Publications by authors named "Kei Asayama"

258 Publications

In-office and out-of-office blood pressure measurement.

J Hum Hypertens 2021 Mar 30. Epub 2021 Mar 30.

Tohoku Institute for Management of Blood Pressure, Sendai, Japan.

Accurate blood pressure measurement is the key procedure for the diagnosis and treatment of hypertension. In-office and out-of-office blood pressure measurements both have advantages and weak points, and multifaceted blood pressure information in individuals should be appropriately obtained and assessed. Validation of blood pressure measurement devices has long been an important issue, and several consortiums have emerged to try address it. Clinical guidelines should meet the demands of the region in which they are applied, and out-of-office measurements have been widely stated and recommended in the recently published guidelines worldwide. Appropriate assessment of blood pressure should be performed routinely in order to provide timely and accurate evidence regarding hypertension under any situation, including an unexpected pandemic.
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http://dx.doi.org/10.1038/s41371-021-00486-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008215PMC
March 2021

Lifetime risk of stroke stratified by chronic kidney disease and hypertension in the general Asian population: the Ohasama study.

Hypertens Res 2021 Mar 19. Epub 2021 Mar 19.

Tohoku Institute for Management of Blood Pressure, Sendai, Japan.

Lifetime risk (LTR) evaluates the absolute risk of developing a disease during the remainder of one's life. It can be a useful tool, enabling the general public to easily understand their risk of stroke. No study has been performed to determine the LTR of cardiovascular disease in patients with chronic kidney disease (CKD) with or without hypertension; therefore, we performed this study in an Asian population. We followed 1525 participants (66.0% women; age 63.1 years) in the general population of Ohasama, Japan. We defined CKD as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m and/or proteinuria. Hypertension was defined as a systolic/diastolic blood pressure ≥140/≥90 mmHg and/or the use of antihypertensive medication. We calculated the sex-specific LTR of stroke adjusted for the competing risk of death. During the mean follow-up period of 16.5 years, a first stroke occurred in 238 participants. The 10-year risk of stroke at the age of 45 years was 0.0% for men and women. The LTRs of stroke at the index age of 45 years (men/women) were 20.9%/14.5% for participants without CKD and hypertension, 34.1%/29.8% for those with CKD but not hypertension, 37.9%/27.3% for those with hypertension but not CKD, and 38.4%/36.4% for those with CKD and hypertension. The LTRs of stroke tended to be higher in younger participants than in older participants with CKD and/or hypertension. CKD contributed to the LTR of stroke, as did hypertension. The prevention of CKD and hypertension can reduce the LTR of stroke, especially in young populations.
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http://dx.doi.org/10.1038/s41440-021-00635-zDOI Listing
March 2021

Relative and Absolute Risk to Guide the Management of Pulse Pressure, an Age-Related Cardiovascular Risk Factor.

Am J Hypertens 2021 Mar 4. Epub 2021 Mar 4.

Laboratory of Neurosciences, Faculty of Medicine, University of Zulia, Maracaibo, Zulia, Venezuela.

Background: Pulse pressure (PP) reflects the age-related stiffening of the central arteries, but no study addressed the management of the PP-related risk over the human lifespan.

Methods: In 4663 young (18-49 years) and 7185 older adults (≥50 years), brachial PP was recorded over 24-hour. Total mortality and all major cardiovascular events combined (MACE) were co-primary endpoints. Cardiovascular death, coronary events and stroke were secondary endpoints.

Results: In young adults (median follow-up, 14.1 years; mean PP, 45.1 mmHg), greater PP was not associated with absolute risk; the endpoint rates were ≤2.01 per 1000 person-years. The adjusted hazard ratios expressed per 10mmHg PP increments were less than unity (P≤0.027) for MACE (0.67; 95% CI, 0.47-0.96) and cardiovascular death (0.33; 95% CI, 0.11-0.75). In older adults (median follow-up, 13.1 years; mean PP, 52.7 mmHg), the endpoint rates, expressing absolute risk, ranged from 22.5 to 45.4 per 1000 person-years and the adjusted hazard ratios, reflecting relative risk, from 1.09 to 1.54 (P<0.0001). The PPrelated relative risks of death, MACE and stroke decreased >3-fold from age 55 to 75 years, whereas absolute risk rose by a factor 3.

Conclusions: From 50 years onwards, the PP-related relative risk decreases, whereas absolute risk increases. From a lifecourse perspective, young adulthood provides a window of opportunity to manage risk factors and prevent target organ damage as forerunner of premature death and MACE. In older adults, treatment should address absolute risk, thereby extending life in years and quality.
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http://dx.doi.org/10.1093/ajh/hpab048DOI Listing
March 2021

Starting Antihypertensive Drug Treatment With Combination Therapy: Controversies in Hypertension - Con Side of the Argument.

Hypertension 2021 Mar 10;77(3):788-798. Epub 2021 Feb 10.

Research Institute Alliance for the Promotion of Preventive Medicine (APPREMED), Mechelen, Belgium (K.A., G.E.M., T.W.H., J.A.S).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.12858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884241PMC
March 2021

Ambulatory Blood Pressure Monitoring to Diagnose and Manage Hypertension.

Hypertension 2021 Feb 4;77(2):254-264. Epub 2021 Jan 4.

Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (K.A., Z.-Y.Z., L.T., J.A.S).

