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.
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.
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.
Aims: Few studies have investigated the subclinical atherosclerotic changes in the brain and carotid artery, and in East Asian populations. We sought to investigate whether gravidity, delivery, the ...age at menarche and menopause and estrogen exposure period are associated with subclinical atherosclerosis of the brain and carotid arteriopathy.Methods: This cross-sectional study formed part of a cohort study of Ohasama residents initiated in 1986. Brain atherosclerosis and carotid arteriopathy were diagnosed as white matter hyperintensity (WMH) and lacunae evident on brain magnetic resonance imaging (MRI) and carotid intimal media thickness (IMT) or plaque revealed by ultrasound, respectively. The effect of the reproductive events on brain atherosclerosis and carotid arteriopathy was investigated using logistic regression and general linear regression models after adjusting for covariates.Results: Among 966 women aged ≥ 55 years in 1998, we identified 622 and 711 women (mean age: 69.2 and 69.7 years, respectively) who underwent either MRI or carotid ultrasound between 1992–2008 or 1993–2018, respectively. The highest quartile of gravidity (≥ 5 vs. 3) and delivery (≥ 4 vs. 2), and the highest and second highest (3 vs. 2) quartiles of delivery were associated with an increased risk of WMH and carotid artery plaque, respectively. Neither of age at menarche, menopause, and estrogen exposure period estimated by subtracting age at menarche from age at menopause was associated with atherosclerotic changes of brain and carotid arteries.Conclusions: Higher gravidity and delivery are associated with subclinical atherosclerosis of the brain and carotid plaque.
Aim: Few studies have addressed stroke risk factors in older populations, particularly among the old-old. We examined differences in traditional risk factors for stroke among the old-old compared ...with the young-old in community-dwelling Japanese adults.Methods: We followed 2,065 residents aged ≥ 60 years who had no history of stroke. Traditional risk factors for stroke were obtained from a self-administered questionnaire at baseline. We classified participants into two age categories, 60–74 years (n=1,502) and ≥ 75 years (n=563), and assessed whether traditional risk factors were differentially associated with stroke incidence according to age category. Hazard ratios were calculated by the Cox proportional hazards model, adjusting for confounding factors and competing risk of death.Results: During a median follow-up of 12.8 and 7.9 years, 163 and 111 participants aged 60–74 and ≥ 75 years, respectively, developed a first stroke. Hypertension was consistently associated with increased risk of stroke, regardless of age category. Diabetes mellitus was associated with increased risk of stroke in those aged 60–74 years (hazard ratio, 1.50; 95% confidence interval, 1.00–2.25), but not in those aged ≥ 75 years (hazard ratio, 0.65; 95% confidence interval, 0.33–1.29), with significant interaction by age (P=0.035). No traditional risk factor other than hypertension was associated with stroke among those aged ≥ 75 years.Conclusion: Those with hypertension had significantly higher stroke risk among old people, while diabetes mellitus was differentially associated with stroke according to age category. Our findings indicate the importance of different prevention strategies for stroke incidence according to age category.
Small intestinal mononuclear cells that express CX3CR1 (CX3CR1
cells) regulate immune responses
. CX3CR1
cells take up luminal antigens by protruding their dendrites into the lumen
. However, it ...remains unclear how dendrite protrusion by CX3CR1
cells is induced in the intestine. Here we show in mice that the bacterial metabolites pyruvic acid and lactic acid induce dendrite protrusion via GPR31 in CX3CR1
cells. Mice that lack GPR31, which was highly and selectively expressed in intestinal CX3CR1
cells, showed defective dendrite protrusions of CX3CR1
cells in the small intestine. A methanol-soluble fraction of the small intestinal contents of specific-pathogen-free mice, but not germ-free mice, induced dendrite extension of intestinal CX3CR1
cells in vitro. We purified a GPR31-activating fraction, and identified lactic acid. Both lactic acid and pyruvic acid induced dendrite extension of CX3CR1
cells of wild-type mice, but not of Gpr31b
mice. Oral administration of lactate and pyruvate enhanced dendrite protrusion of CX3CR1
cells in the small intestine of wild-type mice, but not in that of Gpr31b
mice. Furthermore, wild-type mice treated with lactate or pyruvate showed an enhanced immune response and high resistance to intestinal Salmonella infection. These findings demonstrate that lactate and pyruvate, which are produced in the intestinal lumen in a bacteria-dependent manner, contribute to enhanced immune responses by inducing GPR31-mediated dendrite protrusion of intestinal CX3CR1
cells.