Nocturnal blood pressure decline based on different time intervals and long-term cardiovascular risk: the Ohasama Study

<p>A diminished nocturnal decline in blood pressure (BP) represents a risk factor for cardiovascular disease. To define daytime and nighttime ambulatory BP, clock time-dependent methods are used when information on diary-based sleeping time is unavailable. We aimed to compare fixed-clock intervals with diary records to identify nocturnal BP declines as a predictor of long-term cardiovascular risk among the general population. Data were obtained from 1714 participants with no history of cardiovascular disease in Ohasama, Japan (mean age, 60.6 years; 64.9% women). We defined extreme dippers, dippers, non-dippers, and risers as nocturnal systolic BP decline ≥20%, 10–19%. 0–9%, and <0%, respectively. Over a mean follow-up period of 17.0 years, 206 cardiovascular deaths occurred. Based on diary records, multivariable-adjusted hazard ratios (HRs) for cardiovascular death compared with dippers were 1.24 (95% confidence interval [CI], 0.82–1.87) in extreme dippers, 1.21 (0.87–1.69) in non-dippers, and the highest HR of 2.31 (1.47–3.62) was observed in risers. Using a standard fixed-clock interval (daytime 09:00–21:00; nighttime 01:00–06:00), a nighttime 2 h-early shifted fixed-clock (daytime 09:00–21:00; nighttime 23:00–04:00), or a nighttime 2 h-late shifted fixed-clock (daytime 09:00–21:00; nighttime 03:00–08:00), the HR (95%CI) in risers compared with dippers was 1.57 (1.08–2.27), 2.02 (1.33–3.05), or 1.29 (0.86–1.92), respectively. Although use of diary records remains preferable, the standard and nighttime 2 h-early shifted fixed-clock intervals appear feasible for population-based studies.</p

Hazard ratios associated with masked hypertension (≥130/≥85 mm Hg) in participants with optimal, normal, and high-normal conventional blood pressure.

<p>Participants with optimal blood pressure without elevated HBP were the reference group. The categories of CBP were optimal (<120/<80 mm Hg), normal (120–129/80–84 mm Hg), and high-normal (130–139/85–89 mm Hg). When the systolic and diastolic blood pressures were in different categories, the participant was assigned to the higher category. Systolic/diastolic thresholds for hypertension on home measurement were ≥130/≥85 mm Hg. The HRs were adjusted for cohort as random effect and for sex, age, body mass index, smoking, total cholesterol, diabetes mellitus, and history of cardiovascular disease as fixed effects. Horizontal lines denote the 95% confidence interval. The diamond represents the pooled estimate in all participants with masked hypertension (MHT). The <i>p</i>-value for heterogeneity was derived by testing an ordinal variable in Cox proportional hazards regression coding for the three subgroups among participants with masked hypertension.</p

Kaplan-Meier survival function estimates by five categories of conventional blood pressure in 5,008 participants.

<p>(A) indicates risk for total mortality, and (B–D) indicate risks for cardiovascular events, stroke, and cardiac events, respectively. CBP categories were optimal (<120/<80 mm Hg), normal (120–129/80–84 mm Hg), high-normal (130–139/85–89 mm Hg), mild hypertension (140–159/90–99 mm Hg), and severe hypertension (≥160/≥100 mm Hg). When the systolic and diastolic blood pressures were in different categories, the participant was assigned to the higher category. The significance of the log-rank test for difference across the five categories was significant (<i>p</i><0.0001) for all of the end points.</p

Hazard ratios associated with masked hypertension (≥135/≥85 mm Hg) in participants with optimal, normal, and high-normal conventional blood pressure.

<p>Participants with optimal blood pressure without elevated HBP were the reference group. CBP categories were optimal (<120/<80 mm Hg), normal (120–129/80–84 mm Hg), and high-normal (130–139/85–89 mm Hg). When the systolic and diastolic blood pressures were in different categories, the participant was assigned to the higher category. Systolic/diastolic thresholds for hypertension on home measurement were ≥135/≥85 mm Hg. The HRs were adjusted for cohort as a random effect and for sex, age, body mass index, smoking, total cholesterol, diabetes mellitus, and history of cardiovascular disease as fixed effects. Horizontal lines denote the 95% confidence interval. The diamond represents the pooled estimate in all participants with masked hypertension (MHT). The <i>p</i>-value for heterogeneity was derived by testing an ordinal variable in Cox proportional hazards regression coding for the three subgroups among participants with masked hypertension.</p

Sensitivity analysis for total mortality and cardiovascular events with one cohort excluded.