This review portrays how ambulatory blood pressure (BP) monitoring was established and recommended as the method of choice for the assessment of BP and for the rational use of antihypertensive drugs. To establish much-needed diagnostic ambulatory BP thresholds, initial statistical approaches evolved into longitudinal studies of patients and populations, which demonstrated that cardiovascular complications are more closely associated with 24-hour and nighttime BP than with office BP. Studies cross-classifying individuals based on ambulatory and office BP thresholds identified white-coat hypertension, an elevated office BP in the presence of ambulatory normotension as a low-risk condition, whereas its counterpart, masked hypertension, carries a hazard almost as high as ambulatory combined with office hypertension. What clinically matters most is the level of the 24-hour and the nighttime BP, while other BP indexes derived from 24-hour ambulatory BP recordings, on top of the 24-hour and nighttime BP level, add little to risk stratification or hypertension management. Ambulatory BP monitoring is cost-effective. Ambulatory and home BP monitoring are complimentary approaches. Their interchangeability provides great versatility in the clinical implementation of out-of-office BP measurement. We are still waiting for evidence from randomized clinical trials to prove that out-of-office BP monitoring is superior to office BP in adjusting antihypertensive drug treatment and in the prevention of cardiovascular complications. A starting research line, the development of a standardized validation protocol for wearable BP monitoring devices, might facilitate the clinical applicability of ambulatory BP monitoring.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803442PMC
February 2021

Antihypertensive drug effects according to the pretreatment self-measured home blood pressure: the HOMED-BP study.

BMJ Open 2020 12 12;10(12):e040524. Epub 2020 Dec 12.

Hygiene and Public Health, Teikyo University School of Medicine, Itabashi-ku, Japan.

Objectives: To clarify whether or not the antihypertensive drug effect is proportional to the baseline pretreatment self-measured home blood pressure (HBP) in accordance with the law of initial value (Wilder's law).

Design: A post-hoc analysis of a multicentre clinical trial.

Setting: Outpatients across Japan with mild-to-moderate essential hypertension.

Participants: Among 3518 randomised participants, 2423 who self-measured HBP during the pretreatment drug-free period (10-28 days after starting fixed-dose antihypertensive monotherapy) with a mean 7.0 years follow-up were eligible.

Main Outcome Measures: We analysed individual HBP readings during pretreatment and monotherapy.

Results: The day-to-day HBP during both the pretreatment period and monotherapy period remains almost the same throughout each period; the results were consistent, regardless of the pretreatment HBP. Following monotherapy, the reduction in the HBP increased by 2.2 mm Hg (95% CI: 1.8 to 2.5 mm Hg) per 10 mm Hg pretreatment HBP increase, up to 11.0 mm Hg (95% CI: 9.9 to 12.0 mm Hg) among patients with an HBP ≥165 mm Hg during pretreatment. Among the 1005 patients receiving low-dose monotherapy (defined daily dose: 0.5 units), the reduction peaked at 8.9-9.1 mm Hg in those with pretreatment HBP 155-164 mm Hg and ≥165 mm Hg (p=0.88).

Conclusions: According to Wilder's law, the HBP reduction due to fixed-dose monotherapy was proportional to the pretreatment HBP without any regression to the mean phenomenon. With low-dose antihypertensive drugs, however, the HBP reduction peaked in patients with a high pretreatment HBP, indicating the need for such patients to receive a sufficient amount of antihypertensive drug medication at the initial treatment.

Trial Registration: UMIN Clinical Trial Registry (http://www.umin.ac.jp/ctr), Unique identifier: C000000137.
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http://dx.doi.org/10.1136/bmjopen-2020-040524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735093PMC
December 2020

Association of Fatal and Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure.

Hypertension 2021 Jan 8;77(1):39-48. Epub 2020 Dec 8.

From the Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (J.D.M., W.-Y. Y, L.T., F.-F.W., J.A.S., Z.-Y.Z.).

Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and ≥96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (<0.001). Considering the 24-hour measurements, R statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.14929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7720872PMC
January 2021

Blood Pressure Phenotypes Defined by Ambulatory Blood Pressure Monitoring and Carotid Artery Changes in Community-Dwelling Older Japanese Adults: The Ohasama Study.

Tohoku J Exp Med 2020 11;252(3):269-279

Department of Hygiene and Public Health, Teikyo University School of Medicine.

White coat hypertension is defined as elevated blood pressure in the office, but a normal blood pressure out-of-office, whereas masked hypertension is defined as elevated blood pressure in the office, but normal out-of-office blood pressure. The objective was to investigate the associations between these blood pressure phenotypes and carotid artery changes. Conventional blood pressure, ambulatory blood pressure, and carotid ultrasonography were evaluated in 851 Ohasama residents (31.8% men; mean age 66.3 years). The blood pressure phenotypes were defined by the ordinary thresholds (140/90 mmHg for conventional blood pressure, 135/85 mmHg for daytime blood pressure) and then by the 2017 American College of Cardiology/American Heart Association (ACC/AHA) thresholds for hypertension (130/80 mmHg for both conventional and daytime blood pressure), irrespective of antihypertensive medication treatment status. Blood pressure phenotypes were linearly associated with the mean intima-media thickness of the carotid artery in ascending order for sustained normal blood pressure, white coat hypertension, masked hypertension, and sustained hypertension according to the ordinary thresholds and the 2017 ACC/AHA thresholds (both linear trends P < 0.0001) after adjustments for possible confounding factors. The odds ratios for the presence of carotid plaques showed similar linear trends with the blood pressure phenotypes according to the 2017 ACC/AHA thresholds (linear trend P < 0.0191). In conclusion, there was a close relationship between blood pressure phenotypes and carotid artery changes, suggesting that blood pressure phenotypes as defined by ambulatory blood pressure are potentially useful for risk stratification of carotid artery changes in the Japanese general population.
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http://dx.doi.org/10.1620/tjem.252.269DOI Listing
November 2020

Exercise Habits Are Associated with Improved Long-Term Mortality Risks in the Nationwide General Japanese Population: A 20-Year Follow-Up of the NIPPON DATA90 Study.

