Megumi Utsugi

Fruit and Vegetable Consumption and the Risk of Hypertension Determined by Self Measurement of Blood Pressure at Home: The Ohasama Study

It is well recognized that high fruit and vegetable consumption is associated with a reduction of blood pressure (BP) measured by conventional BP measurement in Western countries; however, there is little evidence about these associations in other regions and there have been no reports on these associations using selfmeasured BP at home (home BP). The objective of this work was to investigate the associations of fruit and vegetable consumption and their related micronutrients with the reduction of hypertension risk by using home BP in Japanese residents. Data were obtained from 1,569 residents aged 35 and over who measured their home BP in a general population of Ohasama, Japan. Dietary intake was measured using a 141-item food-frequency questionnaire (FFQ) and then subjects were divided into tertiles according to fruit, vegetable, potassium, vitamin C, and β-carotene consumption. Hypertension was defined as home systolic/diastolic BP≥ 135/85 mmHg and/or the use of antihypertensive medication. The prevalence of home hypertension was 39.4% for men and 29.3% for women. After adjustment for all potential confounding factors, the highest-tertile consumptions of fruits, vegetables, potassium, and vitamin C were associated with a significantly lower risk of hypertension (45%, 38%, 46%, and 43% lower risk of home hypertension, respectively). In conclusion, this cross-sectional study based on home BP measurement suggests that high-level consumptions of fruits, vegetables, potassium, and vitamin C are associated with a significantly lower risk of hypertension.

Relationship of beta2-microglobulin to arterial stiffness in Japanese subjects.

β2-Microglobulin (β2m) is related to inflammatory diseases, but there have been few reports of a relationship between β2m and atherosclerosis. We have examined the influence of β2m on brachial-ankle pulse wave velocity (baPWV) to clarify whether it is related to arterial stiffness. baPWV, β2m, C-reactive protein (CRP), and conventional risk factors were measured in 614 males and 158 females. The adjusted means of baPWV were compared with the quartiles of β2m, and significant differences in baPWV were observed across the quartiles of β2m (p=0.037). After being adjusted for potential confounders, quartile 4 of β2m, quartile 4 of CRP, and the combination of high β2m plus high CRP were significantly associated with a high value of PWV (quartile 4 of β2m: odds ratio [OR] 2.53, 95% confidence interval [CI], 1.31–4.89; quartile 4 of CRP: OR 2.27, 95% CI, 1.18–4.34; high β2m plus high CRP: OR 5.60, 95% CI, 2.38–13.2). These results suggest that β2m is associated with an increase of arterial stiffness. Further studies are needed to clarify whether β2m is related to atherosclerotic diseases, and whether the combination of β2m and CRP measurement is a useful predictor for the development of atherosclerosis.

Relationships of C-reactive protein, uric acid, and glomerular filtration rate to arterial stiffness in Japanese subjects

The relationships between C-reactive protein (CRP), uric acid (UA), glomerular filtration rate (GFR), and arterial stiffness have not been fully investigated. The aim of this study was to clarify whether CRP, UA, and estimated GFR are related to arterial stiffness estimated using brachial-ankle pulse wave velocity (baPWV). The subjects were local government employees (3412 men and 854 women). baPWV, CRP, UA, GFR, and conventional risk factors were evaluated. Multiple linear regression analyses revealed that CRP and UA were significantly related to an elevation of PWV in male and female subjects, and that the estimated GFR was significantly related to an elevation of PWV in male subjects. Significant progressive increases in baPWV were observed across the quartiles of CRP in male subjects and for UA in male and female subjects. In female subjects, the relationship of quartile CRP to baPWV had marginal significance (P=0.055). But, in male and female subjects, quartile of estimated GFR had no significant association with PWV. These results suggest that CRP and UA are associated with an increase of arterial stiffness in male and female subjects, and that estimated GFR is possibly related to arterial stiffness in male subjects.

Relationship of Helicobacter pylori Infection to Arterial Stiffness in Japanese Subjects

The role of Helicobacter pylori in the pathogenesis of atherosclerosis remains controversial, and the relationship between H. pylori and the early stage of atherosclerosis has not been fully investigated. We investigated the influence of H. pylori infection on arterial stiffness to clarify whether H. pylori infection is related to early-stage atherosclerosis. The subjects were 3,412 males and 854 females. Anti-H. pylori antibody and C-reactive protein (CRP) level were measured. Arterial stiffness was evaluated using the brachial-ankle pulse wave velocity (PWV). In multivariate logistic repression analyses of male subjects, H. pylori seropositivity (odds ratio [OR] 1.27 [95% confidence interval, 1.05–1.52]) and H. pylori seropositivity with a high CRP value (>0.045 mg/dl) (OR 1.50 [1.14–1.98]) were significantly related to a high value of PWV. In the analyses of male subjects aged ≤49 years, H. pylori seropositivity (OR 1.40 [1.04–1.88]) and H. pylori seropositivity with a high CRP value (OR 1.81 [1.16–2.80]) were also significantly related to a high value of PWV. However, in male subjects aged ≥50 years and female subjects, no associations were found. These results suggest that inflammation following H. pylori infection contributes to the early stage of atherosclerosis in younger males.

