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1.  Risk Stratification by Self-Measured Home Blood Pressure across Categories of Conventional Blood Pressure: A Participant-Level Meta-Analysis 
PLoS Medicine  2014;11(1):e1001591.
Jan Staessen and colleagues compare the risk of cardiovascular, cardiac, or cerebrovascular events in patients with elevated office blood pressure vs. self-measured home blood pressure.
Please see later in the article for the Editors' Summary
The Global Burden of Diseases Study 2010 reported that hypertension is worldwide the leading risk factor for cardiovascular disease, causing 9.4 million deaths annually. We examined to what extent self-measurement of home blood pressure (HBP) refines risk stratification across increasing categories of conventional blood pressure (CBP).
Methods and Findings
This meta-analysis included 5,008 individuals randomly recruited from five populations (56.6% women; mean age, 57.1 y). All were not treated with antihypertensive drugs. In multivariable analyses, hazard ratios (HRs) associated with 10-mm Hg increases in systolic HBP were computed across CBP categories, using the following systolic/diastolic CBP thresholds (in mm Hg): optimal, <120/<80; normal, 120–129/80–84; high-normal, 130–139/85–89; mild hypertension, 140–159/90–99; and severe hypertension, ≥160/≥100.
Over 8.3 y, 522 participants died, and 414, 225, and 194 had cardiovascular, cardiac, and cerebrovascular events, respectively. In participants with optimal or normal CBP, HRs for a composite cardiovascular end point associated with a 10-mm Hg higher systolic HBP were 1.28 (1.01–1.62) and 1.22 (1.00–1.49), respectively. At high-normal CBP and in mild hypertension, the HRs were 1.24 (1.03–1.49) and 1.20 (1.06–1.37), respectively, for all cardiovascular events and 1.33 (1.07–1.65) and 1.30 (1.09–1.56), respectively, for stroke. In severe hypertension, the HRs were not significant (p≥0.20). Among people with optimal, normal, and high-normal CBP, 67 (5.0%), 187 (18.4%), and 315 (30.3%), respectively, had masked hypertension (HBP≥130 mm Hg systolic or ≥85 mm Hg diastolic). Compared to true optimal CBP, masked hypertension was associated with a 2.3-fold (1.5–3.5) higher cardiovascular risk. A limitation was few data from low- and middle-income countries.
HBP substantially refines risk stratification at CBP levels assumed to carry no or only mildly increased risk, in particular in the presence of masked hypertension. Randomized trials could help determine the best use of CBP vs. HBP in guiding BP management. Our study identified a novel indication for HBP, which, in view of its low cost and the increased availability of electronic communication, might be globally applicable, even in remote areas or in low-resource settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Globally, hypertension (high blood pressure) is the leading risk factor for cardiovascular disease and is responsible for 9.4 million deaths annually from heart attacks, stroke, and other cardiovascular diseases. Hypertension, which rarely has any symptoms, is diagnosed by measuring blood pressure, the force that blood circulating in the body exerts on the inside of large blood vessels. Blood pressure is highest when the heart is pumping out blood (systolic blood pressure) and lowest when the heart is refilling (diastolic blood pressure). European guidelines define optimal blood pressure as a systolic blood pressure of less than 120 millimeters of mercury (mm Hg) and a diastolic blood pressure of less than 80 mm Hg (a blood pressure of less than 120/80 mm Hg). Normal blood pressure, high-normal blood pressure, and mild hypertension are defined as blood pressures in the ranges 120–129/80–84 mm Hg, 130–139/85–89 mm Hg, and 140–159/90–99 mm Hg, respectively. A blood pressure of more than 160 mm Hg systolic or 100 mm Hg diastolic indicates severe hypertension. Many factors affect blood pressure; overweight people and individuals who eat salty or fatty food are at high risk of developing hypertension. Lifestyle changes and/or antihypertensive drugs can be used to control hypertension.
Why Was This Study Done?
The current guidelines for the diagnosis and management of hypertension recommend risk stratification based on conventionally measured blood pressure (CBP, the average of two consecutive measurements made at a clinic). However, self-measured home blood pressure (HBP) more accurately predicts outcomes because multiple HBP readings are taken and because HBP measurement avoids the “white-coat effect”—some individuals have a raised blood pressure in a clinical setting but not at home. Could risk stratification across increasing categories of CBP be refined through the use of self-measured HBP, particularly at CBP levels assumed to be associated with no or only mildly increased risk? Here, the researchers undertake a participant-level meta-analysis (a study that uses statistical approaches to pool results from individual participants in several independent studies) to answer this question.
What Did the Researchers Do and Find?
The researchers included 5,008 individuals recruited from five populations and enrolled in the International Database of Home Blood Pressure in Relation to Cardiovascular Outcome (IDHOCO) in their meta-analysis. CBP readings were available for all the participants, who measured their HBP using an oscillometric device (an electronic device for measuring blood pressure). The researchers used information on fatal and nonfatal cardiovascular, cardiac, and cerebrovascular (stroke) events to calculate the hazard ratios (HRs, indicators of increased risk) associated with a 10-mm Hg increase in systolic HBP across standard CBP categories. In participants with optimal CBP, an increase in systolic HBP of 10-mm Hg increased the risk of any cardiovascular event by nearly 30% (an HR of 1.28). Similar HRs were associated with a 10-mm Hg increase in systolic HBP for all cardiovascular events among people with normal and high-normal CBP and with mild hypertension, but for people with severe hypertension, systolic HBP did not significantly add to the prediction of any end point. Among people with optimal, normal, and high-normal CBP, 5%, 18.4%, and 30.4%, respectively, had a HBP of 130/85 or higher (“masked hypertension,” a higher blood pressure in daily life than in a clinical setting). Finally, compared to individuals with optimal CBP without masked hypertension, individuals with masked hypertension had more than double the risk of cardiovascular disease.