Tohoku J Exp Med 2020 11;252(3):253-262

Department of Public Health, Shiga University of Medical Science.

Exercise habits are known as a protective factor for a variety of diseases and thus recommended worldwide; however, few studies have examined long-term effects of exercise habits on mortality. We continuously monitored death status in a nationwide population sample of 7,709 eligible persons from the National Integrated Project for Prospective Observation of Noncommunicable Disease and its Trends in the Aged in 1990 (NIPPON DATA90), for which baseline data were obtained in 1990. To investigate the long-term impact of baseline exercise habits, we calculated the relative risk of non-exercisers (participants without regular voluntary exercise habits) in reference to exercisers (those with these habits) for all-cause or cause-specific mortality using a Cox proportional hazard model, in which the following confounding factors were appropriately adjusted: sex, age, body mass index, total energy intake, smoking, drinking, and history of cardiovascular disease. During a median 20 years of follow-up, 1,747 participants died, 99 of heart failure. The risk for all-cause mortality was 12% higher in non-exercisers than in exercisers (95% confidence interval, 1%-24%), which was also observed for mortality from heart failure, as 68% higher in non-exercisers than in exercises (95% confidence interval, 3%-173%). These associations were similarly observed when the participants were divided to subgroups by sex, age, and the light, moderate, or vigorous intensity of physical activity, without any significant heterogeneities (P > 0.1). The present study has revealed significant impact of exercise habits on long-term mortality risks, supporting worldwide recommendations for improvement of exercise habits.
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http://dx.doi.org/10.1620/tjem.252.253DOI Listing
November 2020

Blood Pressure and Chronic Kidney Disease Stratified by Gender and the Use of Antihypertensive Drugs.

J Am Heart Assoc 2020 08 14;9(16):e015592. Epub 2020 Aug 14.

Division of Public Health, Hygiene and Epidemiology Faculty of Medicine Tohoku Medical and Pharmaceutical University Sendai Japan.

Background The present study assessed the association between blood pressure (BP) and the risk of chronic kidney disease (CKD) according to gender and the use of antihypertensive drugs using data from a large-scale health checkup. Methods and Results We conducted a retrospective cohort study using the JMDC database, which contains annual health checkup data of Japanese employees and their dependents aged <75 years. We included 154 692 participants (men, 69.68%; mean age, 44.74 years) without CKD. CKD was indicated by an estimated glomerular filtration rate <60 mL/min per 1.73 m or the presence of proteinuria. During the mean follow-up period of 4.78 years, new-onset CKD occurred in 14 888 participants. When the normal BP group (systolic/diastolic BP <120/<80 mm Hg) without treatment was used as a reference, the hazard ratios of the high BP (130-139/80-89 mm Hg) and grade 1 (140-159/90-99 mm Hg) and grade 2 or 3 hypertension (≥160/≥100 mm Hg) groups were 1.11 (95% CI, 1.06-1.17), 1.36 (95% CI, 1.28-1.45), and 1.76 (95% CI, 1.56-1.99) for untreated men, respectively. However, in treated men, even normal BP was associated with a 1.5-fold higher risk of CKD. The association between BP and the risk of CKD was weaker in untreated women than in untreated men. The risk of CKD in treated women with normal BP was similar to that of untreated women with normal BP. Conclusions Gender differences were found in the association between BP and CKD risk. Kidney function in treated individuals should be followed carefully, especially in men.
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http://dx.doi.org/10.1161/JAHA.119.015592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7660816PMC
August 2020

Recent status of self-measured home blood pressure in the Japanese general population: a modern database on self-measured home blood pressure (MDAS).

Hypertens Res 2020 12 5;43(12):1403-1412. Epub 2020 Aug 5.

Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan.

Despite the clinical usefulness of self-measured home blood pressure (BP), reports on the characteristics of home BP have not been sufficient and have varied due to the measurement conditions in each study. We constructed a database on self-measured home BP, which included five Japanese general populations as subdivided aggregate data that were clustered and meta-analyzed according to sex, age category, and antihypertensive drug treatment at baseline (treated and untreated). The self-measured home BPs were collected after a few minutes of rest in a sitting position: (1) the morning home BP was measured within 1 h of waking, after urination, before breakfast, and before taking antihypertensive medication (if any); and (2) the evening home BP was measured just before going to bed. The pulse rate was simultaneously measured. Eligible data from 2000 onward were obtained. The morning BP was significantly higher in treated participants than in untreated people of the same age category, and the BP difference was more marked in women. Among untreated residents, home systolic/diastolic BPs measured in the morning were higher than those measured in the evening; the differences were 5.7/5.0 mmHg in women (ranges across the cohorts, 5.3-6.8/4.7-5.4 mmHg) and 7.3/7.7 mmHg in men (ranges, 6.4-8.5/7.0-8.7 mmHg). In contrast, the home pulse rate in women and men was 2.4 (range, 1.5-3.7) and 5.6 (range, 4.6-6.6) beats per minute, respectively, higher in the evening than in the morning. We demonstrated the current status of home BP and home pulse rate in relation to sex, age, and antihypertensive treatment status in the Japanese general population. The approach by which fine-clustered aggregate statistics were collected and integrated could address practical issues raised in epidemiological research settings.
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http://dx.doi.org/10.1038/s41440-020-0530-1DOI Listing
December 2020

Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19.

Hypertens Res 2020 10 31;43(10):1028-1046. Epub 2020 Jul 31.

Department of Endocrinology, Metabolism and Nephrology, Keio University School of Medicine, Tokyo, Japan.

