C-reactive protein and incident hypertension in a worksite population of Japanese men.

Inflammation plays a key role in the pathogenesis of cardiovascular diseases via the development of atherosclerosis. Here, we evaluated the impact of serum C-reactive protein (CRP) and the white blood cell (WBC) count on the risk of hypertension in middle-aged Japanese men at a work site. We evaluated a total of 2991 Japanese male workers without hypertension who ranged in age from 18 to 64 years (mean age 40.4 ± 0.2 years) at a worksite in 2010. The hazard ratio (HR) for incident hypertension was estimated according to quartile levels of serum high-sensitivity CRP (hs-CRP) or WBC count. These men were followed up for 5 years from 2010 to 2015. During the follow-up period, 579 (19.4%) subjects developed hypertension. In a multivariable analysis, the risk of incident hypertension was significantly increased with higher hs-CRP levels: HR 1.00 (reference) for the lowest quartile, 1.39 (1.04-1.85) for the 2nd quartile, 1.46 (1.08-1.98) for the 3rd quartile, and 1.57 (1.17-2.11) for the highest quartile. In contrast, the WBC count was not associated with a greater risk of incident hypertension after multivariable adjustment. These findings suggest that higher levels of serum hs-CRP, but not the WBC count, are associated with the future incidence of hypertension in middle-aged Japanese men.

Impact of serum uric acid on incident hypertension in a worksite population of Japanese men.

OBJECTIVE: Higher levels of serum uric acid are associated with an increased risk of cardiovascular diseases, which may be confounded by comorbidities. We investigated the effects of serum uric acid on the risk of hypertension in Japanese men at a worksite. METHODS: We evaluated a total of 2335 Japanese male workers without hypertension who ranged in age from 18 to 64 years at a worksite in 2009. These men were followed for 6 years from 2009 to 2015. RESULTS: During the follow-up period, 380 individuals developed hypertension. The odds ratio for the incident hypertension was estimated according to quartiles of serum uric acid levels of 5.1 or less, 5.2-5.8, 5.9-6.6, and at least 6.7 mg/dl. The multivariable-adjusted risk of incident hypertension was significantly higher in the highest serum uric acid quartile than in the lowest: odds ratio 1.00 (reference) for the lowest quartile, 1.34 (0.91-1.97) for the second quartile, 1.42 (0.97-2.06) for the third quartile, and 1.65 (1.14-2.40) for the highest quartile. In stratified analyses, the association between serum uric acid and incident hypertension was significant in the patients of aged below 45 years and without comorbidities, namely diabetes and low levels of high-density lipoprotein-cholesterol. CONCLUSIONS: Serum uric acid levels were associated with the future incidence of hypertension, and the association was observed in the younger individuals, those without diabetes, and those with preserved high-density lipoprotein cholesterol levels in a worksite population of Japanese men.

Downregulation of Endothelial Transient Receptor Potential Vanilloid Type 4 Channel and Small-Conductance of Ca2+-Activated K+ Channels Underpins Impaired Endothelium-Dependent Hyperpolarization in Hypertension.

Endothelium-dependent hyperpolarization (EDH)-mediated responses are impaired in hypertension, but the underlying mechanisms have not yet been determined. The activation of small- and intermediate-conductance of Ca2+-activated K+ channels (SKCa and IKCa) underpins EDH-mediated responses. It was recently reported that Ca2+ influx through endothelial transient receptor potential vanilloid type 4 channel (TRPV4) is a prerequisite for the activation of SKCa/IKCa in endothelial cells in specific beds. Here, we attempted to determine whether the impairment of EDH in hypertension is attributable to the dysfunction of TRPV4 and S/IKCa, using isolated superior mesenteric arteries of 20-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and age-matched Wistar-Kyoto (WKY) rats. In the WKY arteries, EDH-mediated responses were reduced by a combination of SKCa/IKCa blockers (apamin plus TRAM-34; 1-[(2-chlorophenyl)diphenylmethl]-1H-pyrazole) and by the blockade of TRPV4 with the selective antagonist RN-1734 or HC-067047. In the SHRSP arteries, EDH-mediated hyperpolarization and relaxation were significantly impaired when compared with WKY. GSK1016790A, a selective TRPV4 activator, evoked robust hyperpolarization and relaxation in WKY arteries. In contrast, in SHRSP arteries, the GSK1016790A-evoked hyperpolarization was small and relaxation was absent. Hyperpolarization and relaxation to cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, a selective SKCa activator, were marginally decreased in SHRSP arteries compared with WKY arteries. The expression of endothelial TRPV4 and SKCa protein was significantly decreased in the SHRSP mesenteric arteries compared with those of WKY, whereas function and expression of IKCa were preserved in SHRSP arteries. These findings suggest that EDH-mediated responses are impaired in superior mesenteric arteries of SHRSP because of a reduction in both TRPV4 and SKCa input to EDH.