Aldosterone-to-renin ratio and nocturnal blood pressure decline in a general population: the Ohasama study.

Background Aldosterone-to-renin ratio (ARR) is an index for inappropriate aldosterone activity and salt sensitivity. We previously reported that elevated ARR might be associated with salt-sensitive hypertension. Because salt-sensitive hypertensive patients are reported to show a diminished nocturnal decline in blood pressure, we hypothesized that high ARR may be associated with diminished nocturnal decline in blood pressure (generally referred to as a ‘nondipping’ pattern), especially in individuals with high sodium intake. Methods This study tested this hypothesis in 184 participants aged at least 55 years not receiving antihypertensive treatment in a general Japanese population (age: 67.6 ± 6.9 years; 71.7% women). Results Ambulatory blood pressure monitoring identified 63 (34.2%) participants with a nondipping pattern (nocturnal decline of SBP <10%). The median plasma renin activity (PRA), plasma aldosterone concentration (PAC), and ARR were 0.8 ng/ml per h, 8.3 ng/dl, and 8.7 ng/dl per (ng/ml per h), respectively. After adjustment for possible confounding factors, each 1 SD increase in logARR was associated with the prevalence of nondipping pattern (odds ratio, 1.95; P = 0.002). This association was observed in individuals in the highest tertile of 24-h urinary sodium excretion estimated from spot urine data (e24-hUNa; ≥179.6 mEq/day; P = 0.01) but disappeared in those in the lowest tertile of e24-hUNa (<147.9 mEq/day; P = 0.6). In those in the highest tertile of e24-hUNa, PRA was significantly lower in nondippers than in dippers (0.49 vs. 0.85 ng/ml per h) despite no differences in PAC. Conclusion These results suggest that relative aldosterone excess might be related to a nondipping pattern of blood pressure, especially in individuals with high sodium intake.

Aldosterone-to-Renin Ratio as a Predictor of Stroke Under Conditions of High Sodium Intake: The Ohasama Study

BACKGROUND Aldosterone is thought to have deleterious effects on the cardiovascular system. The aldosterone-to-renin ratio (ARR) is more reproducible than aldosterone levels alone and could be an index for inappropriate aldosterone secretion or activity. We previously reported the apparent relation between ARR and hypertension in subjects with high sodium intake. This prospective study investigated the risk of ARR for a first stroke in a general population stratified by sodium intake. METHODS We obtained plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) for 883 participants aged ≥ 35 years not receiving antihypertensive treatment in the general population of Ohasama (mean age: 59.0 ± 11.3 years; 65.6% women). RESULTS Over a mean of 10.9 follow-up years, 45 strokes occurred. The median PRA, PAC, and ARR were 1.2 ng/ml/h, 6.4 ng/dl, and 5.3 ng/dl per ng/ml/h, respectively. Using Cox regression, we computed hazard ratios adjusted for sex, age, body mass index (BMI), and systolic blood pressure. No association between logARR and stroke was observed in subjects overall. However, in subjects with high sodium intake (≥ median of 4,058 mg/day (salt equivalent, 10.5 g/day)), each 1 s.d. increase in logARR was associated with an increased hazard ratio for stroke (hazard ratio: 1.49, P = 0.04). No significant association was observed in subjects with low sodium intake (P = 0.7). When we repeated all the analyses using logPRA or logPAC, no significant associations were found. CONCLUSION These results suggest that high ARR, that is, relative aldosterone excess, is a predictor for stroke under conditions of high sodium intake.

Aldosterone-to-renin ratio and home blood pressure in subjects with higher and lower sodium intake: the Ohasama Study

Aldosterone-to-renin ratio (ARR) is used to screen primary hyperaldosteronism. We investigated the association between ARR and the prevalence of hypertension using home blood pressure (HBP) measurements in community residents stratified for long-term habitual dietary sodium intake. We obtained HBP and conventional blood pressure (CBP) data for 514 participants aged ⩾35 years not receiving antihypertensive treatment in the general population of Ohasama (mean age: 59.7±10.8 years; 71.2% women). A standardized method was used to calculate habitual sodium intake from a food-frequency questionnaire. The prevalence of HBP hypertension (⩾135/85 mm Hg) and CBP hypertension (⩾140/90 mm Hg) were 12.6 and 20.2%, respectively. The median plasma renin activity (PRA), plasma aldosterone concentration (PAC) and ARR were 1.1 ng ml–1 h–1, 6.4 ng per 100 ml and 5.5 ng per 100 ml per ng ml–1 h–1, respectively. After adjustment for possible confounding factors, each 1 s.d. increase in logARR was associated with the prevalence of HBP hypertension (odds ratio 1.37; P=0.04), but not with the prevalence of CBP hypertension (P=0.2). The association of ARR with HBP hypertension was strengthened for subjects with high sodium intake (greater than or equal to the median of 4822 mg day–1), whereas it became nonsignificant for those with low sodium intake (interaction P=0.03). Among subjects with high sodium intake, HBP hypertensives had significantly lower PRA than normotensives, despite no differences in PAC. In conclusion, relative aldosterone excess or low-renin hypertension may have an important role in HBP hypertension in the general population with high sodium intake.