Coronavirus disease-2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has affected more than seven million people worldwide, contributing to 0.4 million deaths as of June 2020. The fact that the virus uses angiotensin-converting enzyme (ACE)-2 as the cell entry receptor and that hypertension as well as cardiovascular disorders frequently coexist with COVID-19 have generated considerable discussion on the management of patients with hypertension. In addition, the COVID-19 pandemic necessitates the development of and adaptation to a "New Normal" lifestyle, which will have a profound impact not only on communicable diseases but also on noncommunicable diseases, including hypertension. Summarizing what is known and what requires further investigation in this field may help to address the challenges we face. In the present review, we critically evaluate the existing evidence for the epidemiological association between COVID-19 and hypertension. We also summarize the current knowledge regarding the pathophysiology of SARS-CoV-2 infection with an emphasis on ACE2, the cardiovascular system, and the kidney. Finally, we review evidence on the use of antihypertensive medication, namely, ACE inhibitors and angiotensin receptor blockers, in patients with COVID-19.
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http://dx.doi.org/10.1038/s41440-020-0515-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7393334PMC
October 2020

Comparison of nocturnal blood pressure based on home versus ambulatory blood pressure measurement: The Ohasama Study.

Clin Exp Hypertens 2020 Nov 11;42(8):685-691. Epub 2020 Jun 11.

Department of Hygiene and Public Health, Teikyo University School of Medicine , Tokyo, Japan.

Objectives: The nocturnal blood pressure (BP) is a strong predictor of hypertensive target organ damage including that in cardiovascular diseases. The use of ambulatory BP (ABP) monitoring has enabled the evaluation of nocturnal BP and detection of non-dippers. This study compared nocturnal BP values, nocturnal decline in BP, and the prevalence of non-dippers based on ABP and home BP (HBP) measurements in a general population.

Methods: Data on HBP measured with HEM 747-IC-N (Omron Healthcare Co., Ltd.) and 24-hour ABP measured with ABPM-630 (Nippon Colin) were obtained from fifty-five participants aged ≥ 20 years (mean age: 65.1 years, 78.2% women). To exclude a systematic difference between the two methods, we conducted a validation study for HBP and ABP in another population that consisted of hypertensive outpatients (mean age: 65.4 years, 53.4% women).

Results: After adjusting for the systematic difference in BP between the two methods calculated in the validation study (3.9 mmHg for systolic and 3.0 mmHg for diastolic), morning and daytime (average of morning and evening) HBP were significantly lower than morning (average of 2 h after waking) and daytime (average of being awake) ABP, respectively. No significant difference was found in nocturnal BP between HBP and ABP monitoring regardless of the quality of sleep during nocturnal HBP measurement. Agreement between HBP and ABP in the detection of non-dippers was low mainly due to the difference in daytime BP values. Conclusion: HBP monitoring may be a reliable alternative to ABP for the assessment of nocturnal BP.
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http://dx.doi.org/10.1080/10641963.2020.1779281DOI Listing
November 2020

A Combination of Blood Pressure and Total Cholesterol Increases the Lifetime Risk of Coronary Heart Disease Mortality: EPOCH-JAPAN.

J Atheroscler Thromb 2021 Jan 8;28(1):6-24. Epub 2020 Apr 8.

Department of Preventive Medicine and Public Health, School of Medicine, Keio University.

Aim: Lifetime risk (LTR) indicates the absolute risk of disease during the remainder of an individual's lifetime. We aimed to assess the LTRs for coronary heart disease (CHD) mortality associated with blood pressure (BP) and total cholesterol levels in an Asian population using a meta-analysis of individual participant data because no previous studies have assessed this risk.

Methods: We analyzed data from 105,432 Japanese participants in 13 cohorts. Apart from grade 1 and 2-3 hypertension groups, we defined "normal BP" as systolic/diastolic BP <130/<80 mmHg and "high BP" as 130-139/80-89 mmHg. The sex-specific LTR was estimated while considering the competing risk of death.

Results: During the mean follow-up period of 15 years (1,553,735 person-years), 889 CHD deaths were recorded. The 10-year risk of CHD mortality at index age 35 years was ≤ 0.11%, but the corresponding LTR was ≥ 1.84%. The LTR of CHD at index age 35 years steeply increased with an increase in BP of participants with high total cholesterol levels [≥ 5.7 mmol/L (220 mg/dL)]. This risk was 7.73%/5.77% (95% confidence interval: 3.53%-10.28%/3.83%-7.25%) in men/women with grade 2-3 hypertension and high total cholesterol levels. In normal and high BP groups, the absolute differences in LTRs between the low and high total cholesterol groups were ≤ 0.25% in men and ≤ 0.40% in women.

Conclusions: High total cholesterol levels contributed to an elevated LTR of CHD mortality in hypertensive individuals. These findings could help guide high-risk young individuals toward initiating lifestyle changes or treatments.
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http://dx.doi.org/10.5551/jat.52613DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7875142PMC
January 2021

Do estimated 24-h pulse pressure components affect outcome? The Ohasama study.

J Hypertens 2020 07;38(7):1286-1292

Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan.

Objective: Twenty-four-hour ambulatory pulse pressure (PP) is a powerful predictor of outcome. We attempted to apply the recently described PP components, an elastic (elPP), and systolic stiffening (stPP) components from 24-h ambulatory blood pressure (BP) monitoring (AMBP), and examine their influence on outcome in the Ohasama study population.