Increased uric acid promotes decline of the renal function in hypertensive patients: a 10-year observational study.

OBJECTIVE: Uric acid (UA) has shown to be a causal risk factor for the development and progression of renal disease. The aim of this study was to investigate the relationship between changes in the level of UA and trends in the renal function among hypertensive patients during a 10-year observation period. METHODS: The subjects included 104 hypertensive outpatients (60 women and 44 men, mean age 60±9 (SD) years at the first visit) who had undergone at least five instances of successful 24-hour home urine collection, with the first examination completed between 1998 and 2000 and the last examination completed between 2008 and 2010. RESULTS: The estimated glomerular filtration rate (eGFR) significantly decreased over the 10.4-year observation period, with an average change in eGFR of -0.66/mL/min/year. The uric acid clearance at the last examination was significantly lower than that observed at the first visit, while there were no significant differences in the serum UA levels during this period. The change in serum UA exhibited a significant negative correlation with the change in eGFR (r=-0.34, p<0.01). The patients whose UA level decreased more than 0.5 mg/dL during the observation period demonstrated significantly smaller declines in eGFR compared to those whose UA level increased more than 0.5 mg/dL. In the multivariate analysis, the change in serum UA and the average urinary salt excretion during the observation period were found to be significantly associated with the change in eGFR, independent of age, sex, BP changes or an increased number of antihypertensive drugs. CONCLUSION: Based on the findings observed over a 10-year observation period, increased UA is suggested to promote decline of the renal function in hypertensive patients. Controlling the level of UA as well as intensively restricting salt intake is required in order to preserve the renal function.

Perioperative blood pressure variability in the treated hypertensive patients.

Perioperative blood pressure (BP) management is important to prevent cardiovascular complication, especially for hypertensive patients. In the present study, we investigated perioperative BP variability and contributing factors in hypertensive patients. Subjects were 28 treated hypertensive patients who underwent total or subtotal gastrectomy. Ambulatory BP monitoring was carried out before and after (16 days in average) the surgery. Angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and diuretics were withdrawn on the previous day, while other drugs were administered until the day of surgery. BP, body weight, blood chemistry, as well as the use of intravenous vasopressor or vasodepressor agents during the perioperative period were investigated. The 24-hour BP before surgery was 124 ± 19/70 ± 12 mm Hg, and the number of antihypertensive drugs was 1.8. In 22 patients, intravenous vasopressor agents were used during surgery, while another patient received intravenous vasodepressor agents after surgery. The 24-hour BP significantly decreased after surgery (-8.2 ± 14.7/-2.6 ± 7.3 mm Hg). Body weight, serum Na, and hematocrit also decreased. There were nine patients whose 24-hour systolic BP decreased by more than 10 mm Hg and for two patients more than 20 mm Hg. The decrease in BP correlated with the change in serum Na. Forty-three percent of the patients who took ACE inhibitors/ARBs showed BP reduction greater than 10 mm Hg, while 25% of the patients without these drugs showed such BP reduction. Our findings suggest that 24-hour BP decreases after gastrectomy. Patients taking ACE inhibitors or ARBs may need careful monitoring to prevent excessive BP fall.