What Do These Findings Mean?
These findings indicate that HBP measurements, particularly in individuals with masked hypertension, refine risk stratification at CBP levels assumed to be associated with no or mildly elevated risk of cardiovascular disease. That is, HBP measurements can improve the prediction of cardiovascular complications or death among individuals with optimal, normal, and high-normal CBP but not among individuals with severe hypertension. Clinical trials are needed to test whether the identification and treatment of masked hypertension leads to a reduction of cardiovascular complications and is cost-effective compared to the current standard of care, which does not include HBP measurements and does not treat people with normal or high-normal CBP. Until then, these findings provide support for including HBP monitoring in primary prevention strategies for cardiovascular disease among individuals at risk for masked hypertension (for example, people with diabetes), and for carrying out HBP monitoring in people with a normal CBP but unexplained signs of hypertensive target organ damage.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Mark Caulfield
The US National Heart, Lung, and Blood Institute has patient information about high blood pressure (in English and Spanish) and a guide to lowering high blood pressure that includes personal stories
The American Heart Association provides information on high blood pressure and on cardiovascular diseases (in several languages); it also provides personal stories about dealing with high blood pressure
The UK National Health Service Choices website provides detailed information for patients about hypertension (including a personal story) and about cardiovascular disease
The World Health Organization provides information on cardiovascular disease and controlling blood pressure; its A Global Brief on Hypertension was published on World Health Day 2013
The UK charity Blood Pressure UK provides information about white-coat hypertension and about home blood pressure monitoring
MedlinePlus provides links to further information about high blood pressure, heart disease, and stroke (in English and Spanish)
PMCID: PMC3897370  PMID: 24465187
2.  The confounding effect of cryptic relatedness for environmental risks of systolic blood pressure on cohort studies 
The impact of cryptic relatedness (CR) on genomic association studies is well studied and known to inflate false-positive rates as reported by several groups. In contrast, conventional epidemiological studies for environmental risks, the confounding effect of CR is still uninvestigated. In this study, we investigated the confounding effect of unadjusted CR among a rural cohort in the relationship between environmental risk factors (body mass index, smoking status, alcohol consumption) and systolic blood pressure. We applied the methods of population-based whole-genome association studies for the analysis of the genome-wide single nucleotide polymorphism data in 1622 subjects, and detected 20.2% CR in this cohort population. In the case of the sample size, approximately 1000, the ratio of CR to the population was 20.2%, the population prevalence 25%, the prevalence in the CR 26%, heritability for liability 14.3% and prevalence in the subpopulation without CR 26%, the difference of estimated regression coefficient between samples with and without CR was not significant (P-value = 0.55). On the other hand, in another case with approximately >20% heritability for liability, we showed that confounding due to CR biased the estimation of exposure effects.
PMCID: PMC3893157  PMID: 24498600
confounding effect; cryptic relatedness; systolic blood pressure
3.  Outcome-Driven Thresholds for Home Blood Pressure Measurement 
Hypertension  2012;61(1):27-34.
The lack of outcome-driven operational thresholds limits the clinical application of home blood pressure (BP) measurement. Our objective was to determine an outcome-driven reference frame for home BP measurement. We measured home and clinic BP in 6470 participants (mean age, 59.3 years; 56.9% women; 22.4% on antihypertensive treatment) recruited in Ohasama, Japan (n=2520); Montevideo, Uruguay (n=399); Tsurugaya, Japan (n=811); Didima, Greece (n=665); and nationwide in Finland (n=2075). In multivariable-adjusted analyses of individual subject data, we determined home BP thresholds, which yielded 10-year cardiovascular risks similar to those associated with stages 1 (120/80 mm Hg) and 2 (130/85 mm Hg) prehypertension, and stages 1 (140/90 mm Hg) and 2 (160/100 mm Hg) hypertension on clinic measurement. During 8.3 years of follow-up (median), 716 cardiovascular end points, 294 cardiovascular deaths, 393 strokes, and 336 cardiac events occurred in the whole cohort; in untreated participants these numbers were 414, 158, 225, and 194, respectively. In the whole cohort, outcome-driven systolic/diastolic thresholds for the home BP corresponding with stages 1 and 2 prehypertension and stages 1 and 2 hypertension were 121.4/77.7, 127.4/79.9, 133.4/82.2, and 145.4/86.8 mm Hg; in 5018 untreated participants, these thresholds were 118.5/76.9, 125.2/79.7, 131.9/82.4, and 145.3/87.9 mm Hg, respectively. Rounded thresholds for stages 1 and 2 prehypertension and stages 1 and 2 hypertension amounted to 120/75, 125/80, 130/85, and 145/90 mm Hg, respectively. Population-based outcome-driven thresholds for home BP are slightly lower than those currently proposed in hypertension guidelines. Our current findings could inform guidelines and help clinicians in diagnosing and managing patients.
