Visceral obesity is not an independent risk factor of mortality in subjects over 65 years.

The aim of the study was to determine the role of obesity evaluated by body mass index (BMI), waist circumference (WC), and their combined effect on all-cause mortality according to age and related risk factors. This study included 119,090 subjects (79,325 men and 39,765 women), aged from 17 years to 85 years, who had a general health checkup at the Centre d'Investigations Préventives et Cliniques, Paris, France. The mean follow-up was 5.6±2.4 years. The prevalence of obesity, defined by WC and BMI categories, was determined according to age groups (<55, 55-65, >65 years). All-cause mortality according to obesity and age was determined using Cox regression analysis, adjusted for related risk factors and previous cardiovascular events. For the entire population, WC adjusted for BMI, an index of central obesity, was strongly associated with mortality, even after adjustment for hypertension, dyslipidemia, and diabetes. The prevalence of obesity increased with age, notably when defined by WC. Nonetheless, the association between WC adjusted for BMI and mortality was not observed in subjects>65 years old (hazard ratio [HR]=1.010, P=NS) but was found in subjects<55 (HR=1.030, P<0.0001) and 55-65 years old (HR=1.023, P<0.05). By contrast, hypertension (HR=1.31, P<0.05), previous cardiovascular events (HR=1.98, P<0.05), and smoking (HR=1.33, P<0.05) remained associated with mortality even after age 65. In conclusion, WC adjusted for BMI is strongly and independently associated with all-cause mortality before 65 years of age, after taking into account the associated risk factors. This relationship disappears in subjects>65 years of age, suggesting a differential impact of visceral fat deposition according to age.

The association between the body mass index and 4-year all-cause mortality in older hospitalized patients.

BACKGROUND: Association between body mass index (BMI) and long-term mortality is poorly studied in older hospitalized populations. METHODS: The researchers prospectively studied the impact of the BMI, comorbidities, and malnutrition on long-term mortality in 444 patients (mean age 85.3±6.7 years; 74.0% women) receiving geriatric inpatient care. All-cause mortality was determined using simple and multiple Cox proportional hazard models. RESULTS: Higher BMI was associated with a higher prevalence of diabetes, hypertension, and heart failure, but with a lower prevalence of malignancies. Four-year all-cause mortality was inversely associated with a BMI greater than or equal to 30kg/m(2) (hazard ratio = 0.59, p = .037) and positively associated with age, male gender, several individual comorbidities, and the global disease load determined by the Cumulative Illness Rating scale. The inverse association between a BMI greater than or equal to 30 and mortality remained significant after adjustment for age, gender, smoking, individual comorbidities (including heart failure and malignancies), Cumulative Illness Rating scale scores, and malnutrition parameters (hazard ratio = 0.52, p = .015). One-year mortality was associated with the Cumulative Illness Rating scale score but not with BMI categories. There were no survival differences between patients in low (<20.0) and intermediate (20.0-24.9 and 25.0-29.9) BMI categories. CONCLUSIONS: A BMI greater than or equal to 30 is associated with better long-term survival in hospitalized older patients, even after extensive adjustment for comorbidities, malnutrition, and smoking. Conversely, a low BMI (<20-25) is not associated with excess mortality, likely due to the overriding impact of multiple comorbidities. The researchers' observations have important implications for the mortality risk stratification in older high-risk patients.

The prognostic significance of malnutrition as assessed by the Mini Nutritional Assessment (MNA) in older hospitalized patients with a heavy disease burden.

BACKGROUND & AIMS: Malnutrition is common in older persons. However, it is unclear whether malnutrition diagnosed with the Mini Nutritional Assessment (MNA) predicts mortality in older hospitalized patients. METHODS: We prospectively studied the impact of the MNA-short form (MNA-SF) and co-morbidities on long-term mortality in 444 patients (mean age 85.3 ± 6.7; 74.0% women) receiving geriatric inpatient care. In a cross-sectional study we studied the interplay between the MNA, nutritional markers and co-morbidities (using the Cumulative Illness Rating Scale, CIRS). RESULTS: The prevalence of malnutrition and "at risk of malnutrition", defined by MNA-SF, was 25.5 and 50.5% respectively in our prospective study. CIRS scores (HR = 1.09, p < 0.001) and a low BMI (HR = 0.96, p < 0.05), but not the MNA-SF (HR = 0.79 and 0.89 for "at risk" and malnutrition respectively, P = NS), were associated with 4-year mortality. CIRS scores, albumin and other nutritional markers were similar between MNA categories. High CIRS scores and hypoalbuminemia were observed even in patients with normal MNA scores. There was good agreement (>80%) between the MNA-SF and the complete MNA. CONCLUSIONS: Malnutrition as diagnosed with the MNA at admission failed to predict long-term mortality in older inpatients, likely due to the overriding impact of co-morbidities and acute disease.

Effect of age on interdependence and hierarchy of cardiovascular risk factors in hypertensive patients.