Inflammation as a cardiovascular risk factor and pulse wave velocity as a marker of early-stage atherosclerosis in the Japanese population

Inflammation and pulse wave velocity (PWV) are a potential risk factor and marker, respectively, for atherosclerosis in the primary prevention setting. Atherosclerosis is now generally accepted to be an inflammatory disorder of the arterial wall, and the high-sensitivity C-reactive protein (hs-CRP) level has been reported to be a strong predictor of cardiovascular events. High-sensitivity-CRP is associated with two factors related to inflammation: (1) the local production of CRP by atheromatous tissue or coronary artery smooth muscle cells and (2) adipose tissue as a potent source of inflammatory cytokines. Based on studies in North America and Europe, hs-CRP has been established as a cardiovascular risk factor and a cut-off value has been recommended. However, Japanese have lower hs-CRP values than their Western counterparts, partly because Japanese have a lower body mass index (BMI), which correlates positively to hs-CRP, and partly because lifestyle and genetic factors can affect hs-CRP values. Therefore, a cut-off value needs to be established by cohort studies for the Japanese population. Carotid-femoral PWV is most commonly measured by applanation tonometry, particularly in Europe, but this method is critically dependent upon the accurate placing of transducers over the arteries and is both time-consuming and complex. A novel device has been recently developed in Japan that measures brachial-ankle PWV (baPWV) using a volume-rendering method. Brachian-ankle PWV is a suitable screening method because of its technical simplicity and shorter measurement time. It is associated not only with conventional cardiovascular risk factors but also with new risk factors, such as inflammation, γ-glutamyltransferase, chronic kidney disease, and psychosocial factors. However, a suitable cut-off value has yet to be established.

Aldosterone-to-renin ratio and nocturnal blood pressure decline assessed by self-measurement of blood pressure at home: the Ohasama Study

Abstract Based on ambulatory blood pressure (BP) monitoring, the aldosterone-to-renin ratio (ARR) has been reported to be associated with a diminished nocturnal decline in BP, generally referred to as a “non-dipping” pattern. The objective of this cross-sectional study was to investigate the association between ARR and the non-dipping pattern based on home BP measurements. This study included 177 participants ≥55 years from the general population of Ohasama (mean age: 67.2 years; 74.6% women); no patient was receiving antihypertensive treatment. The median plasma renin activity (PRA), plasma aldosterone concentration (PAC) and ARR were 0.8 ng/mL/h, 8.1 ng/dL and 9.7 ng/dL per ng/mL/h, respectively. Each 1 SD increase in log-transformed (ln) ARR was significantly associated with the prevalence of the non-dipping pattern after adjustments for possible confounding factors including home morning systolic BP (odds ratio, 1.45; p = 0.049). However, no significant associations of PRA or PAC with the non-dipping pattern were observed (p ≥ 0.2). When participants were divided into four groups according to median levels of home morning and night-time systolic BPs, the group with a higher home morning systolic BP (≥128.4 mmHg) with a higher home night-time systolic BP (≥114.4 mmHg) had the greatest ARR levels (ANCOVA p = 0.01). These results support the hypothesis that relative aldosterone excess may be related to a non-dipping pattern in a general population and suggest that a non-dipping pattern can be accurately observed by home BP measurements.

432 ALDOSTERONE-TO-RENIN RATIO AS A PREDICTOR OF STROKE UNDER CONDITIONS OF HIGH SODIUM INTAKE: THE OHASAMA STUDY

Background: Aldosterone is thought to have deleterious effects on the cardiovascular system. The aldosterone-to-renin ratio (ARR) is more reproducible than aldosterone levels alone and could be an index for inappropriate aldosterone secretion or activity. We previously reported the apparent relation between ARR and hypertension in subjects with high sodium intake. This prospective study investigated the risk of ARR for a first stroke in a general population stratified by sodium intake. Methods: We obtained plasma renin activity (PRA) and plasma aldosterone concentrations (PAC) for 883 participants aged ≥35 years not receiving antihypertensive treatment in the general population of Ohasama (mean age: 59.0 ± 11.3 years; 65.6% women). Results: Over a mean of 10.9 follow-up years, 45 strokes occurred. The median PRA, PAC, and ARR were 1.2 ng/mL/h, 6.4 ng/dL, and 5.3 ng/dL per ng/mL/h, respectively. Using Cox regression, we computed hazard ratios adjusted for sex, age, body mass index, and systolic blood pressure. No association between logARR and stroke was observed in subjects overall. However, in subjects with high sodium intake (≥ median of 4058 mg/day [salt equivalent, 10.5 g/day]), each 1 SD increase in logARR was associated with an increased hazard ratio for stroke (hazard ratio: 1.49, P = 0.04). No significant association was observed in subjects with low sodium intake (P = 0.7). When we repeated all the analyses using logPRA or logPAC, no significant associations were found. Conclusion: These results suggest that high ARR, that is, relative aldosterone excess, is a predictor for stroke under conditions of high sodium intake.