title: Ages at Onset of 5 Cardiometabolic Diseases Adjusting for Nonsusceptibility: Implications for the Pathogenesis of Metabolic Syndrome.
abstract: To shed light on the etiology of metabolic syndrome development, it is important to understand whether its 5 component disorders follow certain onset sequences. To explore disease progression of the syndrome, we studied the ages at onset of 5 cardiometabolic diseases: abdominal obesity, diabetes, hypertension, hypertriglyceridemia, and hypo-α-lipoproteinemia. In analyzing longitudinal data from the Cardiovascular Disease Risk Factors Two-Township Study (1989-2002) in Taiwan, we adjusted for nonsusceptibility, utilizing the logistic-accelerated failure time location-scale mixture regression models for left-truncated and interval-censored data to simultaneously estimate the associations of township and sex with the susceptibility probability and the age-at-onset distribution of susceptible individuals for each disease. We then validated the onset sequences of 5 cardiometabolic diseases by comparing the overall probability density curves across township-sex strata. Visualization of these curves indicates that women tended to have onsets of abdominal obesity and hypo-α-lipoproteinemia in young adulthood, hypertension and hypertriglyceridemia in middle age, and diabetes later; men tended to have onsets of abdominal obesity, hypo-α-lipoproteinemia, and hypertriglyceridemia in young adulthood, hypertension in middle age, and diabetes later. Different onset patterns of abdominal obesity, hypo-α-lipoproteinemia, and male hypertension were identified between townships. Our proposed method provides a novel strategy for investigating both pathogenesis and preventive measures of complex syndromes.
authors.forename: Yuh-Chyuan
authors.initials: YC
authors.lastname: Tsay
authors.forename: Chen-Hsin
authors.initials: CH
authors.lastname: Chen
authors.forename: Wen-Harn
authors.initials: WH
authors.lastname: Pan
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000453:epidemiology / Q000209:etiology; D048909:Diabetes Complications / Q000453:epidemiology / Q000209:etiology; D003920:Diabetes Mellitus / Q000453:epidemiology / Q000209:etiology; D018450:Disease Progression; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000453:epidemiology / Q000209:etiology; D015228:Hypertriglyceridemia / Q000150:complications / Q000453:epidemiology / Q000209:etiology; D052456:Hypoalphalipoproteinemias / Q000150:complications / Q000453:epidemiology / Q000209:etiology; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D024821:Metabolic Syndrome / Q000453:epidemiology / Q000209:etiology*; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000150:complications / Q000453:epidemiology / Q000209:etiology; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
keywords: age at onset; cardiometabolic disease; interval censoring; left truncation; metabolic syndrome; mixture regression model; nonsusceptibility; right censoring