PMCID: PMC3607331  PMID: 23129700
home blood pressure measurement; blood pressure; hypertension; epidemiology; thresholds
4.  The International Database of HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO): moving from baseline characteristics to research perspectives 
The objective of this study is to construct an International Database of HOme blood pressure in relation to Cardiovascular Outcome (IDHOCO). The main goal of this database is to determine outcome-based diagnostic thresholds for the self-measured home blood pressure (BP). Secondary objectives include investigating the predictive value of white-coat and masked hypertension, morning and evening BP, BP and heart rate variability, and the home arterial stiffness index. We also aim to determine an optimal schedule for home BP measurements that provides the most accurate risk stratification. Eligible studies are population-based, have fatal as well as nonfatal outcomes available for analysis, comply with ethical standards, and have been previously published in peer-reviewed journals. In a meta-analysis based on individual subject data, composite and cause-specific cardiovascular events will be related to various indexes derived by home BP measurement. The analyses will be stratified by a cohort and adjusted for the clinic BP and established cardiovascular risk factors. The database includes 6753 subjects from five cohorts recruited in Ohasama, Japan (n = 2777); Finland (n = 2075); Tsurugaya, Japan (n = 836); Didima, Greece (n = 665); and Montevideo, Uruguay (n = 400). In these five cohorts, during a total of 62 106 person-years of follow-up (mean 9.2 years), 852 subjects died and 740 participants experienced a fatal or nonfatal cardiovascular event. IDHOCO provides a unique opportunity to investigate several hypotheses that could not reliably be studied in individual studies. The results of these analyses should be of help to clinicians involved in the management of patients with suspected or established hypertension.
PMCID: PMC3606707  PMID: 22763485
BP measurement; epidemiology; home; self-measurement
5.  Cancer patients on Twitter: a novel patient community on social media 
BMC Research Notes  2012;5:699.
Patients increasingly turn to the Internet for information on medical conditions, including clinical news and treatment options. In recent years, an online patient community has arisen alongside the rapidly expanding world of social media, or “Web 2.0.” Twitter provides real-time dissemination of news, information, personal accounts and other details via a highly interactive form of social media, and has become an important online tool for patients. This medium is now considered to play an important role in the modern social community of online, “wired” cancer patients.
Fifty-one highly influential “power accounts” belonging to cancer patients were extracted from a dataset of 731 Twitter accounts with cancer terminology in their profiles. In accordance with previously established methodology, “power accounts” were defined as those Twitter accounts with 500 or more followers. We extracted data on the cancer patient (female) with the most followers to study the specific relationships that existed between the user and her followers, and found that the majority of the examined tweets focused on greetings, treatment discussions, and other instances of psychological support. These findings went against our hypothesis that cancer patients’ tweets would be centered on the dissemination of medical information and similar “newsy” details.
At present, there exists a rapidly evolving network of cancer patients engaged in information exchange via Twitter. This network is valuable in the sharing of psychological support among the cancer community.
PMCID: PMC3599295  PMID: 23270426
Breast cancer; Breast neoplasms; Internet; Leukemia; Social media; Twitter messaging; Web 2.0
6.  A Metabolomic Approach to Clarifying the Effect of AST-120 on 5/6 Nephrectomized Rats by Capillary Electrophoresis with Mass Spectrometry (CE-MS) 
Toxins  2012;4(11):1309-1322.
The oral adsorbent AST-120 is composed of spherical carbon particles and has an adsorption ability for certain small-molecular-weight compounds that accumulate in patients with chronic kidney disease (CKD). So far, very few compounds are known to be adsorbed by AST-120 in vivo. To examine the effect of AST-120 in vivo, we comprehensively evaluated the plasma concentrations of 146 compounds (61 anions and 85 cations) in CKD model rats, with or without four weeks of treatment with AST-120. By capillary electrophoresis with mass spectrometry, we identified 6 anions and 17 cations that were significantly decreased by AST-120 treatment. In contrast, we also identified 2 cations that were significantly increased by AST-120. Among them, 4 anions, apart from indoxyl sulfate and hippurate, and 19 cations were newly identified in this study. The plasma levels of N-acetyl-neuraminate, 4-pyridoxate, 4-oxopentanoate, glycine, γ-guanidinobutyrate, N-γ-ethylglutamine, allantoin, cytosine, 5-methylcytosine and imidazole-4-acetate were significantly increased in the CKD model compared with the sham-operated group, and were significantly decreased by AST-120 treatment. Therefore, these 10 compounds could be added as uremic compounds that indicate the effect of AST-120 treatment. This study provides useful information not only for identifying the indicators of AST-120, but also for clarifying changes in the metabolic profile by AST-120 treatment in the clinical setting.
PMCID: PMC3509710  PMID: 23202318
AST-120; uremic toxin; CE-MS
7.  Impact of Blunted Perception of Dyspnea on Medical Care Use and Expenditure, and Mortality in Elderly People 
Dyspnea is an alarming symptom responsible for millions of patient visits each year. Poor perception of dyspnea might be reasonably attributed to an inappropriately low level of fear and inadequate earlier medical treatment for both patients and physicians, resulting in subsequent intensive care. This study was conducted to evaluate medical care use and cost, and mortality according to the perception of dyspnea in community-dwelling elderly people. We analyzed baseline data from a community-based Comprehensive Geriatric Assessment in 2002. The perception of dyspnea in 479 Japanese community-dwelling elderly people with normal lung function was measured in August 2002. The sensation of dyspnea during breathing with a linear inspiratory resistance of 10, 20, and 30 cmH2O/L/s was rated using the Borg scale. According to the perception of dyspnea, we divided the elderly into tertiles and compared all hospitalizations, out-patient visits, costs, and death through computerized linkage with National Health Insurance beneficiaries claims history files between August 2002 and March 2008. In-patient hospitalization days and medical care costs significantly increased with the blunted perception of dyspnea, resulting in an increase in total medical-costs with blunted perception of dyspnea. With low perception group as reference, the hazard ratios of all-cause mortality were 0.65 (95% CI 0.23–1.89) for intermediate perception group and 0.31 (0.10–0.97) for high perception group, indicating the mortality rate also significantly increased with the blunted perception of dyspnea after multivariates adjustment (p = 0.04). The blunted perception of dyspnea is related to hospitalization, large medical costs, and all-cause mortality in community-dwelling elderly people. These findings provide a rational for preventing serious illness with careful monitoring of objective conditions in the elderly.
