Cardiovascular Disease: Depression and Telomere Length

描述（由申请人提供）：尽管抑郁症会增加心血管（CVD）事件的风险，与传统风险因素无关，但其潜在的病理生理机制尚不清楚。细胞衰老已被认为是CVD事件发展的一种新的假定机制。较短的白细胞端粒长度是细胞衰老的标志，与CVD的存在相关，也可能预测CVD事件。最近的证据表明，心理压力和抑郁症与较短的白细胞端粒长度有关，这表明细胞衰老可能是一种新的机制，可以解释抑郁症和CVD事件之间的关系。然而，这些风险标志物（抑郁和端粒长度）与CVD事件之间的确切关系仍然未知。对这些关系的研究对于理解抑郁症如何在细胞水平上促进年龄相关疾病（如CVD）的早期发作具有重要意义。具体目标：确定抑郁症、细胞衰老和CVD事件之间的关系，并进一步确定抑郁症和细胞衰老对CVD事件风险的独立贡献。 研究方法：10多年前进行了一项以人口为基础的前瞻性研究（1995年新斯科舍省健康调查，NSHS 95），参与者是从社会化医疗登记处随机挑选的，其中包括所有公民。在基线时获得传统的CVD风险因素。在基线时也获得了由流行病学研究中心抑郁量表评估的抑郁症状。从参与者中获得血沉棕黄层样品，并保存在-80 ℃冰箱中。参与者允许将他们的医疗登记记录与他们的调查数据相关联，以便可以检测到客观记录的先前和随后的CVD事件。我们建议分析血沉棕黄层样本的白细胞端粒长度，以确定抑郁症，端粒长度和10年的NSHS 95事件CVD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CVD风险因素，以及体重指数，炎症生物标志物（C-反应蛋白，白细胞介素-6和可溶性细胞间粘附分子-1），体力活动，其他医疗合并症，心血管药物的使用和抗抑郁药物的使用。这项研究将进一步了解抑郁症如何增加CVD事件的风险，并可能提出制定更有效的预防和治疗策略的方法。公共卫生相关性：抑郁症增加心血管疾病的风险。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，并可能提出制定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.