Design And Methods: Included were participants of the Ohasama study without history of cardiovascular disease (CVD), who were followed-up for total and CVD mortality, and for stroke morbidity. The PP components were derived from 24-h SBP and DBP using a model based on the nonlinear pressure--volume relationship in arteries expressing pressure stiffness relationship. Outcome predictive power was estimated by Cox regression models; hazard ratio with 95% confidence interval (CI), applied to elPP, and stPP, adjusted for age, sex, BMI, smoking, alcohol drinking, diabetes mellitus, total cholesterol, antihypertensive treatment, and mean arterial pressure (MAP), whenever appropriate.

Results: Of 1745 participants (age 61.4 ± 11.6, 65% women), 580 died, 212 of CVD, and 290 experienced a stroke during 17 follow-up years. PP was strongly correlated with elPP (r = 0.89) and less so with stPP (r = 0.58), and the correlation between the two components was weak (r = 0.15). After the adjustment, hazard ratio of PP per 1 SD increment for total mortality, CVD mortality, and stroke morbidity were 1.095 (95% CI 0.973-1.232), 1.207 (1.000-1.456), and 0.983 (0.829-1.166), respectively. Corresponding hazard ratios and 95% CIs were nonsignificant for elPP, and stPP. However, among participants with median pulse rate 68.5 bpm or less (median, n = 872), total (327 deaths) and CVD (131 deaths) mortality were predicted by elPP (per 1 SD increment), hazard ratio 1.231 (95% CI, 1.082-1.401), and 1.294 (95% CI, 1.069-1.566), respectively. In the subgroup of treated participants with hypertension and pulse rate 68.5 or less bpm (n = 309), total (177 deaths) and CVD (77 deaths) mortality were predicted by elPP, hazard ratio of 1.357 (95% CI, 1.131-1.628), and 1.417 (95% CI, 1.092-1.839), respectively. Stroke morbidity was not predicted by either PP or the PP components.

Conclusion: In a rural Japanese population, elPP but not stPP was predictive of total and CVD mortality even when adjusted for MAP and conventional risk factors in the subpopulation with slower pulse rate. This was mostly among the treated hypertensive patients.
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http://dx.doi.org/10.1097/HJH.0000000000002366DOI Listing
July 2020

Seasonal variation in blood pressure: Evidence, consensus and recommendations for clinical practice. Consensus statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability.

J Hypertens 2020 07;38(7):1235-1243

Department of Medicine and Surgery, University of Milano-Bicocca.

: Blood pressure (BP) exhibits seasonal variation with lower levels at higher environmental temperatures and higher at lower temperatures. This is a global phenomenon affecting both sexes, all age groups, normotensive individuals, and hypertensive patients. In treated hypertensive patients it may result in excessive BP decline in summer, or rise in winter, possibly deserving treatment modification. This Consensus Statement by the European Society of Hypertension Working Group on BP Monitoring and Cardiovascular Variability provides a review of the evidence on the seasonal BP variation regarding its epidemiology, pathophysiology, relevance, magnitude, and the findings using different measurement methods. Consensus recommendations are provided for health professionals on how to evaluate the seasonal BP changes in treated hypertensive patients and when treatment modification might be justified. (i) In treated hypertensive patients symptoms appearing with temperature rise and suggesting overtreatment must be investigated for possible excessive BP drop due to seasonal variation. On the other hand, a BP rise during cold weather, might be due to seasonal variation. (ii) The seasonal BP changes should be confirmed by repeated office measurements; preferably with home or ambulatory BP monitoring. Other reasons for BP change must be excluded. (iii) Similar issues might appear in people traveling from cold to hot places, or the reverse. (iv) BP levels below the recommended treatment goal should be considered for possible down-titration, particularly if there are symptoms suggesting overtreatment. SBP less than 110 mmHg requires consideration for treatment down-titration, even in asymptomatic patients. Further research is needed on the optimal management of the seasonal BP changes.
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http://dx.doi.org/10.1097/HJH.0000000000002341DOI Listing
July 2020

Day-to-day blood pressure variability is associated with lower cognitive performance among the Japanese community-dwelling oldest-old population: the SONIC study.

Hypertens Res 2020 05 19;43(5):404-411. Epub 2019 Dec 19.

Division of Health Science, Osaka University Graduate School of Medicine, Osaka, Japan.

Although high blood pressure (BP) and BP variability have been reported to be associated with cognitive impairment, few studies have investigated the association between home BP (HBP) and cognitive function in the oldest-old. The aim of this study was to evaluate whether the value of and the day-to-day variability in HBP was associated with cognitive function in a Japanese community-dwelling oldest-old population. Among 111 participants aged 85-87 years, cognitive function was assessed using the Japanese version of the Montreal Cognitive Assessment (MoCA-J). HBP was measured two times every morning for a median of 30 days. The value of and variability in HBP were calculated as the average and coefficient of variation (CV) of the measurements, respectively. The associations of HBP variability with MoCA-J were examined using multiple linear regression models. Of 111 participants, 47.7% were men, and 64.0% were taking medications for hypertension. The mean HBP was 141.9 ± 14.8/72.2 ± 8.4 mmHg, and the mean CV of HBP was 6.7 ± 1.9/6.8 ± 2.4. The mean total MoCA-J score was 22.9 ± 3.5. The MoCA-J score was significantly lower with increasing CVs of both systolic BP (b = -0.36, p = 0.034) and diastolic BP (b = -0.26, p = 0.046) after adjustment for possible confounding factors. The value of HBP was not associated with MoCA-J. In the community-dwelling oldest-old population, higher day-to-day HBP variability, but not the value of HBP, was associated with cognitive impairment. When measuring HBP, attention should be paid not only to the values but also to their variations.
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http://dx.doi.org/10.1038/s41440-019-0377-5DOI Listing
May 2020

N-Terminal Pro-B-Type Natriuretic Peptide Is a Predictor of Chronic Kidney Disease in an Asian General Population - The Ohasama Study.

