Cardiovascular Disease: Depression and Telomere Length

描述(由申请人提供)：尽管抑郁症增加心血管(CVD)事件的风险，独立于传统的危险因素，但其潜在的病理生理机制尚不清楚。细胞衰老已被认为是心血管事件发生的一种新的可能机制。较短的白细胞端粒长度是细胞老化的标志，与心血管疾病的存在有关，也可能预测心血管疾病事件。最近的证据表明，心理应激和抑郁与较短的白细胞端粒长度有关，这表明细胞老化可能是解释抑郁与心血管事件之间关系的一种新机制。然而，这些风险标记物(抑郁和端粒长度)与心血管事件之间的确切关系仍不清楚。对这些关系的研究对于在细胞水平上理解抑郁症如何促进诸如心血管疾病等年龄相关疾病的更早发病具有重要的意义。具体目的：确定抑郁、细胞老化和心血管事件之间的关系，并二次确定抑郁和细胞老化对心血管事件风险的独立贡献。方法：一项基于人群的前瞻性研究(1995年新斯科舍省健康调查，NSHS95)在10多年前进行，参与者从社会化医疗登记中随机选择，包括所有公民。传统的心血管疾病危险因素是在基线时获得的。抑郁症状由流行病学研究中心抑郁量表评估，也在基线时获得。棕黄色的皮毛样本从参与者那里获得，并保存在零下80摄氏度的冰柜中。参与者允许将他们的医疗登记记录与他们的调查数据联系起来，这样就可以检测到客观记录的以前和之后的心血管事件。我们建议在NSHS95中检测黄褐色涂层样本的白细胞端粒长度，以确定抑郁、端粒长度和10年心血管事件之间的关系。我们还将确定这些关系是否独立于传统的心血管疾病危险因素，以及体重指数、炎症生物标志物(C-反应蛋白、白细胞介素6和可溶性细胞间黏附分子-1)、体力活动、其他医学并发症、心血管药物的使用和抗抑郁药物的使用。这项研究将加强对抑郁症如何增加发生心血管事件的风险的理解，并可能提出开发更有效的预防和治疗策略的方法。公共卫生相关性：抑郁症会增加心血管疾病的风险。造成这种关系的原因并不为人所知。这项研究将有助于确定为什么抑郁症会增加心血管疾病的风险，并可能提出开发更有效的预防和治疗策略的方法。

DESCRIPTION (provided by applicant): Although depression increases the risk of cardiovascular (CVD) events independent of traditional risk factors, the underlying pathophysiologic mechanisms are poorly understood. Cellular aging has been proposed as a novel putative mechanism in the development of CVD events. Shorter leukocyte telomere length, a marker of cellular aging, is associated with the presence of CVD, and may also predict CVD events. Recent evidence suggests that psychological stress and depression are associated with shorter leukocyte telomere length, suggesting that cellular aging may be a novel mechanism that explains the relation between depression and incident CVD events. However, the exact relations between these risk markers (depression and telomere length) and incident CVD events remain unknown. Investigation into these relations has important implications for understanding how, at the cellular level, depression may promote the earlier onset of age-related diseases such CVD. Specific Aims: To determine the relations among depression, cellular aging, and incident CVD events, and to secondarily determine the independent contributions of depression and cellular aging to the risk for incident CVD events. Methods: A population-based prospective study (1995 Nova Scotia Health Survey, NSHS95) was conducted over 10 years ago, in which participants were randomly selected from the socialized medical registry, which included all citizens. Traditional CVD risk factors were obtained at baseline. Depressive symptoms, assessed by the Center for Epidemiological Studies Depression scale, were also obtained at baseline. Buffy coat samples were obtained from participants and maintained in a -80 degree C freezer. Participants gave permission for their medical registry records to be linked to their survey data, so that objectively documented previous and subsequent CVD events could be detected. We propose to assay the buffy coat samples for leukocyte telomere length to determine the relations among depression, telomere length and 10-year incident CVD events in NSHS95. We will also determine whether these relations are independent of traditional CVD risk factors, and also body mass index, inflammatory biomarkers (C-reactive protein, interleukin-6, & soluble intercellular adhesion molecule-1), physical activity, other medical co-morbidities, use of cardiovascular medications, & antidepressant medication use. This study will provide enhanced understanding into how depression increases the risk of incident CVD events, and may suggest ways to develop more effective preventive and treatment strategies. PUBLIC HEALTH RELEVANCE: Depression increases the risk of cardiovascular disease. The reasons for this relation are not well known. This study will help determine why depression increases the risk of cardiovascular disease and may suggest ways to develop more effective preventive and treatment strategies.