<p>E/R indicates the number of cardiovascular events/participants at risk. Systolic/diastolic thresholds for CBP were as follows: optimal, <120/<80 mm Hg; normal, 120–129/80–84 mm Hg; high-normal, 130–139/85–89 mm Hg; mild hypertension, 140–159/90–99 mm Hg; and severe hypertension, ≥160/≥100 mm Hg. When the systolic and diastolic blood pressures were in different categories, the participant was assigned to the higher category. HRs reflect the risk for a 10-mm Hg increase in home systolic pressure and were adjusted for cohort as a random effect and for sex, age, body mass index, smoking, total cholesterol, diabetes mellitus, and history of cardiovascular disease as fixed effects. Significance of the HRs: *<i>p</i><0.05 and †<i>p</i><0.01.</p

Characteristics of participants with masked hypertension (home blood pressure ≥130/≥85 mm Hg) compared with participants with true optimal, normal, or high-normal blood pressure (home blood pressure <130/<85 mm Hg).

<p>Systolic/diastolic thresholds for CBP were as follows: optimal, <120/<80 mm Hg; normal, 120–129/80–84 mm Hg; and high-normal, 130–139/85–89 mm Hg. When the systolic and diastolic blood pressures were in different categories, the participant was assigned to the higher category. Significance of the difference from the adjacent lower category of CBP: *<i>p</i><0.05; †<i>p</i><0.01; ‡<i>p</i><0.001; and §<i>p</i><0.0001.</p

Sensitivity analysis for total mortality and cardiovascular events according to anthropometric characteristics and cardiovascular risk factors.

<p>E/R indicates the number of end points/participants at risk. White (race) included Finns, Greeks, and Uruguayans. Systolic/diastolic thresholds for CBP were as follows: optimal, <120/<80 mm Hg; normal, 120–129/80–84 mm Hg; high-normal, 130–139/85–89 mm Hg; mild hypertension, 140–159/90–99 mm Hg; and severe hypertension, ≥160/≥100 mm Hg. When the systolic and diastolic blood pressures were in different categories, the participant was assigned to the higher category. HRs reflect the risk for a 10-mm Hg increase in home systolic pressure and were adjusted for cohort as a random effect and for sex, age, body mass index, smoking, total cholesterol, diabetes mellitus, and history of cardiovascular disease as fixed effects. Significance of the HRs: *<i>p</i><0.05; †<i>p</i><0.01; and ‡<i>p</i><0.001.</p><p>§indicates a significant difference (<i>p</i>≤0.05) in the HRs between corresponding strata.</p

Standardized hazard ratios associated with diastolic home blood pressure by category of conventional blood pressure.

<p>Systolic/diastolic thresholds for CBP were as follows: optimal, <120/<80 mm Hg; normal, 120–129/80–84 mm Hg; high-normal, 130–139/85–89 mm Hg; mild hypertension, 140–159/90–99 mm Hg; and severe hypertension, ≥160/≥100 mm Hg. When the systolic and diastolic blood pressures were in different categories, the participant was assigned to the higher category. The category prehypertension includes participants with normal and high-normal blood pressure, and the category hypertension includes participants with mild and severe hypertension. The number of people at risk and the number of events are given in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001591#pmed-1001591-t003" target="_blank">Tables 3</a> and <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001591#pmed-1001591-t004" target="_blank">4</a>, respectively. HRs reflect the risk associated with a 5-mm Hg increase in home diastolic pressure. HRs were adjusted for cohort as a random effect and for sex, age, body mass index, smoking, total cholesterol, diabetes mellitus, and history of cardiovascular disease as fixed effects. Significance of the HRs: *<i>p</i><0.05; †<i>p</i><0.01; and ‡<i>p</i><0.001.</p

Incidence rates in 5,008 participants by increasing categories of conventional blood pressure.

<p>Rates (given as end points per 1,000 person-years) were standardized for sex and age by the direct method. CBP categories were optimal (<120/<80 mm Hg), normal (120–129/80–84 mm Hg), high-normal (130–139/85–89 mm Hg), mild hypertension (140–159/90–99 mm Hg), and severe hypertension (≥160/≥100 mm Hg). When the systolic and diastolic blood pressures were in different categories, the participant was assigned to the higher category. The number of end points contributing to the rates is presented. The <i>p</i>-values refer to the significance for linear trend across the five categories of CBP. HT, hypertension.</p

Characteristics of participants with masked hypertension (home blood pressure ≥135/≥85 mm Hg) compared with participants with true optimal, normal, or high-normal blood pressure (home blood pressure <135/<85 mm Hg).

<p>Systolic/diastolic thresholds for CBP were as follows: optimal, <120/<80 mm Hg; normal, 120–129/80–84 mm Hg; and high-normal, 130–139/85–89 mm Hg. When the systolic and diastolic blood pressures were in different categories, the participant was assigned to the higher category. Significance of the difference from the adjacent lower category of CBP: *<i>p</i><0.05; †<i>p</i><0.001; and ‡<i>p</i><0.0001.</p