Circ Rep 2019 Dec 11;2(1):24-32. Epub 2019 Dec 11.

Tohoku Institute for Management of Blood Pressure Sendai Japan.

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is known to increase in heart failure patients. Given that no reports have described the association between NT-proBNP and chronic kidney disease (CKD) incidence in Asian populations, we investigated this association in the Japanese population. We followed up 867 participants without CKD from the general population of Ohasama, Japan. We defined CKD as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m and/or proteinuria. In accordance with previous studies, the participants were classified into 4 groups according to NT-proBNP level (<30.0, 30.0-54.9, 55.0-124.9, and ≥125.0 pg/mL). The Cox model was applied to assess adjusted hazard ratios (HR) for CKD incidence after full adjustment including baseline eGFR. Participant mean age was 59.1 years, and 587 (67.7%) were women. During the mean follow-up period of 9.7 years, 177 participants developed CKD. When the group with NT-proBNP <30.0 pg/mL was used as the reference, adjusted HR for CKD incidence in the 30.0-54.9, 55.0-124.9, and ≥125.0 pg/mL groups were 1.34 (95% CI: 0.90-2.01), 1.25 (95% CI: 0.81-1.92), and 1.83 (95% CI: 1.05-3.18), respectively. NT-proBNP can be significantly predictive for CKD incidence in Asian populations.
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http://dx.doi.org/10.1253/circrep.CR-19-0044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7929707PMC
December 2019

Hyperuricemia predicts the risk for developing hypertension independent of alcohol drinking status in men and women: the Saku study.

Hypertens Res 2020 05 27;43(5):442-449. Epub 2019 Nov 27.

Department of Hygiene and Public Health, Teikyo University School of Medicine, Itabashi, Japan.

Hyperuricemia has been reported to be a risk factor for hypertension, but this association may be affected by alcohol consumption. This study aimed to investigate whether hyperuricemia remains a risk factor for hypertension after eliminating the effect of alcohol consumption. This study comprised 7848 participants (4247 men and 3601 women) aged 30-74 years without hypertension who had undergone a medical checkup between April 2008 and March 2009 at Saku Central Hospital, Nagano Prefecture, Japan. Hyperuricemia was defined as uric acid >7.0 mg/dl in men, ≥6.0 mg/dl in women, and/or receiving treatment for hyperuricemia or gout. The incidence of hypertension was defined as the first diagnoses of blood pressure ≥140/≥ 90 mmHg and/or initiations of antihypertensive drug treatment. Multivariable-adjusted hazard ratios (HRs) of hyperuricemia for the incidence of hypertension after adjustment for and classification by alcohol consumption were estimated using the Cox proportional hazard model. During a mean of 4.0 years of follow-up, 1679 individuals developed hypertension. After adjustment for alcohol consumption, the HRs (95% confidence interval) associated with hyperuricemia were 1.37 (1.19-1.58) in men and 1.54 (1.14-2.06) in women. Among nondrinkers, the HR was 1.29 (0.94-1.78) in men with hyperuricemia compared with men without, and the corresponding HR was 1.57 (1.11-2.22) in women. The corresponding HR was 1.88 (1.27-2.86) in all participants with baseline blood pressure <120/80 mmHg. The interactions between hyperuricemia and sex (P = 0.534) and between drinking and sex (P = 0.713) were not significant. In conclusion, hyperuricemia predicts the risk for developing hypertension independent of alcohol drinking status.
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http://dx.doi.org/10.1038/s41440-019-0361-0DOI Listing
May 2020

Opposing Age-Related Trends in Absolute and Relative Risk of Adverse Health Outcomes Associated With Out-of-Office Blood Pressure.

Hypertension 2019 12 21;74(6):1333-1342. Epub 2019 Oct 21.

First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, Kraków, Poland (K.S.-S., K.K.J.).

Participant-level meta-analyses assessed the age-specific relevance of office blood pressure to cardiovascular complications, but this information is lacking for out-of-office blood pressure. At baseline, daytime ambulatory (n=12 624) or home (n=5297) blood pressure were measured in 17 921 participants (51.3% women; mean age, 54.2 years) from 17 population cohorts. Subsequently, mortality and cardiovascular events were recorded. Using multivariable Cox regression, floating absolute risk was computed across 4 age bands (≤60, 61-70, 71-80, and >80 years). Over 236 491 person-years, 3855 people died and 2942 cardiovascular events occurred. From levels as low as 110/65 mm Hg, risk log-linearly increased with higher out-of-office systolic/diastolic blood pressure. From the youngest to the oldest age group, rates expressed per 1000 person-years increased (<0.001) from 4.4 (95% CI, 4.0-4.7) to 86.3 (76.1-96.5) for all-cause mortality and from 4.1 (3.9-4.6) to 59.8 (51.0-68.7) for cardiovascular events, whereas hazard ratios per 20-mm Hg increment in systolic out-of-office blood pressure decreased (≤0.0033) from 1.42 (1.19-1.69) to 1.09 (1.05-1.12) and from 1.70 (1.51-1.92) to 1.12 (1.07-1.17), respectively. These age-related trends were similar for out-of-office diastolic pressure and were generally consistent in both sexes and across ethnicities. In conclusion, adverse outcomes were directly associated with out-of-office blood pressure in adults. At young age, the absolute risk associated with out-of-office blood pressure was low, but relative risk high, whereas with advancing age relative risk decreased and absolute risk increased. These observations highlight the need of a lifecourse approach for the management of hypertension.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.12958DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6854319PMC
December 2019

Cardiovascular Events and Mortality in White Coat Hypertension.

