The sodium-to-potassium (Na/K) ratio is known to be associated with blood pressure (BP). However, no reference value has been established since the urinary Na/K (uNa/K) ratio is known to have diurnal ...and day-to-day variations. Therefore, we investigated the number of days required to yield a better association between the morning uNa/K ratio and home BP (HBP) and determined a morning uNa/K ratio value that can be used as a reference value in participants who are not taking antihypertensive medication. This was a cross-sectional study using data from the Tohoku Medical Megabank Project Cohort Study. A total of 3122 participants borrowed HBP and uNa/K ratio monitors for 10 consecutive days. We assessed the relationship between the morning uNa/K ratio from 1 day to 10 days and home hypertension (HBP ≥ 135/85 mmHg) using multiple logistic regression models. Although a 1-day measurement of the morning uNa/K ratio was positively associated with home hypertension, multiple measurements of the morning uNa/K ratio were strongly related to home hypertension. The average morning uNa/K ratio was relatively stable after 3 days (adjusted odds ratio of home hypertension per unit increase in the uNa/K ratio for more than 3 days: 1.19-1.23). In conclusion, there was no threshold for the uNa/K ratio, and the morning uNa/K ratio was linearly associated with home hypertension. The Na/K ratio 2.0 calculated from the Dietary Reference Intakes for Japanese might be a good indication. Regarding the stability of the association between the morning uNa/K ratio and BP, more than 3 days of measurements is desirable.
Hypertension guidelines recommend blood pressure self-measurement at home (HBP), but no previous trial has assessed cardiovascular outcomes in hypertensive patients treated according to HBP. The ...multicenter Hypertension Objective Treatment Based on Measurement by Electrical Devices of Blood Pressure (HOMED-BP; 2001-2010) trial involved 3518 patients (50% women; mean age 59.6 years) with an untreated systolic/diastolic HBP of 135-179/85-119 mm Hg. In a 2 × 3 design, patients were randomized to usual control (125-134/80-84 mm Hg (UC)) vs. tight control (<125/<80 mm Hg (TC)) of HBP and to initiation of drug treatment with angiotensin converting enzyme inhibitors, angiotensin receptor blockers or calcium channel blockers. During follow-up, a computer algorithm automatically generated treatment recommendations based on HBP. At the last follow-up (median 5.3 years), TC patients used more antihypertensive drugs than UC patients (1.82 vs. 1.74 defined daily doses, P=0.045) and had a greater HBP reduction (21.3/13.1 mm Hg vs. 22.7/13.9 mm Hg, P=0.018/0.020), but they less frequently achieved the lower HBP targets (37.4 vs. 63.5%, P<0.0001). The primary end point, cardiovascular death plus stroke and myocardial infarction, occurred in 25 UC and 26 TC patients (hazard ratio, 1.02; 95% confidence interval, 0.59-1.77; P=0.94). Rates were similar (P≥0.13) in the three drug groups. In all patients combined, the risk of the primary end point independently increased by 41% (6-89%; P=0.019) and 47% (15-87%; P=0.0020) for a 1-s.d. increase in baseline (12.5 mm Hg) and follow-up (13.2 mm Hg) systolic HBP. The 5-year risk was minimal (≤1%) if on-treatment systolic HBP was 131.6 mm Hg or less. HOMED-BP proved the feasibility of adjusting antihypertensive drug treatment based on HBP and suggests that a systolic HBP level of 130 mm Hg should be an achievable and safe target.
Seasonal variation of blood pressure (BP) has been reported in small populations or by BP levels captured at only a few points in a year, for example, summer and winter. We aimed to investigate the ...multiyear seasonal variation in self-measured home BP among hypertensive patients receiving antihypertensive medications. We selected 1649 eligible patients receiving antihypertensive drug treatment, and weekly averaged home BPs were analyzed throughout the follow-up period. Systolic and diastolic home BPs were fitted with the cosine function: 'Variation+Other Effects+Intercept', in which the 'Variation' was expressed by a cosine curve with three parameters representing: (1) maximum-minimum difference of home BP in one cycle of the cosine curve; (2) time required for one cycle of the cosine curve for home BP variation; and (3) time at which home BP reached the maximum point. Maximum-minimum differences in home BP were 6.7/2.9 mm Hg, and the highest home BPs were observed in mid-to-late January. In the multivariable-adjusted model, a large maximum-minimum difference in home BP was associated with lower body mass index and older age, and larger differences were observed in men compared with women. Summer-winter difference in home BP was essentially similar every year, though it was marginally reduced by 0.14/0.04 mm Hg per year, under long-term antihypertensive treatment. Records of daily home BP measurements enable us to capture long-term factors such as seasonal variation. Home BP should therefore be carefully monitored, particularly in patients with increased BP in winter, to mitigate cardiovascular risk.