PMCID: PMC3389490  PMID: 22783203
dyspnea; the elderly; medical cost; medical service use; mortality
8.  Impact of obesity, overweight and underweight on life expectancy and lifetime medical expenditures: the Ohsaki Cohort Study 
BMJ Open  2012;2(3):e000940.
People who are obese have higher demands for medical care than those of the normal weight people. However, in view of their shorter life expectancy, it is unclear whether obese people have higher lifetime medical expenditure. We examined the association between body mass index, life expectancy and lifetime medical expenditure.
Prospective cohort study using individual data from the Ohsaki Cohort Study.
Miyagi Prefecture, northeastern Japan.
The 41 965 participants aged 40–79 years.
Primary and secondary outcome measures
The life expectancy and lifetime medical expenditure aged from 40 years.
In spite of their shorter life expectancy, obese participants might require higher medical expenditure than normal weight participants. In men aged 40 years, multiadjusted life expectancy for those who were obese participants was 41.4 years (95% CI 38.28 to 44.70), which was 1.7 years non-significantly shorter than that for normal weight participants (p=0.3184). Multiadjusted lifetime medical expenditure for obese participants was £112 858.9 (94 954.1–131 840.9), being 14.7% non-significantly higher than that for normal weight participants (p=0.1141). In women aged 40 years, multiadjusted life expectancy for those who were obese participants was 49.2 years (46.14–52.59), which was 3.1 years non-significantly shorter than for normal weight participants (p=0.0724), and multiadjusted lifetime medical expenditure was £137 765.9 (123 672.9–152 970.2), being 21.6% significantly higher (p=0.0005).
According to the point estimate, lifetime medical expenditure might appear to be higher for obese participants, despite their short life expectancy. With weight control, more people would enjoy their longevity with lower demands for medical care.
Article summary
Article focus
Obese people have higher needs and demands for medical care.
Obesity is associated with an increased risk of mortality.
In view of the decreased life expectancy in obese participants, it is unclear whether lifetime medical expenditure increases or decreases as a result.
Key messages
In spite of their short life expectancy, obese men and women had approximately 14.7% and 21.6% higher lifetime medical expenditure in comparison with normal weight participants, respectively.
With better weight control, more people would enjoy their longevity with lower needs and demands for medical care.
Strengths and limitations of this study
This is the first study to have investigated the association between body mass index, life expectancy and lifetime medical expenditure calculated from individual medical expenditure and mortality data over a long period in a general population.
There was a limit to the accurate estimation of life expectancy and lifetime medical expenditure for obese participants because the Japanese population has a low prevalence of body mass index≥30.0 kg/m2.
PMCID: PMC3353127  PMID: 22581797
9.  Gamma-Glutamyltransferase and Cancer Incidence: The Ohsaki Cohort Study 
Journal of Epidemiology  2012;22(2):144-150.
Although experimental studies have shown that gamma-glutamyltransferase (GGT) has a role in tumor progression, epidemiologic evidence for a relationship between GGT and cancer incidence is limited. The present study investigated the association between GGT and cancer incidence and assessed the role of alcohol consumption in this association.
We examined a cohort of 15 031 Japanese adults aged 40 to 79 years who attended a health checkup in 1995 and were free of cancer at that time. GGT was measured using the Szasz method. The participants were then followed from 1 January 1996 until 31 December 2005, and cancer incidence was recorded by using the Miyagi Regional Cancer Registry. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed for each quartile of GGT and compared. The lowest quartile (GGT <13.0 IU/ml) was used as the reference category.
We documented 1505 cancers. Among participants in the highest quartile (GGT ≥31.0 IU/ml), the multivariate HR for any cancer was 1.28 (95% CI, 1.08–1.53; P for trend, <0.001), the HR for colorectal cancer was significantly greater than unity, and the HRs for esophageal, pancreatic, and breast cancers were greater than unity but not significantly so. This positive trend was observed only in current drinkers.
Our findings suggest that there is a positive relationship between GGT and cancer incidence only for alcohol-related cancers in current drinkers and that the positive association of GGT with cancer incidence largely reflects alcohol consumption.
PMCID: PMC3798593  PMID: 22277791
gamma-glutamyltransferase; cancer incidence; population-based; prospective study; Ohsaki Study
10.  Green tea consumption and the risk of incident functional disability in elderly Japanese: the Ohsaki Cohort 2006 Study123 
Background: Previous studies have reported that green tea consumption is associated with a lower risk of diseases that cause functional disability, such as stroke, cognitive impairment, and osteoporosis. Although it is expected that green tea consumption would lower the risk of incident functional disability, this has never been investigated directly.
Objective: The objective was to determine the association between green tea consumption and incident functional disability in elderly individuals.
Design: We conducted a prospective cohort study in 13,988 Japanese individuals aged ≥65 y. Information on daily green tea consumption and other lifestyle factors was collected via questionnaire in 2006. Data on functional disability were retrieved from the public Long-term Care Insurance database, in which subjects were followed up for 3 y. We used Cox proportional hazards regression analysis to investigate the association between green tea consumption and functional disability.
Results: The 3-y incidence of functional disability was 9.4% (1316 cases). The multiple-adjusted HR (95% CI) of incident functional disability was 0.90 (0.77, 1.06) among respondents who consumed 1–2 cups green tea/d, 0.75 (0.64, 0.88) for those who consumed 3–4 cups/d, and 0.67 (0.57, 0.79) for those who consumed ≥5 cups/d in comparison with those who consumed <1 cup/d (P-trend < 0.001).
