Effects of a Japanese Cuisine-Based Antihypertensive Diet and Fish Oil on Blood Pressure and Its Variability in Participants with Untreated Normal High Blood Pressure or Stage I Hypertension: A Feasibility Randomized Controlled Study.

AIM: The Dietary Approaches to Stop Hypertension (DASH) diet is recommended for lowering blood pressure (BP). Our previous single-arm trial revealed that the Japanese cuisine-based DASH (J-DASH) diet (supplying NaCl 8.0 g per day) reduced BP and improved cardiometabolic biomarkers. The present study's primary objective was to test the feasibility of the J-DASH diet based on its effects on the BP and BP variability of subjects with untreated high-normal BP or stage 1 hypertension. METHODS: The 6-month study period was held from December 2015 to August 2016. The participants were recruited through advertisements in local newspapers and our website and from among randomized participants at Yamaguchi University Hospital. The 2-month treatments included the following: the J-DASH-1 diet 1×/day or the J-DASH-2 diet providing a fish hamburger-patty 2×/day (5 days/week respectively). The control group consumed their usual diets. For the subsequent 4 months, all participants consumed their usual diets. The main outcome measure was the feasibility of the J-DASH diet. We also collected the data of clinic BP and home BP (by automatic BP monitor), cardiometabolic biomarkers, and lifestyle and psychosocial parameters during the intervention phase. We examined behavior changes throughout the study period, and the diets' safety. RESULTS: Fifty-one participants were recruited; following screening, 48 met the inclusion criteria and were randomized by central allocation. Eight participants were eliminated based on exclusion criteria, and the 40 participants were randomly allocated to the J-DASH 1 and J-DASH 2 groups ( n=13 each) and the usual-diet group (n=14). The participants' mean age was 50 years, and 44% were women. The three groups' clinic BP values were not significantly different, but the home BP values were lower in the J-DASH 1 group and lowest in the J-DASH 2 group compared to the usual-diet group and differed significantly among the three groups throughout the study period (p＜0.0001). The home BP variability was significantly lower in the J-DASH groups compared to the usual-diet group throughout the study period ( p＜0.01). The other indices including fish oil showed little differences among the groups throughout the study period. CONCLUSIONS: The J-DASH diet was feasible to improve home BP and stabilize its variability, and it did so more effectively than the participants' usual diets.

Clustering of cardiovascular risk factors and blood pressure control status in hypertensive patients.

OBJECTIVE: Hypertensive patients have multiple risk factors such as chronic kidney disease (CKD) and hyperuricemia in addition to components of metabolic syndrome. The morbidity of cardiovascular diseases is expected to increase synergistically by clustering of them. In the present study, we assessed the clustering of cardiovascular risk factors and blood pressure (BP) control status in hypertensive patients. METHODS AND PATIENTS: Subjects were 699 treated hypertensive patients (mean age: 65 +/- 12 years; males 297, females 402) who had been followed at National Kyushu Medical Center, Fukuoka, Japan. We assessed the status of BP control and the presence of comorbidity including obesity, diabetes mellitus (DM), dyslipidemia, CKD and hyperuricemia. RESULTS: Average BP level and the number of antihypertensive drugs were 133 +/- 11/74 +/- 10 mmHg and 2.0 +/- 1.1, respectively and the average number of cardiovascular risk factors was 1.5 +/- 1.1. No comorbid risk factors were found in 18.7% of the patients. On the other hand, 34.2%, 28.9% and 18.2% of the patients had one, two or more than three risk factors, respectively. There were no significant differences in BP among these groups, while patients with three or more risk factors needed a greater number of antihypertensive drugs than those with other groups. Patients with three or more risk factors group showed significantly higher body mass index, serum LDL cholesterol, triglyceride, plasma glucose and serum uric acid levels compared to those with other groups (p<0.05, respectively). They also showed significantly lower serum HDL cholesterol and estimated GFR levels compared to those in other groups (p<0.05, respectively). CONCLUSION: These results suggest that the majority of the treated hypertensive patients are complicated with additional cardiovascular risk factors and the patients with clustering risk factors required a greater number of antihypertensive drugs. Integrative management of BP as well as comorbid risk factors should be encouraged.

