Menniti Gabriella, Paquet Catherine, Han Hannah Yang, Dube Laurette, Nielsen Daiva E
School of Human Nutrition, McGill University, Montreal, QC, Canada.
Faculté des Sciences Administratives, Université Laval, Québec, QC, Canada.
Front Cardiovasc Med. 2021 Mar 16;8:599671. doi: 10.3389/fcvm.2021.599671. eCollection 2021.
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. Baseline data from the Canadian Longitudinal Study on Aging (CLSA; = 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). 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 PRSPSFs interactions were observed. 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.
心血管疾病（CVD）是一种复杂疾病，由多尺度风险因素导致，这些因素包括遗传、年龄以及诸如抑郁和社会孤立等心理社会因素（PSFs）。然而，以往的研究在将多尺度风险因素进行实际操作以确定生命历程中的个体关联和交互关联方面存在不足。因此，本研究旨在评估生命历程中中年和老年阶段心血管疾病结局的多尺度风险因素的个体关联和交互关联，包括遗传因素和心理社会因素。本调查使用了来自加拿大老龄化纵向研究（CLSA；9892例有全基因组基因分型数据）的基线数据。构建了一个包含39个单核苷酸多态性的心血管疾病多基因风险评分（PRS）。心理社会因素包括：（1）抑郁症状分为：“无”（第1组，参照组）、“当前存在”（第2组）、“目前无症状的临床抑郁症”（第3组）和“潜在的复发性抑郁症”（第4组）；（2）社会孤立指数作为一个二元变量，由婚姻状况、居住安排、退休状态、社交联系和社会参与组成。心脏相关疾病（HRD：心肌梗死、心绞痛和心脏病）是主要关注的结局，外周/血管相关疾病（PVRD：中风、外周血管疾病和高血压）是次要结局。针对社会人口学因素进行调整的多变量逻辑回归模型按年龄组（中年：45 - 69岁，老年：≥70岁）分层进行。在中年和老年参与者中，PRS与HRD相关[比值比（95%置信区间）]分别为[1.06（1.03 - 1.08），1.06（1.03 - 1.08）]。与参照组相比，大多数抑郁症状组与HRD和PVRD相关，但在老年人群中只有第4组与PVRD相关[1.69（1.08 - 2.64）]。社会孤立仅在中年人群中与PVRD相关[1.84（1.04 - 3.26）]；然而，在进行基因分型的队列中，社会孤立的CLSA参与者代表性不足（1.2%）。未观察到显著的PRS - PSFs交互作用。遗传因素和心理社会因素与心血管疾病独立相关。各年龄组的不同观察结果强调了推进对在特定时间点和生命历程中起作用的多尺度风险因素研究的必要性。未来的队列研究可能会受益于使用移动评估单元，以便更好地接触社会孤立的参与者以收集生物样本。