Conclusion: Green tea consumption is significantly associated with a lower risk of incident functional disability, even after adjustment for possible confounding factors.
PMCID: PMC3278248  PMID: 22277550
11.  Randomized controlled trial for an effect of catechin-enriched green tea consumption on adiponectin and cardiovascular disease risk factors 
Food & Nutrition Research  2011;55:10.3402/fnr.v55i0.8326.
Previous observational studies have indicated that green tea (GT) consumption is associated with reduced mortality from cerebral infarction but not with mortality from cerebral hemorrhage. Therefore, we hypothesized that GT exerts a direct antiatherosclerotic effect without any effect on hypertension. To investigate this hypothesis, we focused on adiponectin that seems to be among the several key players in atherosclerosis.
The objective of this randomized controlled trial (RCT) was to assess whether the consumption of catechin-enriched GT affects serum adiponectin levels and cardiovascular disease (CVD) risk factors among apparently healthy subjects.
A total of 51 individuals participated in the study. Eligible participants were randomly assigned into GT consumption groups with either high catechin (400 mg/day) or low catechin (100 mg/day). The study participants were asked to stop GT consumption for 2 weeks (washout period), following which they were to start drinking the provided GT beverages everyday for 9 weeks. The outcome measures were changes in the adiponectin levels and CVD risk factors (body weight, body mass index, waist circumference, blood pressure, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, fasting plasma glucose, as well as aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase, uric acid, and high-sensitive C-reactive protein).
After intervention for 9 weeks, we found no significant difference between the high- and low catechin group with respect to changes in the serum adiponectin level: 0.35 µg/ml (95% confidence interval (CI): −1.03, 1.74). Also, no significant difference was observed between the high- and low catechin groups with respect to changes in any of the measured CVD risk factors.
This RCT showed no significant difference between the high- and low catechin groups with respect to changes in the serum adiponectin level and any CVD risk factors.
PMCID: PMC3229814  PMID: 22144918
randomized controlled trial; green tea; catechin; adiponectin; cardiovascular disease risk factors
12.  Impact of walking on life expectancy and lifetime medical expenditure: the Ohsaki Cohort Study 
BMJ Open  2011;1(2):e000240.
People who spend a longer time walking have lower demands for medical care. However, in view of their longer life expectancy, it is unclear whether their lifetime medical expenditure increases or decreases. The present study examined the association between time spent walking, life expectancy and lifetime medical expenditure.
The authors followed up 27 738 participants aged 40–79 years and prospectively collected data on their medical expenditure and survival covering a 13-year-period. Participants were classified into those walking <1 and ≥1 h per day. The authors constructed life tables and estimated the life expectancy and lifetime medical expenditure from 40 years of age using estimate of multiadjusted mortality and medical expenditure using a Poisson regression model and linear regression model, respectively.
Participants who walked ≥1 h per day have a longer life expectancy from 40 years of age than participants who walked <1 h per day. The multiadjusted life expectancy for those who walked ≥1 h per day was 44.81 years, significantly lower by 1.38 years in men (p=0.0073) in men and 57.78 years in women, non-significantly lower by 1.16 years in women (p=0.2351). In addition to their longer life expectancy, participants who walked ≥1 h per day required a lower lifetime medical expenditure from 40 years of age than participants who walked <1 h per day. The multiadjusted lifetime medical expenditure for those who walked ≥1 h per day was £99 423.6, significantly lower by 7.6% in men (p=0.0048) and £128 161.2, non-significantly lower by 2.7% in women (p=0.2559).
Increased longevity resulting from a healthier lifestyle does not necessarily translate into an increased amount of medical expenditure throughout life. Encouraging people to walk may extend life expectancy and decrease lifetime medical expenditure, especially for men.
Article summary
Article focus
Medical expenditure per month was reduced when the amount of time spent walking was increased.
Walking is associated with a decreased risk of mortality.
In view of the increased life expectancy of those who walk longer, it is unclear whether lifetime medical expenditure increases or decreases as a result.
Key messages
Lifetime medical expenditure from the age of 40 years for men and women who walked ≥1 h per day was reduced by 7.6% and 2.7%, respectively, in comparison with those who walked <1 h per day.
Years of life added as a result of a healthy lifestyle did not necessarily translate into an increased amount of lifetime medical expenditure.
Strengths and limitations of this study
This is the first study to investigate the association between walking, life expectancy and lifetime medical expenditure.
We assessed walking using a simple questionnaire, in which we asked the participants to report only the time spent walking, and did not ask about walking pace, distance walked or any distinction between walking for exercise and other reasons.
PMCID: PMC3191604  PMID: 22021866
13.  Attributable Fractions of Risk Factors for Cardiovascular Diseases 
Journal of Epidemiology  2011;21(2):81-86.
Cardiovascular disease (CVD) is a leading cause of death in Japan. To reduce the threat of CVD, it is important to identify its major risk factors. The population attributable fraction (PAF) is calculated from the prevalence and relative risk of risk factors and can be used to estimate the burden of these factors with respect to CVD. We analyzed the findings from several prospective studies to determine the PAFs of CVD.
PAF was calculated as pd × (multiadjusted relative risk − 1)/multiadjusted relative risk, where pd is the proportion of patients exposed to that risk factor category, according to data from the Ohsaki Cohort Study, EPOCH-JAPAN, NIPPON DATA80, Miyagi Cohort Study, CARDIA Study, and ARIC Study.