Long-term compliance of salt restriction and blood pressure control status in hypertensive outpatients.

The purpose of the present study was to investigate the long-term compliance with salt restriction and blood pressure (BP) control status in Japanese hypertensive outpatients. Subjects included 103 patients, 59 women and 44 men, mean age 67 +/- 9 years, who underwent successful 24-h home urine collection more than 10 times over an interval of 5 years. Urinary salt, potassium, and creatinine were measured. During the follow-up period (average 8.6 years), participants underwent urine collection 11.4 times in average. Urinary salt excretion at the last visit was significantly lower than that of the first visit (8.2 +/- 3.1 vs. 9.6 +/- 3.7 g/day; p < 0.01). The achievement of urinary salt excretion <6 g/day increased from 18.5% at the first visit to 26.2% at the last visit. Similarly, BP at the last visit was significantly lower than that of the first visit (130 +/- 14/69 +/- 11 vs. 145 +/- 17/86 +/- 12 mmHg; p < 0.01). The achievement rate of BP <140/90 mmHg and <130/85 mmHg also increased significantly during this period (39.2% to 70.8% and 13.7% to 39.6%, respectively, p < 0.01). Results suggest that urinary salt excretion decreased by repeated measurements using 24-h home urine collection. Lifestyle modification including weight loss as well as the intensive antihypertensive treatment contributed to the improved BP control during this period.

Usefulness of self-monitoring of urinary salt excretion in hypertensive patients.

We investigated the usefulness of measuring urinary salt excretion by using a self-monitoring device. Subjects were 34 hypertensive patients who underwent successful 24-h home urine collection five times and 25 volunteers. Four volunteers were diagnosed as having hypertension based on home blood pressure (BP) readings. All subjects were asked to measure daily urinary salt excretion for 30 days by using a self-monitoring device which estimates 24-h salt excretion by overnight urine. The mean urinary salt excretion during the 30 days was 8.36 +/- 1.52 g/day and the range (maximum-minimum value) was 5.47 +/- 20.05 g/day in all subjects. Mean urinary salt excretion decreased from 8.52 +/- 1.63 g/day for the first 10 days to 8.31 +/- 1.54 g/day for the last 10 days (p < 0.05). The mean urinary salt excretion determined by a self-monitoring device using overnight urine was positively associated with that determined by 24-h home urine for five times in the hypertensive subjects (r = 0.63, p < 0.01). Results indicate that a self-monitoring device seems to be useful to monitor daily salt intake and to guide salt restriction.

Blood pressure and lipid control status in Japanese hypertensive patients.

Strict blood pressure (BP) as well as lipid control is important to prevent cardiovascular events. The purpose of this study was to evaluate BP and lipid control status in hypertensive patients. Subjects were a total of 717 hypertensive patients who had been followed at National Kyushu Medical Center in FuKuoka, Japan. Goal BP was defined as < 130/85 mmHg (< 65 years) or < 140/90 mmHg (> or = 65 years). According to the Japanese guidelines, goal LDL cholesterol (LDL-C) levels were defined based on the patient category. Average BP level and the number of anti-hypertensive drugs were 133 + or - 12/74 + or - 9 mmHg and 2.1 + or - 1.1, respectively, and the LDL-C level was 119 + or - 27 mg/dl. Goal BP was achieved in 40% of the patients of < 65 years and 67% of the elderly patients. Goal LDL-C was achieved in 65% of the patients. Even in the patients taking lipid-lowering agents (n = 178), 30% failed to achieve goal LDL-C levels. In the patients who achieved BP < 130/85 mmHg, 67% also achieved goal LDL-C, whereas 61% of the patients whose BP > or = 140/90 mmHg achieved goal LDL-C. Both goal BP and LDL-C were achieved in 39% of the male and 36% of the female patients. In contrast, neither goal BP nor goal LDL-C was achieved in 16% of the male and 17% of the female patients. Results suggest that intensive intervention should be required to achieve satisfactory BP and lipid control in hypertensive patients.