High salt intake promotes a decline in renal function in hypertensive patients: a 10-year observational study.

We investigated the influence of long-term salt load on renal function in hypertensive patients. The subjects were 133 hypertensive patients (80 women and 53 men, mean age 60±9 years) who underwent at least five successful 24 h home urine collections during the 10-year observation period. Blood pressure (BP) and 24-h urinary salt and creatinine excretion levels were measured. BP decreased from 143±12/85±8 to 129±14/68±11 mm Hg during the 10.5-year observation period, and this decrease was associated with patients taking an increased number of antihypertensive drugs (1.3±1.0 to 2.2±1.1). The estimated glomerular filtration rate (eGFR) also significantly decreased from 71.7±14.6 to 64.7±16.5 ml min(-1) (P<0.01), and the change in eGFR was -0.68 ml min(-1) per year on average. The average salt excretion was 8.6±2.2 g per day and showed a significant negative correlation with the change in eGFR (r=-0.21, P=0.02). Subjects with an average salt excretion<8 g per day showed a significantly slower decline in renal function than those with an average salt excretion 8 g per day (the change in eGFR: -0.41±1.10 vs. -0.83±1.19 ml min(-1) per year, P<0.05). In the multivariate analysis, the average salt excretion (partial r=-0.19, P=0.03) and baseline eGFR (partial r=-0.23, P=0.01) were significantly associated with the change in eGFR. This association was independent of BP change or an increased number of antihypertensive drugs. The results suggest that long-term salt load promotes a decline in renal function in hypertensive patients; thus, salt restriction is encouraged, to prevent renal damage.

Influence of salt intake on target organ damages in treated hypertensive patients.

This study investigates the influence of salt intake on renin-angiotensin-aldosterone system and clarifies their role to the target organ damage in the treated hypertensive patients. Subjects were 188 treated hypertensive outpatients (96 females and 92 males, mean age 67 ± 11 y). Patients underwent 24-hour home urine collection to measure urinary salt excretion and proteinuria. Clinical blood pressure (BP) and blood chemistry including plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined. Left ventricular mass index (LVMI) was also determined by echocardiography. Average BP was 129 ± 16/68 ± 10 mm Hg with the use of 2.0 antihypertensive drugs on average. Urinary salt excretion, PRA, and PAC were 8.1 ± 3.2 g/day, 2.2 ± 2.8 ng/mL/h, and 112 ± 54 pg/mL, respectively. Even in the patients taking angiotensin receptor blocker or angiotensin-converting enzyme inhibitors (n = 146), 15.1% showed low PRA (<0.5 ng/mL/h) levels and salt excretion in these patients with low PRA (9.1 ± 4.2 g/day) did not differ from those with higher PRA levels (8.2 ± 2.6 g/day, NS). There was no correlation between salt excretion and PRA (r = 0.03, NS), while salt excretion showed a significant negative correlation to PAC (r = -0.17, P < .05). Urinary salt excretion was also correlated with proteinuria (r = 0.25, P < .01) and LVMI (r = 0.16, P < .05). In the multivariate analysis, salt excretion contributed to proteinuria (P < .05) or LVMI (P = .11) independent of age, sex, serum creatinine, and BP levels. Results indicate that PRA levels were relatively low and unaffected by salt intake in Japanese patients treated with antihypertensive drugs. Since high salt intake was possibly associated with target organ damages, strict salt reduction should be encouraged.

Trend of blood pressure control status in hypertensive outpatients: with special reference to elderly hypertensives.