Nonoptimal blood pressure explained 47% and 26% of CVD mortality in middle-aged and elderly Japanese, respectively. Cigarette smoking explained 34% of all-cause mortality in middle-aged men. The combination of hypertension and cigarette smoking explained 57% and 44% of CVD mortality in younger men and women, respectively. Furthermore, the presence of at least 1 nonoptimal risk factor explained most CVD deaths and all-cause deaths.
Established CVD risk factors, especially high blood pressure and cigarette smoking, explained a large proportion of CVD mortality and all-cause mortality. Prevention, early detection, and treatment of these conventional risk factors are required to reduce mortality risk.
PMCID: PMC3899498  PMID: 21293069
cohort study; cardiovascular diseases; population attributable fraction
14.  Passive Smoke Exposure and Circulating Carotenoids in the CARDIA Study 
Annals of Nutrition & Metabolism  2010;56(2):113-118.
Our objective was to assess associations between passive smoke exposure in various venues and serum carotenoid concentrations.
CARDIA is an ongoing longitudinal study of the risk factors for subclinical and clinical cardiovascular disease. At baseline in 1985/1986, serum carotenoids were assayed and passive smoke exposure inside and outside of the home and diet were assessed by self-report. Our analytic sample consisted of 2,633 black and white non-smoking adults aged 18–30 years.
Greater total passive smoke exposure was associated with lower levels of the sum of the three provitamin A carotenoids, α-carotene, β-carotene, and β-cryptoxanthin (–0.048 nmol/l per hour of passive smoke exposure, p = 0.001), unassociated with lutein/zeaxanthin, and associated with higher levels of lycopene (0.027 nmol/l per hour of passive smoke exposure, p = 0.010) after adjustment for demographics, diet, lipid profile, and supplement use. Exposure in both home and non-home spaces was also associated with lower levels of the provitamin A carotenoid index.
Cross-sectionally, in 1985/86, passive smoke exposure in various venues was associated with reduced levels of provitamin A serum carotenoids.
PMCID: PMC2842165  PMID: 20110671
Carotenoids; Micronutrients; Occupational health; Passive smoking; Smoke exposure; Tobacco smoke pollution
15.  Effect of Age on the Association between Body Mass Index and All-Cause Mortality: The Ohsaki Cohort Study 
Journal of Epidemiology  2010;20(5):398-407.
To clarify the effect of age on the association between body mass index (BMI) and all-cause mortality.
We followed 43 972 Japanese participants aged 40 to 79 years for 12 years. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs), using the following BMI categories: <18.5 (underweight), 18.5–20.9, 21.0–22.9, 23.0–24.9 (reference), 25.0–27.4, 27.5–29.9, and ≥30.0 kg/m2 (obese). Analyses were stratified by age group: middle-aged (40–64 years) vs elderly (65–79 years).
We observed a significantly increased risk of mortality in underweight elderly men: the multivariate HR was 1.26 (0.92–1.73) in middle-aged men and 1.49 (1.26–1.76) in elderly men. In addition, we observed a significantly increased risk of mortality in obese middle-aged men: the multivariate HR was 1.71 (1.17–2.50) in middle-aged men and 1.25 (0.87–1.80) in elderly men. In women, there was an increased risk of mortality irrespective of age group in the underweight: the multivariate HR was 1.46 (0.96–2.22) in middle-aged women and 1.47 (1.19–1.82) in elderly women. There was no excess risk of mortality with age in obese women: the multivariate HR was 1.47 (0.94–2.27) in middle-aged women and 1.26 (0.95–1.68) in elderly women.
As compared with the reference category, obesity was associated with a high mortality risk in middle-aged men, whereas underweight, rather than obesity, was associated with a high mortality risk in elderly men. In women, obesity was associated with a high mortality risk during middle age; underweight was associated with a high mortality risk irrespective of age. The mortality risk due to underweight and obesity may be related to sex and age.
PMCID: PMC3900835  PMID: 20699601
body mass index; mortality; age effect; underweight; obesity
16.  Circulating Carotenoid Concentrations and Incident Hypertension: The Coronary Artery Risk Development in Young Adults (CARDIA) study 
Journal of hypertension  2009;27(2):237-242.
Several epidemiological studies have demonstrated that carotenoid concentrations relate inversely to cardiovascular disease incidence. Thus, we examined the association of circulating carotenoids with hypertension, a major macrovascular disease risk factor.
Black and white men and women in the Coronary Artery Risk Development in Young Adults (CARDIA) Study, aged 18 to 30 years at recruitment (1985–1986) from 4 US cities, were investigated over 20 years. At years 0, 7, and 15, we determined the relationships of the sum of 4 serum carotenoids (α-carotene, β-carotene, lutein/zeaxanthin, cryptoxanthin) and of lycopene with incident hypertension using proportional hazards regression models.
In 4412 participants, year 0 sum of 4 carotenoids was significantly inversely associated with 20 year hypertension incidence after adjustment for baseline systolic blood pressure and other confounding factors (relative hazard per SD increase of sum of 4 carotenoids: 0.91; 95% confidence interval: 0.84–0.99). The inverse relationship persisted in time-dependent models updating year 0 sum of 4 carotenoids with year 7 and year 15 values (relative hazard per SD increase of sum of 4 carotenoids: 0.84; 95% confidence interval: 0.77–0.92). Lycopene was unrelated to hypertension in any model.
Those with higher concentrations of sum of carotenoids, not including lycopene, generally had lower risk for future hypertension.
PMCID: PMC2920800  PMID: 19155781
Antioxidant; Carotenoids; Epidemiology; Hypertension; Prospective studies
17.  Population Attributable Fraction of Smoking and Metabolic Syndrome on Cardiovascular Disease Mortality in Japan: a 15-Year Follow Up of NIPPON DATA90 
BMC Public Health  2010;10:306.