Home blood pressure measurement may lead to less strict control of office blood pressure.

Home blood pressure (HBP) measurement is useful for detecting morning hypertension, white coat as well as masked hypertension. However, target BP levels based on HBP remain unknown. The purpose of the present study was to evaluate the relationship between HBP measurement and office BP control status in hypertensive patients. Subjects were a total of 720 hypertensive outpatients (mean age: 64 +/- 11 years; females: 57%). Two-time averaged office BP in 2005 were categorized as excellent (<130/85 mmHg), good (> or =130/85 and <140/90 mmHg), or poor (>140/90 mmHg) control. In all patients, 37% were classified as excellent, 37% as good, and 26% as poor control. A total of 393 (55%) patients regularly measured HBP (HBP group). More women belonged to the HBP group (62 vs. 52%, p < 0.05). The HBP group also showed lower body mass index (23.8 +/- 3.3 vs. 24.7 +/- 3.4 kg/m(2), p < 0.01), lower triglyceride (136 +/- 78 vs. 158 +/- 89 mg/dl, p < 0.01), and lower blood glucose (104 +/- 20 vs. 118 +/- 42 mg/dl, p < 0.01). HBP group showed a significantly higher prevalence of poor BP control (33 vs. 23%, p <0.01) and higher office SBP (134.5 +/- 14.5 vs. 131.3 +/- 11.7 mmHg, p < 0.01) than those who did not measure HBP (non-HBP). In a multivariate analysis for office SBP, age (partial r = 0.21, p < 0.05) and HBP measurement (partial r = 0.12, p < 0.05) were detected as significant independent variables. These results suggest that HBP measurement may lead to less strict office BP control unless the target HBP levels are clearly indicated. Until the recommendations or target HBP levels are available, we should make an effort to obtain goal office BP.

Usefulness of the alpha1-blocker doxazosin as a third-line antihypertensive drug.

It has been reported that a substantial majority of hypertensives receive insufficient blood pressure (BP) control. As combination therapy for the treatment of hypertension, Ca channel blockers (CCBs), angiotensin II (AII) receptor blockers (ARBs), and/or AII-converting enzyme (ACE) inhibitors are mainly prescribed, while the efficacy of alpha(1)-blockers in such combination therapy remains unknown. The aim of this study was to investigate the efficacy of a low dose of an alpha(1)-blocker added to combination therapy with CCBs and either ARBs or ACE inhibitors for the treatment of hypertension. Subjects were 41 hypertensive patients (23 women and 18 men, mean age 66+/-12 years) who had been followed at the National Kyushu Medical Center. All patients showed poor BP control despite haven taken a combination of CCBs and ARBs or ACE inhibitors for more than 3 months. Doxazosin at a dose of 1 to 2 mg was added to each treatment regimen. The changes in various clinical parameters, including BP and blood chemistry, following the addition of doxazosin were then evaluated. The mean follow-up period was 170 days. BP decreased from 152+/-14/81+/-12 mmHg to 135+/-14/70+/-11 mmHg after the addition of doxazosin at a mean dose of 1.5 mg/day (p<0.001). When good systolic blood pressure (SBP) control was defined as <140 mmHg, the prevalence of patients with good SBP control increased from 24% to 61% (p<0.01). Similarly, the prevalence of patients with good diastolic blood pressure (DBP) control (<90 mmHg) increased from 78% to 98% (p<0.01). Patients whose SBP decreased more than 10 mmHg (n=25) showed significantly higher baseline SBP, serum total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to those who showed less SBP reduction (<10 mmHg) (n=16, p<0.01). Comparable BP reductions were obtained between obese (body mass index [BMI] > or =25, DeltaBP at 3 months: -15+/-15/-12+/-9 mmHg, n=18) and non-obese (BMI<25, DeltaBP: -14+/-19/-7+/-8 mmHg, n=23) patients. The results suggest that addition of a low dose of the alpha(1)-blocker doxazosin effectively reduces BP in patients taking CCBs and ARBs or ACE inhibitors. Thus, doxazosin seems to be useful as a third-line antihypertensive drug.

