Experimental studies incriminate glomerular hypertension in mediating progressive renal damage after any of a variety of initiating injuries. Prevention of glomerular hypertension by dietary protein restriction or antihypertensive therapy lessens progressive glomerular damage in several experimental models of chronic renal disease. Glomerular hypertension and hyperfiltration also occur in humans with diabetes mellitus, solitary or remnant kidneys, and various forms of acquired renal disease. Clinical studies indicate that dietary protein restriction and antihypertensive therapy also slow progression in many of these disorders. Large multicenter trials confirm the beneficial effects of these therapeutic maneuvers on the rate of progression of chronic renal disease.

These results suggest there may be multiple routes to achieving exceptional longevity and that there are sex differences according to which route is taken. These routes represent different phenotypes and thus likely different genotypes of centenarians. The identification of three types of centenarians, Survivors, Delayers, and Escapers, provides direction for future study into the factors that determine exceptional longevity.

Objective To investigate whether angiotensin receptor blockers protect against Alzheimer's disease and dementia or reduce the progression of both diseases. Design Prospective cohort analysis. Setting Administrative database of the US Veteran Affairs, 2002-6. Population 819 491 predominantly male participants (98%) aged 65 or more with cardiovascular disease. Main outcome measures Time to incident Alzheimer's disease or dementia in three cohorts (angiotensin receptor blockers, lisinopril, and other cardiovascular drugs, the "cardiovascular comparator") over a four year period (fiscal years 2003-6) using Cox proportional hazard models with adjustments for age, diabetes, stroke, and cardiovascular disease. Disease progression was the time to admission to a nursing home or death among participants with pre-existing Alzheimer's disease or dementia. Results Hazard rates for incident dementia in the angiotensin receptor blocker group were 0.76 (95% confidence interval 0.69 to 0.84) compared with the cardiovascular comparator and 0.81 (0.73 to 0.90) compared with the lisinopril group. Compared with the cardiovascular comparator, angiotensin receptor blockers in patients with pre-existing Alzheimer's disease were associated with a significantly lower risk of admission to a nursing home (0.51, 0.36 to 0.72) and death (0.83, 0.71 to 0.97). Angiotensin receptor blockers exhibited a dose-response as well as additive effects in combination with angiotensin converting enzyme inhibitors. This combination compared with angiotensin converting enzyme inhibitors alone was associated with a reduced risk of incident dementia (0.54, 0.51 to 0.57) and admission to a nursing home (0.33, 0.22 to 0.49). Minor differences were shown in mean systolic and diastolic blood pressures between the groups. Similar results were observed for Alzheimer's disease. Conclusions Angiotensin receptor blockers are associated with a significant reduction in the incidence and progression of Alzheimer's disease and dementia compared with angiotensin converting enzyme inhibitors or other cardiovascular drugs in a predominantly male population. INTRODUCTIONDementia, including Alzheimer's disease, is one of the major threats to public health as people age. Dementia is also an important economic cost to society because affected people may spend extended periods in nursing homes. The causes of dementia, and Alzheimer's disease in particular, are complex, but evidence increasingly points to three main risk factors-age, the accumulation of amyloid β in the brain, and the deterioration of the cardiovascular system. Cardiovascular dysfunction is also strongly related to other forms of dementia. Studies have found that cardiovascular risk factors in mid-life, such as hypercholesterolaemia, hypertension, and diabetes contribute to the development of dementia.1-5 Drugs used to treat these risk factors may also reduce the incidence of dementia.

For patients with the acute coronary syndrome who are at low or intermediate risk for bleeding, the cardiovascular benefits of warfarin outweigh the bleeding risks.