Blood pressure (BP) control in hypertensives has improved; however, it still remains to be insufficient. We have investigated the trend in BP control status of the hypertensive patients followed for 10 years in hypertension clinic. Subjects included 133 patients who have been followed from the first visit during 1998-2000 to the last visit during 2008-2010. During the mean follow-up period of 10.5 years, average BP and body weight significantly (P < .01) decreased from 143 ± 12/85 ± 8 mm Hg to 129 ± 14/68 ± 11 mm Hg, and from 59.8 ± 9.9 kg to 58.7 ± 10.6 kg, respectively. The achievement rate of good BP control defined as <140/90 mm Hg and the number of antihypertensive drugs also increased significantly during this period (39.1%-77.5% and 1.3 ± 1.0-2.2 ± 1.1, respectively, P < .01). Blood pressure control improved and the number of antihypertensive drugs also increased in 45 patients who were older than 65 years at the last visit. The use of Ca channel blockers (CCBs), angiotensin II receptor antagonists, and diuretics increased significantly during this period. Results suggest that lifestyle modification including body weight reduction as well as intensive antihypertensive treatment contributed to the improved BP control in hypertensive patients including the elderly.

Relationship between blood pressure control status and lifestyle in hypertensive outpatients.

OBJECTIVE: Lifestyle modification as well as combination antihypertensive therapy is necessary to achieve strict blood pressure (BP) control as advocated by the guidelines for the treatment of hypertension. The aim of this study was to investigate the status of adherence to lifestyle modifications and BP control status in hypertensive outpatients. METHODS AND PATIENTS: Subjects are 661 hypertensive outpatients who had been followed at National Kyushu Medical Center. We assessed BP control status based on the average clinic BP on two occasions. In addition, we investigated the adherence to the individual items of lifestyle modification by a questionnaire. RESULTS: Average BP was 129 ± 10/71 ± 11 mmHg and overall rate of achieving goal BP was 60.1%. Achieving rate of each target BP category was 83.3% in the elderly patients (<140/90 mmHg), 56.7% in the young/middle patients (<130/85 mmHg) and 45.5% in the patients with diabetes mellitus/chronic kidney disease/myocardial infarction (<130/80 mmHg). Adherance to each item of lifestyle modification was as follows: Patients who answered to be conscious about salt restriction was 80.9%, those with increased intake of fruits/vegetables was 79.0%, reduced intake of cholesterol/saturated fatty acids was 67.9%, presence of obesity was 37.7%, daily exercise for ≥30 min was 31.9%, habitual alcohol intake was 38.0%, habitual smoking was 9.8%. Only 22.5% of the patients had no lifestyle items to be modified. On the other hand, 19.6% of patients had more than 3 items to be modified. Subjects with more than 3 lifestyle items to be modified are more frequently found in young, male, and obese groups. CONCLUSION: We conclude that about 60% of the patients achieved goal BP by the intensive combination therapy. The lifestyle modification seems to be important especially for the young, male and obese patients.

Consequence of masked hypertension in treated hypertensive outpatients: 1-year follow-up study.

Since masked hypertension (MHT) is high risk for cardiovascular disease, the importance of home blood pressure (HBP) control is emphasized. The aim of this study was to investigate the prevalence of MHT in the treated hypertensives and the consequence of their BP control status after a 1-year follow up period. Subjects are 262 treated hypertensive outpatients. We assessed BP control status, background characteristics, and antihypertensive drugs in both 2008 and 2009. Clinic BP (CBP) and morning HBP in 2008 were 133 ± 12/73 ± 9 mmHg and 132 ± 11/77 ± 8 mmHg, which significantly decreased to 129 ± 11/70 ± 10 mmHg and 130 ± 10/76 ± 8 mmHg in 2009, respectively (p < 0.01). The patients with sustained hypertension (SHT) decreased from 17.9% in 2008 to 6.9% in 2009. Thirty-four percent of SHT patients in 2008 turned out to be MHT and another 34.0% belonged to normotension (NT) in 2009. Among 79 MHT patients in 2008, 62.0% remained as MHT, while 32.9% turned out to be NT in 2009. The sustained MHT patients were more male and showed a higher prevalence of habitual alcohol intake. Nighttime dosing of antihypertensive drugs and the addition of diuretics were major causes of improving morning HBP. Results suggest that one-third of MHT patients showed the improvement of HBP after the 1-year follow-up period. Not only intensive antihypertensive treatment with the appropriate use of diuretics, but also the encouragement of lifestyle modification including alcohol restriction, seems to be important to the management of MHT.