Prevalence and lifestyle characteristics of hypertensive patients with metabolic syndrome followed at an outpatient clinic in fukuoka, Japan.

A new guideline on metabolic syndrome (MS) in Japanese was introduced in 2005. The purpose of this study was to evaluate the prevalence and lifestyle characteristics of Japanese hypertensive patients with MS. Subjects were 290 patients (mean age: 64+/-11 years) who had been followed at our hospital. The waist circumference (WC) and body mass index (BMI) were assessed. Subjects who had BMI >or=25 kg/m(2) were defined as having BMI obesity, while abdominal obesity was defined as a WC >or=85 cm in men and >or=90 cm in women, respectively. Since all patients had hypertension, the definition of MS was made when the patient had abdominal obesity plus either dyslipidemia or glucose intolerance, or both. Among the subjects, 230 patients underwent 24-h home urine collection to measure urinary salt and potassium excretions. Dietary habits were also assessed by use of a questionnaire. Mean values of BMI and WC were 24.2+/-3.4 kg/m(2) and 87.1+/-9.6 cm, respectively. Among the total subject group, 39% patients were classified as having BMI obesity, 49% as having abdominal obesity, and 27% as having MS. BMI was significantly correlated with WC both in men (r=0.86; p<0.01) and in women (r=0.79; p<0.01). More men than women belonged to the BMI obesity (46% vs. 33%, p<0.05), abdominal obesity (63% vs. 39%, p<0.01) and MS (39% vs. 18%, p<0.01) groups. There were no significant differences in blood pressure between patients with and without MS, while patients with MS needed a greater number of antihypertensive drugs than those without MS. Mean urinary salt and potassium excretions were 8.9+/-3.8 g/day and 1.9+/-0.7 g/day, respectively. Urinary salt excretion of <6 g (100 mmol of sodium)/day was achieved in 20% of the subjects. Urinary salt excretion in the patients with MS was significantly higher than that in the patients without (10.1+/-4.2 vs. 8.5+/-3.6 g/day; p<0.01). Only 16% of the patients with MS achieved salt restriction (<6 g/day). The patients with MS had a significantly greater the chance to eat out than the patients without MS. They were also less aware of the need to increase their vegetable consumption. The results suggested that MS is prevalent in Japanese hypertensive patients. Patients with MS showed higher urinary salt excretion and needed more antihypertensive drugs to manage their blood pressure. Dietary counseling focusing not only on sodium restriction but also on the need to increase fruit and vegetable consumption seems to be important.

A case of Gitelman's syndrome with decreased angiotensin II-forming activity.

Gitelman's syndrome (GS) is a variant of Bartter's syndrome (BS) characterized by hypokalemic alkalosis, hypomagnesemia, hypocalciuria and secondary aldosteronism without hypertension. A 31-year-old Japanese man who had suffered from mild hypokalemia for 10 years was admitted to our hospital. He had metabolic alkalosis, hypokalemia and hypocalciuria. Since he had two missense mutations (R261C and L623P) in the thiazide-sensitive Na-Cl cotransporter (TSC) gene (SLC12A3), he was diagnosed as having GS. He showed hyperreninism and a high angiotensin I (Ang I) level, whereas his angiotensin II (Ang II) and aldosterone levels were not elevated. His angiotensin converting enzyme (ACE) activities were normal, and administration of captopril inhibited the production of Ang II and aldosterone. We evaluated the Ang II-forming activity (AIIFA) of other enzymes in his lymphocytes. Interestingly, chymase-dependent AIIFA was not detected in the lymphocytes. Together, these results suggest that the lack of chymase activity resulted in the manifestation of GS without hyperaldosteronism.

Anti-proteinuric effect of an N-type calcium channel blocker, cilnidipine.