Smoking and metabolic syndrome are known to be related to cardiovascular diseases (CVD) risk. In Asian countries, prevalence of obesity has increased and smoking rate in men is still high. We investigated the attribution of the combination of smoking and metabolic syndrome (or obesity) to excess CVD deaths in Japan.
A cohort of nationwide representative Japanese samples, a total of 6650 men and women aged 30-70 at baseline without history of CVD was followed for 15 years. Multivariate-adjusted hazard ratio for CVD death according to the combination of smoking status and metabolic syndrome (or obesity) was calculated using Cox proportional hazard model. Population attributable fraction (PAF) of CVD deaths was calculated using the hazard ratios.
During the follow-up period, 87 men and 61 women died due to CVD. The PAF component of CVD deaths in non-obese smokers was 36.8% in men and 11.3% in women, which were higher than those in obese smokers (9.1% in men and 5.2% in women). The PAF component of CVD deaths in smokers without metabolic syndrome was 40.9% in men and 11.9% in women, which were also higher than those in smokers with metabolic syndrome (7.1% in men and 3.9% in women).
Our results indicated that a large proportion of excess CVD deaths was observed in smokers without metabolic syndrome or obesity, especially in men. These findings suggest that intervention targeting on smokers, irrespective of the presence of metabolic syndrome, is still important for the prevention of CVD in Asian countries.
PMCID: PMC2894774  PMID: 20525280
18.  Dietary patterns associated with fall-related fracture in elderly Japanese: a population based prospective study 
BMC Geriatrics  2010;10:31.
Diet is considered an important factor for bone health, but is composed of a wide variety of foods containing complex combinations of nutrients. Therefore we investigated the relationship between dietary patterns and fall-related fractures in the elderly.
We designed a population-based prospective survey of 1178 elderly people in Japan in 2002. Dietary intake was assessed with a 75-item food frequency questionnaire (FFQ), from which dietary patterns were created by factor analysis from 27 food groups. The frequency of fall-related fracture was investigated based on insurance claim records from 2002 until 2006. The relationship between the incidence of fall-related fracture and modifiable factors, including dietary patterns, were examined. The Cox proportional hazards regression model was used to examine the relationships between dietary patterns and incidence of fall-related fracture with adjustment for age, gender, Body Mass Index (BMI) and energy intake.
Among 877 participants who agreed to a 4 year follow-up, 28 suffered from a fall-related fracture. Three dietary patterns were identified: mainly vegetable, mainly meat and mainly traditional Japanese. The moderately confirmed (see statistical methods) groups with a Meat pattern showed a reduced risk of fall-related fracture (Hazard ratio = 0.36, 95% CI = 0.13 - 0.94) after adjustment for age, gender, BMI and energy intake. The Vegetable pattern showed a significant risk increase (Hazard ratio = 2.67, 95% CI = 1.03 - 6.90) after adjustment for age, gender and BMI. The Traditional Japanese pattern had no relationship to the risk of fall-related fracture.
The results of this study have the potential to reduce fall-related fracture risk in elderly Japanese. The results should be interpreted in light of the overall low meat intake of the Japanese population.
PMCID: PMC2895588  PMID: 20513246
19.  The Ohsaki Cohort 2006 Study: Design of Study and Profile of Participants at Baseline 
Journal of Epidemiology  2010;20(3):253-258.
Large-scale cohort studies conducted in Japan do not always include psychosocial factors as exposures. In addition, such studies sometimes fail to satisfactorily evaluate disability status as an outcome.
This prospective cohort study comprised 49 603 (22 438 men and 27 165 women) community-dwelling adults aged 40 years or older who were included in the Residential Registry for Ohsaki City, Miyagi Prefecture, in northeastern Japan. The baseline survey, which included psychosocial factors, was conducted in December 2006. Follow-up of death, immigration, cause of death, cancer incidence, and long-term care insurance certification was started on 1 January 2007.
The response rate was 64.2%. In general, lifestyle-related conditions in the study population were similar to those of the general Japanese population; however, the proportion of male current smokers was higher in the cohort. The association between age and the proportion of those reporting psychological distress showed a clear U-shaped curve, with a nadir at age 60 to 69 years in both men and women, although more women were affected by such distress than men. The proportion of those who reported a lack of social support was highest among those aged 40 to 49 years. Most men and women surveyed did not participate in community activities. Among participants aged 65 years or older, 10.9% of participants were certified beneficiaries of the long-term care insurance system at baseline.
The Ohsaki Cohort 2006 Study is a novel population-based prospective cohort study that focuses on psychosocial factors and long-term care insurance certification.
PMCID: PMC3900849  PMID: 20410670
long-term care insurance; population-based; psychosocial factors; study design; the Ohsaki Cohort 2006 Study
20.  Cholesteryl Ester Transfer Protein, Coronary Calcium and Intima-media Thickness of the Carotid Artery in Middle-Aged Japanese Men 
The American journal of cardiology  2009;104(6):818-822.
The relationship between cholesteryl ester transfer protein (CETP) levels and atherosclerosis is controversial. We examined whether serum CETP levels were associated with subclinical atherosclerosis independent of its most common gene variant in a sample of Japanese men. A population-based cross-sectional study in 250 Japanese men aged 40–49 was conducted to assess intima-media thickness of the carotid artery (IMT), coronary artery calcium (CAC), serum CETP levels, and the CETP D442G gene variant. Compared with the lowest CETP quartile, multivariate adjusted odds ratios for CAC were 0.77 (95 % confidence interval [CI], 0.18 to 3.36), 0.96 (95% CI, 0.27 to 3.40), and 3.49 (95% CI, 1.05 to 11.6) with rising CETP quartiles. Serum CETP quartiles were also positively associated with IMT (adjusted means were 600, 616, 617 and 646 [μm] in the bottom to top quartiles). Findings remained unchanged after further adjustment for the CETP D442G gene variant. There was no significant difference in the prevalence of CAC, or in the mean IMT, between participants with and without the CETP D442G gene variant.
