Depressive mood is independently related to stroke and cardiovascular events in a community.

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.

Chronomic community screening reveals about 31% depression, elevated blood pressure and infradian vascular rhythm alteration.

Depression, which is a risk factor for cardiac morbidity and mortality, is not an unusual occurrence among individuals with coronary heart disease (CHD), but evidence concerning its role in the pathogenesis of this condition is less clear. Ambulatory blood pressure monitoring (ABPM) has become an important tool in the diagnosis and management of hypertension. Several previous studies have indicated that various kinds of target organ damage and cardiovascular morbidity are more strongly associated with a diagnosis by ABPM than through spot-checks in a clinical setting. This study investigated whether depressive mood was associated with changes in the about-weekly (circaseptan) and half-weekly (circasemiseptan) variations in blood pressure (BP) and heart rate (HR), including a BP surge on Mondays, in community-dwelling subjects monitored chronomically for the time structure (chronome) of their BP and HR variabilities. From April 2001 to April 2003, 217 subjects (85 men and 132 women; mean age: 56.8 +/- 11.3 yr) from U town, Hokkaido (latitude: 43.45 degrees N, longitude: 141.85 degrees E), self-monitored their BP and HR for 7 days starting around 11 a.m. on Thursday, and took readings at 30-minute intervals between 7 a.m. and 10 p.m., then at 60-minute intervals between 10 p.m. and 7 a.m. The data were retrieved and analyzed on a PC with appropriate commercial software (TM-2430-15; A&D Co., Japan). Subjects were asked about 15 items on a depression rating scale through a self-administered questionnaire. When the score amounted to 5 or higher, subjects were considered to be depressive. Student's t-test, a one-way analysis of variance (ANOVA), and cosinor methods with parametric tests were also used. A p-value below 0.05 was considered to indicate statistical significance (below 0.10: borderline statistical significance). Depression rating scales were obtained for 192 out of the 217 subjects enrolled in this study. Depression scores were (>) 5 in 72 subjects. The average values of systolic (S) and diastolic (D) BP were statistically significantly higher in depressed subjects (SBP: 129.2 vs 124.5 mmHg; p = 0.034; DBP: 79.0 vs 76.5 mmHg; p = 0.041). The 7-day average for HR did not differ between subjects with depression scores of < 5 or > 5. DBP dipping was less in the depressed subjects (16.30 vs 18.22%; p = 0.048). The dipping ratios of SBP and HR showed no statistically significant difference. In the group with depression scores of < 5, HR variability (estimated by the SD of HR and HR dip) was higher during vacations and lower on Mondays. The 24-h BP measures showed a novelty effect and a surge on Mondays. In the depressed group, a prominent circaseptan rhythm appeared to replace the novelty effect, vacation dip, and Monday surge. The results of this investigation indicate the clinical importance of the monitoring of depressed subjects. Fewer than 7 days of monitoring means a greater risk of false diagnosis, and thus a therapeutic decision including potentially unnecessary or inappropriate long-term treatment. Records shorter than 7 days would not have detected circaseptan BP dysrhythmia associated with a depressive state. Prominent circaseptans can provide new indications on the mechanisms underlying the strong relation between depression and adverse cardiac events. Future studies should aim at determining whether the treatment of depression, especially from the standpoint of a chronodiagnosis and chronotherapy, can reduce the incidence of adverse cardiac events, and whether this depends upon restoring normal BP and HR variability, i.e. anormal BP and HR chronome.

Impact of circadian amplitude and chronotherapy: relevance to prevention and treatment of stroke.

The long-acting calcium antagonist nifedipine reduces the incidence of stroke in Eastern Asia, as shown by the Shanghai Trial Of Nifedipine in the Elderly (STONE) and the Systolic Hypertension in China (Syst-China) trials. Recent trials in Japan have shown that benidipine may be more efficient than the former drug in preventing strokes in the elderly. Benidipine, commonly prescribed in Japan for a definite depressor effect, reportedly without causing remarkable fluctuations in blood pressure (BP), is investigated herein from a chronobiological viewpoint. Eighteen subjects (nine women and nine men, 39 to 87 years of age) with essential hypertension (office and ambulatory systolic, S/diastolic, D BP values above 160/95 mm Hg and 130/80 mm Hg, respectively) were enrolled in this investigation. Ambulatory BP was monitored at 30-min intervals for at least 24 h (ABPM-630, Colin Medical) before and after 4 weeks of crossover treatment with nifedipine tablets (twice daily, 20 mg/d) and benidipine (once daily, 4 mg/d, in the morning). The results indicate that: 1) benidipine and nifedipine reduce 24-h daytime (10:00-20:00) and nighttime (00:00-06:00) averages of SBP and DBP (P < 0.001); 2) the circadian double amplitude of BP is decreased after treatment with benidipine (from 28.6 to 21.1 mm Hg SBP and from 19.7 to 15.2 mm Hg DBP; P< 0.05), while the day-night difference in SBP is increased after treatment with nifedipine (18.6 vs 27.9 mm Hg, P< 0.01); and 3) the increase in the day-night difference of heart rate (HR) is significant after treatment with benidipine (13.6 vs 18.8 beats per minute, bpm; P< 0.05), but not with nifedipine. We have previously evaluated the usefulness of the circadian amplitude of BP as a prognostic tool of cardiovascular outcome, and found that an excessive circadian SBP or DBP amplitude was associated with an increased risk of vascular disease. The fact that benidipine reduces the circadian BP amplitude may be one reason for the superiority of this treatment over nifedipine in preventing an adverse outcome. A reduced heart rate variability (HRV) also predicts adverse cardiovascular outcomes in patients with overt cardiovascular disease and in hypertensive subjects. The fact that benidipine increases the day-night difference in HR may be another reason for the positive effects of this treatment.