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.