PMCID: PMC2830799  PMID: 19733717
cholesteryl ester transfer protein; coronary calcium; intima-media thickness; gene variant
21.  Absolute and Attributable Risks of Heart Failure Incidence in Relation to Optimal Risk Factors 
Circulation. Heart failure  2009;2(1):11-17.
Epidemiologic studies have shown that a large proportion of coronary heart disease and stroke events are explained by borderline or elevated risk factors, and that adults with optimal risk factors greatly avoid these events. The degree to which this applies to heart failure incidence is not well documented.
Methods and Results
We categorized baseline (1987–89) risk factors in the Atherosclerosis Risk in Communities Study cohort (n = 13,460, aged 45–64) into optimal, borderline, and elevated groups based on national guidelines, using a 4-factor score (blood pressure, plasma cholesterol, diabetes, and smoking) and a 5-factor score (body mass also). Incidence of hospitalized heart failure (n =1,344) was identified over a 16-year period. Only 4.9% of the cohort at baseline had all optimal risk factors based on the 4-factor score and 2.6% using the 5-factor score. Compared to participants with any elevated risk factor using the 4-factor score, the age-, sex-, race-adjusted relative hazard for heart failure events was 0.18 (95% CI 0.10–0.32) for those with all optimal risk factors and 0.35 (95% CI 0.30–0.41) for those with borderline risk factors only. A population attributable fraction estimate suggested that having at least one of the four risk factors, elevated or borderline, accounted for 77.1% of heart failure events. For the 5-factor score, that percentage was 88.8%.
Middle-aged adults with optimal (low) risk factors have low incidence rates of heart failure, which supports redoubled efforts to prevent risk factor development in the first place.
PMCID: PMC2637354  PMID: 19808310
epidemiology; heart failure; risk factors
22.  Factors Associated With Psychological Distress in a Community-Dwelling Japanese Population: The Ohsaki Cohort 2006 Study 
Journal of Epidemiology  2009;19(6):294-302.
In Asia, there has been no population-based epidemiological study using the K6, a 6-item instrument that assesses nonspecific psychological distress.
Using cross-sectional data from 2006, we studied 43 716 (20 168 men and 23 548 women) community-dwelling people aged 40 years or older living in Japan. We examined the association between psychological distress and demographic, medical, lifestyle, and social factors by using the K6, with psychological distress defined as 13 or more points out of a total of 24 points.
The following variables were significantly associated with psychological distress among the population: female sex, young and old age, a history of serious disease (hypertension, diabetes mellitus, stroke, myocardial infarction, or cancer), current smoking, former alcohol drinking, low body mass index, shorter daily walking time, lack of social support (4 of 5 components), and lack of participation in community activities (4 of 5 components). Among men aged 40 to 64 years, only “lack of social support for consultation when in trouble” and a history of diabetes mellitus remained significant on multivariate analysis. Among men aged 65 years or older, age was not significantly associated with psychological distress, and the significant association with current smoking disappeared on multivariate analysis. Among women aged 40 to 64 years, a history of stroke was not associated with psychological distress. Among women aged 65 years or older, the significant association with current smoking disappeared on multivariate analysis.
A number of factors were significantly associated with psychological distress, as assessed by the K6. These factors differed between men and women, and also between middle-aged and elderly people.
PMCID: PMC3924098  PMID: 19749498
cross-sectional; K6; population-based; psychological distress
23.  Relationships of Circulating Carotenoid Concentrations with Several Markers of Inflammation, Oxidative Stress, and Endothelial Dysfunction: The Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) Study 
Clinical chemistry  2007;53(3):447-455.
Serum carotenoid concentrations relate inversely to cardiovascular disease incidence. To clarify the effect of carotenoids on atherosclerotic risk factors, we examined the association of circulating carotenoids with inflammation, oxidative stress, endothelial dysfunction, and smoking.
Black and white men and women in the Coronary Artery Risk Development in Young Adults study, ages 18 to 30 years at recruitment (1985–1986) from 4 US cities, were investigated over 15 years. We included 2048 to 4580 participants in analyses of the sum of serum α-carotene, β-carotene, zeaxanthin/lutein, and β-cryptoxanthin concentrations and of lycopene at year 0 and at year 7.
The year 0 sum of 4 carotenoids was inversely associated (all P <0.05) with year 0 leukocyte count (slope per sum carotenoid SD, −0.17); year 7 fibrinogen (slope, −0.10); year 7 and year 15 C-reactive protein (slope, −0.12 and −0.09); and year 15 F2-isoprostanes (slope, −13.0), soluble P-selectin (slope, −0.48), and soluble intercellular adhesion molecule-1 (sICAM1; slope, −5.1). Leukocyte counts and sICAM1 and F2-isoprostane concentrations had stronger associations in smokers than in nonsmokers, and sICAM1 concentrations were higher in the highest carotenoid quartile in smokers than in the lowest carotenoid quartile in nonsmokers. Superoxide dismutase was positively associated with the sum of 4 carotenoids (slope, 0.12; P <0.01). Lycopene was inversely associated only with sICAM1. The year 7 carotenoid associations with these markers were mostly similar to those at year 0.
Circulating serum carotenoids were associated, some interactively with smoking, in apparently beneficial directions with markers of inflammation, oxidative stress, and endothelial dysfunction.
PMCID: PMC2440581  PMID: 17234732

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