Analysis of Factors Relating to Day-to-day Home Blood Pressure Variation in Hypertensive Patients

　In order to prevent cardiovascular events and organ injuries in hypertensive patients, strict blood pressure（BP）control over 24 hours is of utmost importance. In addition to the BP level, it has been indicatedthat the variabilities of blood pressure during a day or between visits also influence the risk of cardiovascular disorders. This study aimed to delineate the factors relating to the variations of office and home BPs throughout a year in hypertensive outpatients under antihypertensive therapy. The office BP value（131/77 mmHg）was comparable to the morning home BP（130/76）, but was higher compared to the evening home BP（126/73）, however, the coefficient of variation（CV）values were comparable between the office and the home BPs. Correlations of BP and CV were stronger between the morning and the evening home BPs than between the office and the home BPs. The CV of systolic office BP was greater in patients with diabetes mellitus than the patients without diabetes（7.8 vs 6.1％）. In patients with chronic kidney disease, the CVs of diastolic office BP and evening home BP were greater than the patients without chronic kidney disease（8.0 vs 6.2％ and 8.1 vs 6.7％, respectively）. In addition, The CVs of diastolic morning and evening home BP were positively correlated with serum creatinine and a negatively correlated with estimated glomerular filtration rate. Patients with cardiovascular diseases such as stroke and coronary artery disease showed greater CV of diastolic morning home BP than the patients without cardiovascular diseases（8.2 vs 6.6％）. These results suggest that the home BP exhibits different variability from the office BP, and the BP variability is increased in high-risk hypertensive patients with diabetes mellitus, chronic kidney disease or cardiovascular diseases

Therapeutic Effects of a Sodium Glucose Cotransporter 2 Inhibitor in Diabetic Patients with Chronic Kidney Disease

Multiple large-scale clinical trials have indicated that sodium glucose cotransporter 2（SGLT2）inhibitors reduce the incidence of cardiovascular events, deterioration of renal function and mortality. However, the therapeutic effects of SGLT2 inhibitors are supposed to be limited in patients with reduced renal function considering the mechanism of their action. In this study, a SGLT2 inhibitor, ipragliflozin was given to 30 type 2 diabetic patients with nephropathy whose estimated glomerular filtration rate（eGFR）was not lower than 30 mL/min/1.73 m2. After 12 to 16 weeks, hemoglobin A1c decreased by 0.6％（p＜0.001）, body weight was reduced by 1.8 kg（p＜0.01）and blood pressure was lowered by －10/－6 mmHg（p＜0.001/p ＜0.001）. This was accompanied by reductions in serum uric acid（－0.7 mg/dL, p＜0.001）, triglycerides （－25 mg/dL, p＝0.028）and g-glutamyl transferase（－8 U/L, p＝0.001）. On the other hand, plasma B-type natriuretic peptide also decreased by 12％（p＝0.020）and urinary albumin excretion was reduced by 23％ （p＝0.018）although the eGFR was not significantly changed. It is concluded that ipragliflozin is effective in lowering blood glucose even in patients with diabetic kidney disease and is beneficial in improving theaccompanying obesity and hypertension. In addition, ipragliflozin is thought to have favorable influences on the metabolisms of uric acid and lipids. These properties of ipragliflozin is expected to bring about protective effects against the progression of nephropathy and the development of cardiovascular disease resulting in the improvement of prognosis in diabetic patients with mild to moderate chronic kidney disease

Comparisons of Therapeutic Effects of Allopurinol and Febuxostat in Chronic Hemodialysis Patients

More than few patients on maintenance hemodialysis present with hyperuricemia, and the control of serum uric acid level is an important issue in the long-term management. In addition to allopurinol, febuxostat can be used as a xanthine oxidase inhibitor in hemodialysis patients. In this study, the clinical effects of febuxostat were compared with allopurinol in chronic hemodialysis patients. Eligible hemodialysis patients taking allopurinol were randomly assigned to take 100 mg allopurinol（n＝26）or 20 mg febuxostat（n＝23）for 12 weeks. Serum uric acid was markedly lowered in the febuxostat group（0-week 6.7 mg/dL, 12-week 4.3 mg/dL, p＜0.001）as compared with the allopurinol group（0-week 6.0 mg/dL, 12-week 5.8 mg/dL）and systolic blood pressure was lowered by 5 mmHg（p＝0.036）at 4-week in the febuxostat group while blood pressure was not significantly changed in the allopurinol group throughout the study period. In addition, the dose of erythropoiesis stimulating agent was reduced（0-week 22.2 μg/wk, 12-week, 17.1 μg/wk, p＝0.012）and serum phosphate level was lowered（0-week 5.9 mg/dL, 12-week 5.1 mg/dL, p＝0.027）in the febuxostat group but not in the allopurinol group. It is concluded that febuxostat is more effective in lowering serum uric acid than allopurinol in hemodialysis patients. In addition, it is suggested that febuxostat has an advantage in the management of renal anemia and hyperphosphatemia as well as hyperuricemia

Comparisons of Increasing Calcium Channel Blocker dose and Adding Thiazide Diuretic in Hypertensive Patients Given Medium-dose Angiotensin II Receptor Blocker and Amlodipine

