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Abstract-In this prospective, randomized, open-label, blinded end point study, we aimed to establish whether strict blood pressure control (Ͻ140 mm Hg) is superior to moderate blood pressure control (Ն140 mm Hg to Ͻ150 mm Hg) in reducing cardiovascular mortality and morbidity in elderly patients with isolated systolic hypertension. We divided 3260 patients aged 70 to 84 years with isolated systolic hypertension (sitting blood pressure 160 to 199 mm Hg) into 2 groups, according to strict or moderate blood pressure treatment. A composite of cardiovascular events was evaluated for Ն2 years. The strict control (1545 patients) and moderate control (1534 patients) groups were well matched (mean age: 76.1 years; mean blood pressure: 169.5/81.5 mm Hg). Median follow-up was 3.07 years. At 3 years, blood pressure reached 136.6/74.8 mm Hg and 142.0/76.5 mm Hg, respectively. The blood pressure difference between the 2 groups was 5.4/1.7 mm Hg. The overall rate of the primary composite end point was 10.6 per 1000 patient-years in the strict control group and 12.0 per 1000 patient-years in the moderate control group (hazard ratio: 0.89; [95% CI: 0.60 to 1.34]; Pϭ0.38). In summary, blood pressure targets of Ͻ140 mm Hg are safely achievable in relatively healthy patients Ն70 years of age with isolated systolic hypertension, although our trial was underpowered to definitively determine whether strict control was superior to less stringent blood pressure targets. Key Words: isolated systolic hypertension Ⅲ elderly Ⅲ blood pressure Ⅲ prognosis Ⅲ valsartan H igh blood pressure (BP) is well known to be a major risk factor for cardiovascular events, such as stroke and myocardial infarction, 1 and linear relationships between cardiovascular risk and both systolic and diastolic BPs, unrelated to age, have also been reported based on a meta-analysis of large cohort studies conducted worldwide. 2 In particular, systolic BP predominantly affects cardiovascular events in elderly people. 3 Numerous large clinical trials, such as the Systolic Hypertension in the Elderly Program, 4 Swedish Trial in Old Patients, 5 Medical Research Council, 6 Systolic Hypertension in Europe, 7 and Systolic Hypertension in China, 8 have provided evidence of the benefits of reducing BP in the elderly. Meta-analysis of clinical trials showed that treatment of hypertension in older adults is as beneficial as that in younger adults. 9 A recent study performed in hypertensive patients aged Ն80 years of age, the Hypertension in the Very Elderly Trial, showed that antihypertensive treatment is beneficial to reduce the risks of death from stroke, death from any cause, and heart failure. 10 These observations indicate that antihypertensive treatment is beneficial even in very elderly patients.To reduce cardiovascular risks, in general BP should be kept as low as possible based on evidence from numerous clinical trials and epidemiological data. 11 On the other hand, several epidemiological studies in the elderly, such as Vantaa and Leinden 85-Plus, reported a poor progno...

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Our study confirmed that PIGA mutations are one genetic cause of EOEE, suggesting that GPI-anchor deficiencies may be an underlying cause of EOEE.

Inflammatory responses in the kidney lead to tubulointerstitial fibrosis, a common feature of chronic kidney diseases. Here we examined the role of prostaglandin E(2) (PGE(2)) in the development of tubulointerstitial fibrosis. In the kidneys of wild-type mice, unilateral ureteral obstruction leads to progressive tubulointerstitial fibrosis with macrophage infiltration and myofibroblast proliferation. This was accompanied by an upregulation of COX-2 and PGE(2) receptor subtype EP(4) mRNAs. In the kidneys of EP(4) gene knockout mice, however, obstruction-induced histological alterations were significantly augmented. In contrast, an EP(4)-specific agonist significantly attenuated these alterations in the kidneys of wild-type mice. The mRNAs for macrophage chemokines and profibrotic growth factors were upregulated in the kidneys of wild-type mice after ureteral obstruction. This was significantly augmented in the kidneys of EP(4)-knockout mice and suppressed by the EP(4) agonist but only in the kidneys of wild-type mice. Notably, COX-2 and MCP-1 proteins, as well as EP(4) mRNA, were localized in renal tubular epithelial cells after ureteral obstruction. In cultured renal fibroblasts, another EP(4)-specific agonist significantly inhibited PDGF-induced proliferation and profibrotic connective tissue growth factor production. Hence, an endogenous PGE(2)-EP(4) system in the tubular epithelium limits the development of tubulointerstitial fibrosis by suppressing inflammatory responses.

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CCB combined with ARB, β-blocker, or thiazide diuretic was similarly effective for the prevention of cardiovascular events and the achievement of target BP.

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