung function decline and incident clinical respiratory events were tested in linear mixed models and Cox models, respectively, adjusted for sociodemographic, anthropometric, smoking and clinical factors. The five subcomponents of MetS were evaluated separately in secondary analyses.

Results: Of 15 728 participants (mean age 49.6 years, 57.6% female, 68.6% White, 27.0% Black), 4422 (28.1%) had MetS. In fully adjusted models that included body weight, MetS was associated with greater rate of FVC decline (-0.89 mL·year^-1, 95% CI -1.73- -0.05) and incident restriction (1085 cases, hazard ratio 1.52, 95% CI 1.30-1.77), but not FEV₁ decline, incident airflow limitation or clinical respiratory outcomes. Among the subcomponents of MetS, central obesity, high BP and high fasting glucose were associated with incident restriction, while high BP alone was associated with incident airflow limitation, CLRD-related events and respiratory-related mortality.

Conclusions: MetS was associated with accelerated FVC decline and incident restriction, but not incident obstruction, in healthy adults.

FIGURE 1

Flowchart of study selection. ARIC: Atherosclerosis Risk in Communities; CARDIA: Coronary Artery Risk Development in Young Adults; CHD: coronary heart disease; CHS: Cardiovascular Health Study; CLRD: chronic lower respiratory disease; FHS: Framingham Heart Study; HCHS: Hispanic Community Health Study; Health ABC: The Health, Aging and Body Composition Study; JHS: Jackson Heart Study; MESA: multi-ethnic study of atherosclerosis; MetS: metabolic syndrome; NHLBI: National Heart, Lung, and Blood Institute.

FIGURE 2

a) Forced vital capacity decline, estimated from the slope for metabolic syndrome (MetS)×time (age at measurement) using a linear mixed model, with cohort-specific unstructured covariance matrices that account for both between- and within-participant variability. The model was adjusted for time-variant covariates (age, age², height², weight and smoking status) and time-invariant covariates (baseline age, centred birth year, sex, race and ethnicity, educational attainment, study, site, and smoking pack-years), as well as age interaction with time-invariant covariates. Negative coefficients represent a faster annual decline in lung function measurements. b) Incident restriction, estimated using Cox proportional hazards regression with a strata term for the cohort. The model was adjusted for the following covariates except for the covariates stratified in each model: baseline age, sex, race and ethnicity, educational attainment, height, weight, centred birth year, site, smoking status, and smoking pack-years. The interaction was tested with multiplicative interaction terms of MetS and each covariate in the same model. Participants with a body mass index (BMI) <18.5 were excluded from the subgroup analysis because there were no cases of MetS in this underweight category, rendering analysis impossible. β: beta regression; HR: hazard ratio; PRISm: preserved ratio impaired spirometry.