Long-term caloric restriction (CR) is a robust means of reducing age-related diseases and extending life span in multiple species, but the effects in humans are unknown. The low caloric intake, long life expectancy, and the high prevalence of centenarians in Okinawa have been used as an argument to support the CR hypothesis in humans. However, no long-term, epidemiologic analysis has been conducted on traditional dietary patterns, energy balance, and potential CR phenotypes for the specific cohort of Okinawans who are purported to have had a calorically restricted diet. Nor has this cohort's subsequent mortality experience been rigorously studied. Therefore, we investigated six decades of archived population data on the elderly cohort of Okinawans (aged 65-plus) for evidence of CR. Analyses included traditional diet composition, energy intake, energy expenditure, anthropometry, plasma DHEA, mortality from age-related diseases, and current survival patterns. Findings include low caloric intake and negative energy balance at younger ages, little weight gain with age, life-long low BMI, relatively high plasma DHEA levels at older ages, low risk for mortality from age-related diseases, and survival patterns consistent with extended mean and maximum life span. This study lends epidemiologic support for phenotypic benefits of CR in humans and is consistent with the well-known literature on animals with regard to CR phenotypes and healthy aging.

Blood pressure (BP) categories defined by systolic BP (SBP) and diastolic BP (DBP) are commonly used. However, the BP category-specific risk of cardiovascular disease (CVD) has not been thoroughly investigated in different age groups. The aim of this study was to assess long-term CVD risk and its impact according to BP categories and age group. Pooling individual data from 10 cohorts, we studied 67 309 Japanese individuals (40-89 years old) who were free of CVD at baseline: we categorized them as belonging to three age groups: 'middle-aged' (40-64 years), 'elderly' (65-74 years) and 'very elderly' (75-89 years). BP was classified according to the 2009 Japanese Society of Hypertension Guidelines. Cox models were used to estimate adjusted hazard ratios for CVD deaths. We observed 1944 CVD deaths over a mean follow-up of 10.2 years. In all age groups, the overall relationship between BP category and CVD risk was positive, with a greater strength observed for younger age groups. We observed a trend of increased risk from SBP/DBP ≥ 130/85 mm Hg in the very elderly, and a significant increase from SBP/DBP ≥ 120/80 mm Hg in the other age groups. The population attributable fractions (PAFs) of CVD death in reference to the SBP/DBP<120/80 mm Hg category ranged from 23.4% in the very elderly to 60.3% in the middle-aged. We found an overall graded increase in CVD risk with higher BP category in the very elderly. The PAFs suggest that keeping BP levels low is an important strategy for primary CVD prevention, even in an elderly population.

ObjectivesTo evaluate the impact of dietary sodium and potassium (Na–K) ratio on mortality from total and subtypes of stroke, cardiovascular disease (CVD) and all causes, using 24-year follow-up data of a representative sample of the Japanese population.SettingProspective cohort study.ParticipantsIn the 1980 National Cardiovascular Survey, participants were followed for 24 years (NIPPON DATA80, National Integrated Project for Prospective Observation of Non-communicable Disease And its Trends in the Aged). Men and women aged 30–79 years without hypertensive treatment, history of stroke or acute myocardial infarction (n=8283) were divided into quintiles according to dietary Na–K ratio assessed by a 3-day weighing dietary record at baseline. Age-adjusted and multivariable-adjusted HRs were calculated using the Mantel-Haenszel method and Cox proportional hazards model.Primary outcome measuresMortality from total and subtypes of stroke, CVD and all causes.ResultsA total of 1938 deaths from all causes were observed over 176 926 person-years. Na–K ratio was significantly and non-linearly related to mortality from all stroke (p=0.002), CVD (p=0.005) and total mortality (p=0.001). For stroke subtypes, mortality from haemorrhagic stroke was positively related to Na–K ratio (p=0.024). Similar relationships were observed for men and women. The observed relationships remained significant after adjustment for other risk factors. Quadratic non-linear multivariable-adjusted HRs (95% CI) in the highest quintile versus the lowest quintile of Na–K ratio were 1.42 (1.07 to 1.90) for ischaemic stroke, 1.57 (1.05 to 2.34) for haemorrhagic stroke, 1.43 (1.17 to 1.76) for all stroke, 1.39 (1.20 to 1.61) for CVD and 1.16 (1.06 to 1.27) for all-cause mortality.ConclusionsDietary Na–K ratio assessed by a 3-day weighing dietary record was a significant risk factor for mortality from haemorrhagic stroke, all stroke, CVD and all causes among a Japanese population.

High-dose thyroid hormone replacement has been recommended for treatment of myxedema coma (MC) while questions of safety of the therapy and of efficacy of low-dose thyroid hormone replacement have not been systematically addressed. We treated 8 patients with MC in a period of 18 years, the first 3 with high-dose intravenous injections of levotriiodothyronine (LT3) and the other 5 patients with a smaller amount of either LT3 or levothyroxine (LT4). Two of the first 3 patients died of pneumonia and the other 5 recovered despite pulmonary abnormalities at the outset. To find factors associated with fatal outcome after treatment, the MEDLINE database was searched for MC cases with data of thyroid hormone replacement and outcome within 1 month of therapy. Clinical data for our 5 patients and 82 cases from the MEDLINE search were pooled and factors associated with mortality were sought among age, gender, presence of cardiac or pulmonary complications, and doses of thyroid hormone by multiple logistic regression analysis. It revealed that greater age, cardiac complications, and high-dose thyroid hormone replacement (LT4 > or = 500 microg/d or LT3 > or = 75 microg/d) were significantly associated with a fatal outcome within 1 month of treatment. Elderly MC patients can be treated with low-dose hormone replacement. A bolus of 500 microg LT4, especially by mouth or via nasogastric tube, appears to be tolerated by younger patients (< 55 years) without cardiac complication. The conclusion remains to be confirmed in more patients.

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