Yamanaka G, Otsuka K, Hotta N, Murakami S, Kubo Y, Matsuoka O, Takasugi E, Yamanaka T, Shinagawa M, Nunoda S, Nishimura Y, Shibata K, Saitoh H, Nishinaga M, Ishine M, Wada T, Okumiya K, Matsubayashi K, Yano S, Ishizuka S, Ichihara K, Cornélissen G, Halberg F
Department of Medicine, Tokyo Women's Medical University, Medical Center East, Nishiogu 2-1-10, Arakawa, Tokyo 116-8567, Japan.
Biomed Pharmacother. 2005 Oct;59 Suppl 1(Suppl 1):S31-9. doi: 10.1016/s0753-3322(05)80007-1.
By means of a multivariate Cox model, we investigated the predictive value of a depressive mood on vascular disease risk in middle-aged community-dwelling people. In 224 people (88 men and 136 women; mean age: 56.8 +/- 11.2 years) of U town, Hokkaido (latitude: 43.45 degrees N, longitude: 141.85 degrees E), a chronoecological health watch was started in April 2001. Consultations were repeated every 3 months. Results at the November 30, 2004 follow-up are presented herein. 7-day/24-h blood pressure (BP) and heart rate (HR) monitoring started on a Thursday, with readings taken at 30-min intervals between 07:00 h and 22:00 h and at 60-min intervals between 22:00 h and 07:00 h. Data stored in the memory of the monitor (TM-2430-15, A and D company, Japan) were retrieved and analyzed on a personal computer with a commercial software for this device. Subjects were asked to answer a self-administered questionnaire inquiring about 15 items of a depression scale, at the start of study and again after 1-2 years. Subjects with a score higher by at least two points at the second versus first screening were classified as having a depressive mood. The other subjects served as the control group. The mean follow-up time was 1064 days, during which four subjects suffered an adverse vascular outcome (myocardial infarction: one man and one woman; stroke: two men). Among the variables used in the Cox proportional hazard models, a depressive mood, assessed by the Geriatric Depression Scale (GDS), as well as the MESOR of diastolic (D) BP (DBP-MESOR) and the circadian amplitude of systolic (S) BP (SBP-Amplitude) showed a statistically significant association with the occurrence of adverse vascular outcomes. The GDS score during the second but not during the first session was statistically significantly associated with the adverse vascular outcome. In univariate analyses, the relative risk (RR) of developing outcomes was predicted by a three-point increase in the GDS scale (RR = 3.088, 95% CI: 1.375-6.935, P = 0.0063). Increases of 5 mmHg in DBP-MESOR and of 3 mmHg in SBP-Amplitude were associated with RRs of 2.143 (95% CI: 1.232-3.727, P = 0.0070) and 0.700 (95% CI: 0.495-0.989, P = 0.0430), respectively. In multivariate analyses, when both the second GDS score and the DBP-MESOR were used as continuous variables in the same model, GDS remained statistically significantly associated with the occurrence of cardiovascular death. After adjustment for DBP-MESOR, a three-point increase in GDS score was associated with a RR of 2.172 (95% CI: 1.123-4.200). Monday endpoints of the 7-day profile showed a statistically significant association with adverse vascular outcomes. A 5 mmHg increase in DBP on Monday was associated with a RR of 1.576 (95% CI: 1.011-2.457, P = 0.0446). The main result of the present study is that in middle-aged community-dwelling people, a depressive mood predicted the occurrence of vascular diseases beyond the prediction provided by age, gender, ABP, lifestyle and environmental conditions, as assessed by means of a multivariate Cox model. A depressive mood, especially enhanced for 1-2 years, was associated with adverse vascular outcomes. Results herein suggest the clinical importance of repetitive assessments of a depressive mood and the need to take sufficient care of depressed subjects. Another result herein is that circadian and circaseptan characteristics of BP variability measured 7-day/24-h predicted the occurrence of vascular disease beyond the prediction provided by age, gender, depressive mood and lifestyle, as assessed by means of a multivariate Cox model. Earlier, we showed that the morning surge in BP on Mondays was statistically significantly higher compared with other weekdays. Although a direct association between the Monday surge in BP and cardiovascular events could not be demonstrated herein, it is possible that the BP surge on Monday mornings may also trigger cardiovascular events. We have shown that depressive people exhibit a more prominent circaseptan variation in SBP, DBP and the double product (DP) compared to non-depressed subjects. In view of the strong relation between depression and adverse cardiac events, studies should be done to ascertain that depression is properly diagnosed and treated. Chronodiagnosis and chronotherapy can reduce an elevated blood pressure and improve the altered variability in BP and HR, thus reducing the incidence of adverse cardiac events. This recommendation stands at the basis of chronomics, focusing on prehabilitation in preference to rehabilitation, as a public service offered in several Japanese towns.