The Tohoku Medical Megabank Organization reports the whole-genome sequences of 1,070 healthy Japanese individuals and construction of a Japanese population reference panel (1KJPN). Here we identify ...through this high-coverage sequencing (32.4 × on average), 21.2 million, including 12 million novel, single-nucleotide variants (SNVs) at an estimated false discovery rate of <1.0%. This detailed analysis detected signatures for purifying selection on regulatory elements as well as coding regions. We also catalogue structural variants, including 3.4 million insertions and deletions, and 25,923 genic copy-number variants. The 1KJPN was effective for imputing genotypes of the Japanese population genome wide. These data demonstrate the value of high-coverage sequencing for constructing population-specific variant panels, which covers 99.0% SNVs of minor allele frequency ≥0.1%, and its value for identifying causal rare variants of complex human disease phenotypes in genetic association studies.
Summary Background Few studies have formally compared the predictive value of the blood pressure at night over and beyond the daytime value. We investigated the prognostic significance of the ...ambulatory blood pressure during night and day and of the night-to-day blood pressure ratio. Methods We did 24-h blood pressure monitoring in 7458 people (mean age 56·8 years SD 13·9) enrolled in prospective population studies in Denmark, Belgium, Japan, Sweden, Uruguay, and China. We calculated multivariate-adjusted hazard ratios for daytime and night-time blood pressure and the systolic night-to-day ratio, while adjusting for cohort and cardiovascular risk factors. Findings Median follow-up was 9·6 years (5th to 95th percentile 2·5–13·7). Adjusted for daytime blood pressure, night-time blood pressure predicted total (n=983; p<0·0001), cardiovascular (n=387; p<0·01), and non-cardiovascular (n=560; p<0·001) mortality. Conversely, adjusted for night-time blood pressure, daytime blood pressure predicted only non-cardiovascular mortality (p<0·05), with lower blood pressure levels being associated with increased risk. Both daytime and night-time blood pressure consistently predicted all cardiovascular events (n=943; p<0·05) and stroke (n=420; p<0·01). Adjusted for night-time blood pressure, daytime blood pressure lost prognostic significance only for cardiac events (n=525; p≥0·07). Adjusted for the 24-h blood pressure, night-to-day ratio predicted mortality, but not fatal combined with non-fatal events. Antihypertensive drug treatment removed the significant association between cardiovascular events and the daytime blood pressure. Participants with systolic night-to-day ratio value of 1 or more were older, at higher risk of death, and died at an older age than those whose night-to-day ratio was normal (≥0·80 to <0·90). Interpretation In contrast to commonly held views, daytime blood pressure adjusted for night-time blood pressure predicts fatal combined with non-fatal cardiovascular events, except in treated patients, in whom antihypertensive drugs might reduce blood pressure during the day, but not at night. The increased mortality in patients with higher night-time than daytime blood pressure probably indicates reverse causality. Our findings support recording the ambulatory blood pressure during the whole day.