The objective of the present study was to determine anti-proteinuric effect of an N-type calcium channel blocker-cilnidipine. Subjects were 43 essential or renal hypertensive subjects who had been taking calcium channel blockers other than cilnidipine for at least 6 months. All patients had proteinuria greater than 0.2 g/day in spite of fair blood pressure control (<150/90 mmHg). Calcium channel blockers in 25 patients (62+/-3 years) were switched to cilnidipine (cilnidipine group), whereas other 18 patients (58+/-3 years) continued to take originally prescribed calcium channel blockers (control group). The 24-hr urine collections were done at baseline and after 6 months of the follow-up period. Baseline characteristics including age, blood pressure levels, body mass index and creatinine clearance were similar between cilnidipine and control groups. Urinary protein excretion also was comparable between cilnidipine (0.61+/-0.10 g/day) and control (0.86+/-0.17 g/day) groups. Urinary protein significantly decreased after 6 months in cilnidipine group (- 0.21+/- 0.11 g/day, - 36%, p< 0.01), whereas it did not change in control group (+ 0.01+/- 0.15 g/day, 0.4%, ns). There were no significant changes in blood pressure, serum creatinine, creatinine clearance, estimated protein intake, and urinary salt excretion during the follow-up period in either group. The reduction of urinary protein by cilnidipine was evident in essential hypertensives (- 54+/-9%, n=18, p<0.01) but not in renal hypertensives (+10+/-35%, n=7, ns). Results suggest that cilnidipine has an anti-proteinuric effect especially in patients with essential hypertension.

Long-term compliance with salt restriction in Japanese hypertensive patients.

The purpose of the present study was to investigate the long-term compliance with salt restriction in Japanese hypertensive patients. Subjects included 389 patients, 230 women and 159 men, mean age 58+/-11 years, who underwent successful 24-h home urine collection more than three times over an interval of a year. Urinary salt, potassium, and creatinine were measured. Additionally, family history, habitual alcohol intake, smoking habit, physical activities, and job status were assessed by use of a questionnaire. During the follow-up period (average 3.5 years), participants underwent urine collection 4.6 times in average. Urinary salt excretion at the last visit was significantly lower than that at the first visit (8.7+/-3.4 vs. 9.6+/-4.1 g/day; p<0.01). Urinary potassium excretion also decreased significantly during this period (from 2.0+/-0.7 to 1.9+/-0.7 g/day; p<0.05). Among the mean 4.6 urine collections, 45.2% (men 34.6%, women 52.6%) of the patients successfully achieved <6 g (100 mmol of sodium)/day of salt excretion on at least one occasion. The rate of achievement of averaged urinary salt excretion <6 g/day dropped to 10.3% (men 4.4%, women 14.3%). Only 2.3% (men 0.6%, women 3.5%) of the patients achieved <6 g/day on all occasions. There were no significant differences in age, habitual alcohol intake, smoking habit, physical activities, or job status between patients who complied with the salt-restricted diet and those who did not. Results suggest that long-term compliance with salt restriction is poor in Japanese hypertensive patients. Since no specifically defining characteristics were found in the compliant patients, repeated measurements of urinary salt excretion seem to be important to encourage salt restriction.

Relationship between the awareness of salt restriction and the actual salt intake in hypertensive patients.

A 24-h home urine collection was conducted to estimate accurate salt intake in hypertensive outpatients. Using 24-h urinary creatinine excretion as a criterion for success, urine samples were obtained from 534 hypertensive patients. The urinary salt excretion of hypertensive outpatients ranged widely from 1.5 to 23.4 g/day (mean value 9.7 +/- 3.9 g/day). Urinary salt excretion was higher in males than in females (10.6 +/- 4.0 vs. 9.2 +/- 3.7 g/day, p<0.01). Based on the questionnaires, the patients were divided into salt-conscious patients, or those who were careful to reduce their daily salt intake, and non-salt-conscious patients. It was found that urinary salt excretion was lower in the salt-conscious group than in the non-salt-conscious group (9.4 +/- 3.8 vs. 10.6 +/- 4.0 g/day, p<0.01), but that urinary salt excretion adjusted for body weight was not significantly different between the two groups (0.16 +/- 0.06 vs. 0.17 +/- 0.07 g/kg/day). Our results suggest that there was no obvious reduction in the actual salt intake in salt-conscious patients, suggesting the importance of monitoring salt intake by 24-h home urine collection and informing patients of their actual salt intake as a means of encouraging the achievement of salt restriction.