Abstract
Background: Cardiovascular disease (CVD) is a complex disease resulting from multiscale risk factors including genetics, age, and psychosocial factors (PSFs) such as depression and social isolation. However, previous research has lacked in operationalizing multiscale risk factors to determine individual and interactive associations over the life course. Therefore, this study aimed to evaluate individual and interactive associations of multiscale risk factors for CVD outcomes including genetics and PSFs at middle and older-aged stages of the life course.Methods: Baseline data from the Canadian Longitudinal Study on Aging (CLSA; n = 9,892 with genome-wide genotyping data) was used for this investigation. A 39 single nucleotide polymorphism polygenic risk score (PRS) for CVD was constructed. PSFs consisted of: (1) Depressive symptoms categorized into: “none” (Group 1, reference), “current” (Group 2), “clinical depression with no current symptoms” (Group 3), and “potential, recurrent depression” (Group 4); and (2) Social isolation index as a binary variable comprised of marital status, living arrangements, retirement status, contacts, and social participation. Heart-related disorders (HRD: myocardial infarction, angina and heart disease) was the primary outcome of interest and peripheral/vascular-related disorders (PVRD: stroke, peripheral vascular disease and hypertension) was the secondary outcome. Multivariable logistic regression models adjusted for socio-demographic factors were conducted stratified by age group (middle-aged: 45–69 years, older-aged: ≥70 years).Results: PRS was associated with HRD among middle- and older-aged participants [OR (95% confidence interval)] [1.06 (1.03–1.08), 1.06 (1.03–1.08), respectively]. Most depressive symptoms groups compared to the reference associated with HRD and PVRD, but only Group 4 associated with PVRD among older-aged [1.69 (1.08–2.64)]. Social isolation was associated with only PVRD among middle-aged [1.84 (1.04–3.26)]; however, socially isolated CLSA participants were underrepresented in the genotyped cohort (1.2%). No significant PRS*PSFs interactions were observed.Conclusions: Genetics and PSFs are independently associated with CVD. Varying observations across age groups underscores the need to advance research on multiscale risk factors operating both at a given point in time and over the life course. Future cohort studies may benefit from use of mobile assessment units to enable better reach to socially isolated participants for collection of biospecimens.
Highlights
Cardiovascular disease (CVD) is the leading cause of death worldwide, accounting for nearly 30% of deaths globally, and the second leading cause of death in Canada [1, 2]
While Genome-wide association studies (GWAS) with CVD outcomes have predominantly been conducted among cohorts of middle-aged individuals, emerging evidence suggests that effects of genetic variation on health outcomes may dampen as individuals approach the later stages of the life course [9]
Given the growing recognition of the role of psychosocial well-being in chronic disease risk [3], psychosocial factors (PSFs) warrant consideration as possible moderators of the associations between genetic susceptibility to CVD and CVD outcomes, as they represent environmental contributors to CVD that are upstream of lifestyle which has been reported to be a modifier of the association between genetic susceptibility to CVD and CVD outcomes [6]
Summary
Cardiovascular disease (CVD) is the leading cause of death worldwide, accounting for nearly 30% of deaths globally, and the second leading cause of death in Canada [1, 2]. Multiscale risk factors consider combinations of factors that are involved along the pathway of disease pathogenesis and represent a more all encompassing approach to studying disease risk [4] This investigation assessed the associations between CVD and multiscale risk factors of genetics, psychosocial factors (PSFs) and life course stage. The objective of the present study was to assess individual and interactive associations of PSFs (depression and social isolation) and polygenic risk of CAD with CVD outcomes among middleaged and older adults. Cardiovascular disease (CVD) is a complex disease resulting from multiscale risk factors including genetics, age, and psychosocial factors (PSFs) such as depression and social isolation. This study aimed to evaluate individual and interactive associations of multiscale risk factors for CVD outcomes including genetics and PSFs at middle and older-aged stages of the life course
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