Ann Intern Med 2019 10;171(8):602-603

University of Leuven, Leuven, Belgium (Z.Z., K.A., L.T., J.A.S.).

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http://dx.doi.org/10.7326/L19-0523DOI Listing
October 2019

Unattended Automated Measurements: Office and Out-of-Office Blood Pressures Affected by Medical Staff and Environment.

Hypertension 2019 12 7;74(6):1294-1296. Epub 2019 Oct 7.

From the Department of Hygiene and Public Health, Teikyo University School of Medicine, Tokyo, Japan (K.A., T.O.).

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13753DOI Listing
December 2019

Validation of an automated home blood pressure measurement device in oldest-old populations.

Hypertens Res 2020 01 18;43(1):30-35. Epub 2019 Sep 18.

Division of Health Science, Osaka University, Graduate School of Medicine, Osaka, Japan.

Despite the wide use of automated devices for the self-measurement of home blood pressure (BP), no evidence is available regarding the accuracy of such devices in oldest-old populations. The aim of this study was to validate the accuracy of the automated oscillometric upper arm-cuff BP-monitoring device according to an international protocol in oldest-old individuals. In 35 participants aged over 85 years old, BP was measured on the same arm sequentially using a mercury sphygmomanometer (by two observers) and an Omron HEM-7080IC. The difference between the test device and observer measurements and associated factors were evaluated according to the International Organization for Standardization (ISO) 81060-2:2013 protocol. A total of 105 pairs (three pairs per participant) of the test device and observer BP measurements were obtained. The mean (±standard deviation: SD) differences in systolic BP (SBP) and diastolic BP (DBP) between the methods were -0.7 ± 7.1 and -1.1 ± 4.5 mmHg, respectively, and those for each participant were -0.7 ± 5.8 mmHg for SBP and -1.1 ± 4.1 mmHg for DBP; the device therefore fulfilled the requirements of the ISO protocol. In the multivariate analysis with the linear mixed model, the difference was associated with the cuff size for SBP and pulse pressure for DBP. The Omron HEM-7080IC passed the ISO requirements for oldest-old individuals aged 85 years or older. This device can be recommended for clinical and self/home use in oldest-old populations.
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http://dx.doi.org/10.1038/s41440-019-0330-7DOI Listing
January 2020

Association of Office and Ambulatory Blood Pressure With Mortality and Cardiovascular Outcomes.

JAMA 2019 08;322(5):409-420

Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.

Importance: Blood pressure (BP) is a known risk factor for overall mortality and cardiovascular (CV)-specific fatal and nonfatal outcomes. It is uncertain which BP index is most strongly associated with these outcomes.

Objective: To evaluate the association of BP indexes with death and a composite CV event.

Design, Setting, And Participants: Longitudinal population-based cohort study of 11 135 adults from Europe, Asia, and South America with baseline observations collected from May 1988 to May 2010 (last follow-ups, August 2006-October 2016).

Exposures: Blood pressure measured by an observer or an automated office machine; measured for 24 hours, during the day or the night; and the dipping ratio (nighttime divided by daytime readings).

Main Outcomes And Measures: Multivariable-adjusted hazard ratios (HRs) expressed the risk of death or a CV event associated with BP increments of 20/10 mm Hg. Cardiovascular events included CV mortality combined with nonfatal coronary events, heart failure, and stroke. Improvement in model performance was assessed by the change in the area under the curve (AUC).

Results: Among 11 135 participants (median age, 54.7 years, 49.3% women), 2836 participants died (18.5 per 1000 person-years) and 2049 (13.4 per 1000 person-years) experienced a CV event over a median of 13.8 years of follow-up. Both end points were significantly associated with all single systolic BP indexes (P < .001). For nighttime systolic BP level, the HR for total mortality was 1.23 (95% CI, 1.17-1.28) and for CV events, 1.36 (95% CI, 1.30-1.43). For the 24-hour systolic BP level, the HR for total mortality was 1.22 (95% CI, 1.16-1.28) and for CV events, 1.45 (95% CI, 1.37-1.54). With adjustment for any of the other systolic BP indexes, the associations of nighttime and 24-hour systolic BP with the primary outcomes remained statistically significant (HRs ranging from 1.17 [95% CI, 1.10-1.25] to 1.87 [95% CI, 1.62-2.16]). Base models that included single systolic BP indexes yielded an AUC of 0.83 for mortality and 0.84 for the CV outcomes. Adding 24-hour or nighttime systolic BP to base models that included other BP indexes resulted in incremental improvements in the AUC of 0.0013 to 0.0027 for mortality and 0.0031 to 0.0075 for the composite CV outcome. Adding any systolic BP index to models already including nighttime or 24-hour systolic BP did not significantly improve model performance. These findings were consistent for diastolic BP.

Conclusions And Relevance: In this population-based cohort study, higher 24-hour and nighttime blood pressure measurements were significantly associated with greater risks of death and a composite CV outcome, even after adjusting for other office-based or ambulatory blood pressure measurements. Thus, 24-hour and nighttime blood pressure may be considered optimal measurements for estimating CV risk, although statistically, model improvement compared with other blood pressure indexes was small.
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http://dx.doi.org/10.1001/jama.2019.9811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6822661PMC
August 2019

Outcome-Driven Thresholds for Ambulatory Blood Pressure Based on the New American College of Cardiology/American Heart Association Classification of Hypertension.

Hypertension 2019 10 5;74(4):776-783. Epub 2019 Aug 5.

Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Belgium (L.T., Z.-Y.Z., W.-Y.Y., F.-F.W., C.-G.Y., J.A.S.).