通过多变量Cox模型,我们研究了抑郁情绪对中年社区居民血管疾病风险的预测价值。在北海道U镇的224人(88名男性和136名女性;平均年龄:56.8±11.2岁,北纬43.45度,东经141.85度)中,于2001年4月开始了一项时间生态学健康监测。每3个月进行一次咨询。本文展示了2004年11月30日随访的结果。7天/24小时血压(BP)和心率(HR)监测于周四开始,在07:00至22:00之间每隔30分钟读取一次数据,在22:00至07:00之间每隔60分钟读取一次数据。存储在监测仪(TM - 2430 - 15,日本A和D公司)内存中的数据通过用于该设备的商业软件在个人电脑上进行检索和分析。在研究开始时以及1 - 2年后,要求受试者回答一份关于抑郁量表15项内容的自填问卷。在第二次筛查时得分比第一次至少高2分的受试者被归类为有抑郁情绪。其他受试者作为对照组。平均随访时间为1064天,在此期间有4名受试者出现不良血管结局(心肌梗死:1名男性和1名女性;中风:2名男性)。在Cox比例风险模型中使用的变量中,通过老年抑郁量表(GDS)评估的抑郁情绪,以及舒张压(D)BP的中值(DBP - MESOR)和收缩压(S)BP的昼夜振幅(SBP - Amplitude)与不良血管结局的发生显示出统计学上的显著关联。第二次而非第一次的GDS评分与不良血管结局在统计学上显著相关。在单变量分析中,GDS量表增加3分可预测发生结局的相对风险(RR)(RR = 3.088,95% CI:1.375 - 6.935,P = 0.0063)。DBP - MESOR增加5 mmHg和SBP - Amplitude增加3 mmHg分别与RR为2.143(95% CI:1.232 - 3.727,P = 0.0070)和0.700(95% CI:0.495 - 0.989,P = 0.0430)相关。在多变量分析中,当在同一模型中同时将第二次GDS评分和DBP - MESOR作为连续变量使用时,GDS与心血管死亡的发生仍在统计学上显著相关。在调整DBP - MESOR后,GDS评分增加3分与RR为2.172(95% CI:1.123 - 4.200)相关。7天记录的周一终点与不良血管结局显示出统计学上的显著关联。周一DBP增加5 mmHg与RR为1.576(95% CI:1.011 - 2.457,P = 0.0446)相关。本研究的主要结果是,在中年社区居民中,通过多变量Cox模型评估,抑郁情绪预测血管疾病的发生超出了年龄、性别、动态血压、生活方式和环境条件所提供的预测。抑郁情绪,尤其是持续1 - 2年加重的抑郁情绪,与不良血管结局相关。本文结果提示重复评估抑郁情绪的临床重要性以及对抑郁受试者给予充分关注的必要性。本文的另一个结果是,通过7天/24小时测量的血压变异性的昼夜和七日特征预测血管疾病的发生超出了年龄、性别、抑郁情绪和生活方式所提供的预测,这是通过多变量Cox模型评估的。此前,我们表明周一血压的早晨峰值与其他工作日相比在统计学上显著更高。尽管本文未能证明周一血压峰值与心血管事件之间的直接关联,但周一早晨的血压峰值也有可能引发心血管事件。我们已经表明,与非抑郁受试者相比,抑郁人群的收缩压、舒张压和双乘积(DP)表现出更显著的七日变化。鉴于抑郁与不良心脏事件之间的密切关系,应开展研究以确保抑郁得到正确诊断和治疗。时间诊断和时间治疗可以降低血压升高,并改善血压和心率的改变的变异性,从而降低不良心脏事件的发生率。这一建议是时间组学的基础,优先关注预康复而非康复,作为在日本几个城镇提供的一项公共服务。