Recently, a high urinary sodium-to-potassium (Na/K) ratio and reduced sleep efficiency, in addition to conventional risk factors (obesity and excess alcohol intake), have been identified as risk ...factors for hypertension. We estimated the population attributable fraction (PAF) for home hypertension due to these risk factors in a general Japanese population. We conducted a cross-sectional study including 1384 participants (393 men and 991 women) to estimate the odds ratio (OR) and 95% confidence interval (CI) for the presence of any of the conventional risk factors using multivariable logistic regression analyses. The models were adjusted for sex, age, smoking status, and log-transformed average daily steps. We also estimated the OR and 95% CI for the presence of any of the overall risk factors. Furthermore, we calculated the PAF due to these risk factors. The results showed that the prevalence of home hypertension was 39.0% (540/1384). The presence of any of the conventional risk factors, as well as any of the overall risk factors, was significantly associated with an increased prevalence of hypertension (OR 2.80, 95% CI 2.15-3.65; OR 2.50, 95% CI 1.93-3.22, respectively). The PAF for hypertension due to the presence of any of the conventional risk factors and the PAF due to the presence of any of the overall risk factors were 30.2% and 39.0%, respectively. In conclusion, the impact of the overall risk factors, including the urinary Na/K ratio and sleep efficiency, on home hypertension was higher than that of conventional risk factors alone. The management of the urinary Na/K ratio and sleep efficiency as well as conventional risk factors might be important in the management of blood pressure.
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.
Numerous prospective studies have investigated the association between the number of remaining teeth and dementia or cognitive decline. However, no agreement has emerged on the association between ...tooth loss and cognitive impairment, possibly due to past studies differing in target groups and methodologies. We aimed to investigate the association between tooth loss, as evaluated through clinical oral examinations, and the development of cognitive impairment in community-dwelling older adults while considering baseline cognitive function.
This 4-year prospective cohort study followed 140 older adults (69.3% female) without cognitive impairment aged ≥65 years (mean age: 70.9 ± 4.3 years) living in the town of Ohasama, Iwate Prefecture, Japan. Cognitive function was evaluated with the Mini-Mental State Examination (MMSE) in baseline and follow-up surveys. Based on a baseline oral examination, the participants were divided into those with 0-9 teeth and those with ≥10 teeth. To investigate the association between tooth loss and cognitive impairment, we applied a multiple logistic regression analysis adjusted for age, sex, hypertension, diabetes, cerebrovascular/cardiovascular disease, hypercholesterolemia, depressive symptoms, body mass index, smoking status, drinking status, duration of education, and baseline MMSE score.
In the 4 years after the baseline survey, 27 participants (19.3%) developed cognitive impairment (i.e., MMSE scores of ≤24). Multiple logistic regression analysis indicated that participants with 0-9 teeth were more likely to develop cognitive impairment than those with ≥10 teeth were (odds ratio: 3.31; 95% confidence interval: 1.07-10.2). Age, male gender, and baseline MMSE scores were also significantly associated with cognitive impairment.
Tooth loss was independently associated with the development of cognitive impairment within 4 years among community-dwelling older adults. This finding corroborates the hypothesis that tooth loss may be a predictor or risk factor for cognitive decline.
To examine child-parent associations of HCT among Japanese adults and their parents. Factors associated with hematocrit (HCT) were analyzed in 3,574 sons and 7,203 daughters using Pearson’s ...correlation coefficient and Student’s t-test. Multiple linear regression analysis, adjusted by the factors identified by univariate analyses and by living with parents, was performed on 242 son-parent trios and 587 daughter-parent trios. When a child-parent association was observed in the multiple linear regression analysis, it was validated using the random family method (RFM). In univariate analyses, the son’s HCT was associated with age (correlation coefficient = –0.072), white blood cell (WBC) (0.19), alanine aminotransferase (ALT) (0.20), triglyceride (0.11), and estimated glomerular filtration rate (eGFR) (− 0.087). The daughter’s HCT was associated with WBC (0.014), ALT (0.18), and eGFR (− 0.17). In multiple linear regression analysis, the son’s HCT was associated with the son’s WBC (coefficient = 3.48 × 10–4), the son’s eGFR (0.031), the father’s HCT (0.11), and the mother’s HCT (0.17). RFM confirmed the association between the son’s and father’s HCT (p = 0.0070) and between the son’s and mother’s HCT (p = 0.0011). The daughter’s HCT was associated with WBC (2.6 × 10–4), ALT (0.037), and the mother’s HCT (0.14). RFM confirmed the association between the daughter’s and mother’s HCT (p = 0.00043). Child-parent association of HCT was confirmed between son-father, son–mother, and daughter-mother relationships, and differed depending on the sex of the child and the parents.
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