The new American College of Cardiology/American Heart Association guideline reclassified office blood pressure and proposed thresholds for ambulatory blood pressure (ABP). We derived outcome-driven ABP thresholds corresponding with the new office blood pressure categories. We performed 24-hour ABP monitoring in 11 152 participants (48.9% women; mean age, 53.0 years) representative of 13 populations. We determined ABP thresholds resulting in multivariable-adjusted 10-year risks similar to those associated with elevated office blood pressure (120/80 mm Hg) and stages 1 and 2 of office hypertension (130/80 and 140/90 mm Hg). Over 13.9 years (median), 2728 (rate per 1000 person-years, 17.9) people died, 1033 (6.8) from cardiovascular disease; furthermore, 1988 (13.8), 893 (6.0), and 795 (5.4) cardiovascular and coronary events and strokes occurred. Using a composite cardiovascular end point, systolic/diastolic outcome-driven thresholds indicating elevated 24-hour, daytime, and nighttime ABP were 117.9/75.2, 121.4/79.6, and 105.3/66.2 mm Hg. For stages 1 and 2 ambulatory hypertension, thresholds were 123.3/75.2 and 128.7/80.7 mm Hg for 24-hour ABP, 128.5/79.6 and 135.6/87.1 mm Hg for daytime ABP, and 111.7/66.2 and 118.1/72.5 mm Hg for nighttime ABP. ABP thresholds derived from other end points were similar. After rounding, approximate thresholds for elevated 24-hour, daytime, and nighttime ABP were 120/75, 120/80, and 105/65 mm Hg, and for stages 1 and 2, ambulatory hypertension 125/75 and 130/80 mm Hg, 130/80 and 135/85 mm Hg, and 110/65 and 120/70 mm Hg. Outcome-driven ABP thresholds corresponding to elevated blood pressure and stages 1 and 2 of hypertension are similar to those proposed by the current American College of Cardiology/American Heart Association guideline.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.119.13512DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6739146PMC
October 2019

Fasting Blood Glucose Predicts Incidence of Hypertension Independent of HbA1c Levels and Insulin Resistance in Middle-Aged Japanese: The Saku Study.

Am J Hypertens 2019 11;32(12):1178-1185

Department of Hygiene and Public Health, Teikyo University School of Medicine, Itabashi, Japan.

Background: Relationships between blood glucose (BG) levels and insulin action, and incidence of hypertension have not been well known epidemiologically. This study aimed to investigate the association between indices of diabetes and the incidence of hypertension and compare the predictive powers of these indices in middle-aged Japanese.

Methods: This 5-year cohort study included 2,210 Japanese aged 30-64 years without hypertension. Hazard ratios of high fasting blood glucose (FBG) levels, high post-loaded BG levels, high glycated hemoglobin (HbA1c) levels, insulin resistance (defined by homeostasis model assessment of insulin resistance [HOMA-IR]) and impaired insulin secretion at baseline for the incidence of hypertension were estimated using multivariable-adjusted Cox proportional hazard models. Hypertension was defined as blood pressure ≥ 140/90 mm Hg or receiving antihypertensive treatment.

Results: During the follow-up, 456 participants developed hypertension. After adjustment for HbA1c and HOMA-IR, FBG was independently and significantly associated with hypertension. The hazard ratio of participants with FBG ≥ 7.0 mmol/l was 1.79 compared with those with FBG < 5.6 mmol/l. Even among those with HbA1c < 6.5%, HOMA-IR < 2.5, body mass index < 25 kg/m2, age < 55 years old, blood pressure < 130/80 mm Hg or non- and moderate drinking, the results were similar. High 120-minute BG level and impaired insulin secretion did not increase the risk for hypertension.

Conclusions: FBG was a predictable index for future incidence of hypertension in middle-aged Japanese men and women. This is the first study comparing predictive powers of indices of diabetes for the incidence of hypertension.
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http://dx.doi.org/10.1093/ajh/hpz123DOI Listing
November 2019

Age-Related Trends in Home Blood Pressure, Home Pulse Rate, and Day-to-Day Blood Pressure and Pulse Rate Variability Based on Longitudinal Cohort Data: The Ohasama Study.

J Am Heart Assoc 2019 08 23;8(15):e012121. Epub 2019 Jul 23.

Tohoku Institute for Management of Blood Pressure Sendai Japan.

Background Home blood pressure is a more accurate prognosticator than office blood pressure and allows the observation of day-to-day blood pressure variability. Information on blood pressure change during the life course links the prediction of blood pressure elevation with age. We prospectively assessed age-related trends in home blood pressure, home pulse rate, and their day-to-day variability evaluated as a coefficient of variation. Methods and Results We examined 1665 participants (men, 36.0%; mean age, 56.2 years) from the general population of Ohasama, Japan. A repeated-measures mixed linear model was used to estimate the age-related trends. In a mean of 15.9 years, we observed 5438 points of measurements including those at baseline. The home systolic blood pressure linearly increased with age and was higher in men than in women aged <70 years. There was an inverse-U-shaped age-related trend in home diastolic blood pressure. The day-to-day home systolic blood pressure linearly increased with age in individuals aged >40 years. However, an U-shaped age-related trend in day-to-day diastolic blood pressure variability with the nadir point at 65 to 69 years of age was observed. No significant sex differences in the day-to-day blood pressure variability were observed (P≥0.22). The average and day-to-day variability of home pulse rate decreased with age but were lower and higher, respectively, in men than in women. Conclusions The current descriptive data are needed to predict future home blood pressure and pulse rate. The data also provide information on the mechanism of day-to-day blood pressure and pulse rate variability.
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http://dx.doi.org/10.1161/JAHA.119.012121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6761623PMC
August 2019