We compared the efficacies of 2 prescriptions, one of a medium-dose angiotensin II receptor blocker （ARB） with high-dose of calcium channel blocker （CCB） and another of medium-dose of ARB with medium-dose of CCB and a thiazide diuretic in 22 hypertensive patients who did not achieve the target blood pressure level with the combination of medium-dose of ARB and medium-dose of CCB. A randomized crossover study was performed giving a fixed combination of 100 mg irbesartan with 10 mg amlodipine or a fixed-dose combination of 100 mg irbesartan with 5 mg amlodipine added by 1 mg trichlormethiazide for 12-16 weeks each. The blood pressure measured in hospital was comparable between the high-dose CCB period （130/77 mmHg） and the thiazide period （130/79 mmHg）. The morning and the evening blood pressures measured at home were also comparable in the high-dose of CCB and the thiazide periods, while the evening heart rate was higher in the thiazide period than in the high-dose CCB period. As for the laboratory data, hemoglobin A1c （＋0.2％, p＝0.013）, serum nonHDL cholesterol （＋12 mg/dL, p＝0.047） and serum uric acid （＋0.8 mg/dL, p＝0.001） were significantly higher in the thiazide period than in the high-dose CCB period. On the other hand, urinary albumin excretion （－28.8％，p＝0.026） and estimated glomerular filtration rate （－5.8％，p＝0.012） were significantly lower in the thiazide period than in the high-dose CCB period. In the combination drug therapy of hypertension, the increase of CCB dose is preferable in preserving renal function and in avoiding adverse effects on metabolisms of glucose, lipid and uric acid

セイカツ シュウカン ノ シュウセイ ニヨル コウケツアツ ノ ヨクセイ

高血圧の抑制を目的とした生活習慣の修正について多角的に概説した.すなわち,食塩,カリウム,カルシウム,マグネシウム,脂質,食物繊維などの栄養因子,肥満,運動,ストレス,そして飲酒,喫煙,コーヒーなどの嗜好品を取り上げた.今後,予防医学的な意味で,生活習慣の修正により,各種の循環器疾患において主要な危険因子である高血圧の環境因子を制御することが課題になると思われるが,対象者の性質と生活環境を考慮し,長期的予後の向上を見据えて,総合的なアプローチが行うことが重要である.This review article gives an outline of various aspects of life style modification in order to prevent and alleviate hypertension. The content includes salt restriction, supplementation of potassium, magnesium, calcium, polyunsaturated fatty acids and diet fiber, weight reduction, physical exercise, alcohol and coffee consumptions, cigarette smoking, and stress management. Among them, salt restriction, weight reduction and physical exercise are effective in lowering blood pressure if they are practiced continuously. In addition, such life style modification should be instructed comprehensively and the characteristics of subjects should be taken into consideration in order to prevent and improve hypertension effectively

Comparison between High-dose Telmisartan and Fixed dose Combination of Telmisartan and Hydrochlorothiazide in Patients with Hypertension

We compared treatment with a high-dose angiotensin II receptor blocker(ARB)and combination of ARB with a thiazide diuretic in 17 patients with hypertension. A randomized crossover study was performed giving 80 mg telmisartan or fixed-dose combination of 40 mg telmisartan and 12.5 mg hydrochlorothiazide for 16 weeks each. Although the clinic blood pressure was comparable between the high-dose ARB period(134/81 mmHg)and the combination period(134/82 mmHg), the morning home blood pressure was lower in the combination period than in the high-dose ARB period(138/82 vs. 151/88 mmHg, p=0.026/0.013). No significant difference was observed in urinary albumin excretion, but estimated glomerular filtration rate was lower in the combination than in the high-dose ARB period(58.9 vs. 62.1 mL/min/1.73 m^2, p=0.039). Serum uric acid was higher in the combination than in the high-dose ARB period(6.7 vs. 5.9 mg/dL p=0.022). The indices of glucose metabolism, serum lipids, oxidative stress, inflammation and adipocytokine did not significantly differ between the two periods. There was no significant difference in the measurement of endothelium-dependent vasodilation between the two periods. It is suggested that the addition of thiazide diuretic to medium-dose ARB is more effective in lengthening the hypotensive effect than high-dose ARB, however, care should be taken for the elevation of serum uric acid and the decrease in renal function

Protective Effects of Olmesartan and Azelnidipine against Cardiovascular Organ Injuries in Spontaneously Hypertensive Rats

In the treatment of hypertension, care should be taken for preventing of hypertensive organ injuries as well as lowering blood pressure to the adequate level in order to reduce the risk of cardiovascular diseases. The purpose of this study is to examine the effects of angiotensin II receptor blockers (ARB), calcium channel blockers (CCB) and their combination on the development of cardiovascular organ injuries in spontaneously hypertensive rats (SHR). Four groups of male 8-week-old SHR (n=9 each) were given vehicle(control), 10 mg/kg azelnidipine (AZL), 10 mg/kg olmesartan (OLM, n=9), or the combination of AZL and OLM(5 mg/kg each)for 12 weeks, and their effects on cardiovascular organ injuries were evaluated. Tail-cuff blood at 12 weeks was similarly lowered by AML, OLM and the combination therapy(148, 143 and 143 mmHg, respectively)as compared with the control SHR (198 mmHg). Pulse rate was significantly less in the AZL group but not in the OLM group or the combination therapy group than in the untreated control group (-27, -12, +6 bpm, respectively). The cardiac ventricular weight (AZL -12%, OLM -15%, combination -18% vs. control) and aortic thickness (AZL -17%, OLM -16%, combination -19% vs. control) were reduced by similar extents in the three groups given antihypertensive treatments. Regarding the myocardial fibrosis, left ventricular hydroxyproline content was reduced in the OLM and the combination groups but the change was not significant in the AZL group (AZL -14%,OLM -30%, combination -27% vs. control). In the echocardiographic evaluation of cardiac function, the index of left ventricular diastolic function is significantly improved in the OLM and the combination groups but not in the AZL group, while the index of systolic function was not different between the four groups. It is suggested that the antihypertensive therapy including ARB is superior to the monotherapy by CCB in preventing the myocardial fibrosis and preserving the left ventricular diastolic function