The prognostic significance, interdependence, and hierarchy of cardiovascular risk factors could evolve with advancing age. Our study reports on the interdependence among blood pressure (BP), other metabolic syndrome components, and high-sensitivity C-reactive protein according to age in hypertensive subjects. A total of 5,712 nondiabetic patients (50.1% men, age range 40 to 95 years) evaluated in outpatient hypertension clinics were included and divided into 5 age groups (age 40 to 49, 50 to 59, 60 to 69, 70 to 79, and >80 years). BP, evaluated by both office and 24-hour ambulatory BP monitoring, and the metabolic and inflammation parameters were determined after a ≥2-week drug washout period. The prevalence of the metabolic syndrome (Adult Treatment Panel III definition) remained stable across the age groups. We observed a stable or increased association between waist circumference and insulin resistance (Homeostasis Model of Assessment-Insulin Resistance index) and fasting plasma glucose. However, the association between waist circumference and ambulatory BP monitoring systolic BP (r(2) decrease from 9.9% to 1.0%, p <0.001), high-density lipoprotein cholesterol (r(2) decreased from 21% to 4.9%, p = 0.002), and triglyceride levels (r(2) decreased from 17.5% to 1.9%, p <0.001) decreased with age. High-sensitivity C-reactive protein correlated with all metabolic syndrome components in all age groups (p <0.001 for all). It became the strongest determinant of ambulatory BP monitoring systolic BP (p <0.001) and high-density lipoprotein cholesterol (p <0.05) in patients >80 years old. In contrast, its association with waist circumference markedly decreased. In conclusion, hypertension and dyslipidemia, but not fasting plasma glucose, dissociate from central obesity with advancing age. They are increasingly determined by low-grade inflammation, independently of central obesity. These changing associations might underlie the weakening of obesity as a cardiovascular risk factor in older persons.

Attitudes and approaches to decision making about antihypertensive treatment in elderly patients.

OBJECTIVE: Optimal antihypertensive therapy in very old subjects requires their understanding and acceptance. We investigated elderly patients' willingness to accept antihypertensive therapy and their desire for information and for participation in medical decisions. METHODS: After standardized explanations about hypertension and its treatment, 120 patients (mean age 83.8 ± 7.4 years) were asked whether they would accept hypertension treatment in 15 hypothetical scenarios with different outcomes (myocardial infarction/heart failure, stroke, and death), absolute risks/risk reductions, and risk of side effects. RESULTS: Fifty percent to 60% of patients accepted treatment in all scenarios; only 4% to 7% clearly refused it, and 30% to 40% were unsure. Paradoxically, the Autonomy Preference Index (API) indicated a variable, overall low desire for participation in medical decisions (mean score 58.9 ± 13.9 mean ± SD, on 100), including about hypertension, but patients wanted to receive extensive medical information (mean score 69.6 ± 17.2). CONCLUSIONS: Our data indicate that many patients prefer to delegate the final decision to their physician, although most want to receive extensive information. Although the decision to treat belongs to the physician, initial acceptance of antihypertensive therapy does not imply that patients really understand and adhere to it. True understanding and acceptance of treatment requires attention to patients' preferences and repeated explanations during follow-up.

The impact of the metabolic syndrome--but not of hypertension--on all-cause mortality disappears in the elderly.

OBJECTIVE: The metabolic syndrome predicts the risk of cardiovascular and all-cause death, but its clinical relevance in the elderly remains debatable. We aimed to determine the impact of the metabolic syndrome on all-cause mortality according to age, in comparison with hypertension alone. METHODS: We studied 129 655 participants (82 110 men and 47 545 women) undergoing a standard health check-up at the Investigations Préventives et Cliniques center (Paris, France). Mean follow-up was 4.9±2.6 years. The prevalence of the metabolic syndrome and its components was determined according to age group (<55, 55-65, >65 years old). All-cause mortality according to metabolic syndrome and age was determined using Cox regression model analysis, unadjusted or adjusted for age, sex, smoking and other confounding factors. RESULTS: The prevalence of the metabolic syndrome and all its components except lipid parameters strongly increased with age. All-cause mortality associated with the metabolic syndrome (using three different definitions) was significantly elevated in participants below 55 years old, and was little affected by adjustment for confounding factors. However, it decreased from 1.77 (1.45-2.16) in participants below 55 years old to 1.12 (0.84-1.48) in participants above 65 years old [hazard ratio (95% confidence interval); National Cholesterol Education Program definition]. Waist circumference, fasting blood glucose and lipid parameters failed to predict mortality in participants above 65 years old. In contrast, hypertension (blood pressure>140/90 mmHg or treatment) remained a significant predictor of all-cause mortality [hazard ratio 1.30 (95% confidence interval 1.02-1.66)] in participants above 65 years old. CONCLUSIONS: In a setting representative of primary care, hypertension but not the metabolic syndrome remains a strong risk factor for all-cause mortality in participants above 65 years old.

[Anemia in the elderly: a frequent condition that should not be overlooked]. / L'anémie du sujet âgé: une pathologie fréquente à ne pas banaliser.

Anemia is a frequent disease in elderly persons, but is often undertreated and misunderstood as a physiologic consequence of aging. Nevertheless, its association with some negative clinical impacts is well known and widely documented in the literature.

Evidence against a direct role of klotho in insulin resistance.

The klotho gene may be involved in the aging process. Klotho is a coactivator of FGF23, a regulator of phosphate and vitamin D metabolism. It has also been reported to be downregulated in insulin resistance syndromes and paradoxically to directly inhibit IGF-1 and insulin signaling. Our aim was to study klotho's regulation and effects on insulin and IGF-1 signaling to unravel this paradox. We studied klotho tissue distribution and expression by quantitative real-time polymerase chain reaction and Western blotting in obese Zucker rats and high-fat fed Wistar rats, two models of insulin resistance. Klotho was expressed in kidneys but at much lower levels (<1.5%) in liver, muscle, brain, and adipose tissue. There were no significant differences between insulin resistant and control animals. We next produced human recombinant soluble klotho protein (KLEC) and studied its effects on insulin and IGF-1 signaling in cultured cells. In HEK293 cells, FGF23 signaling (judged by FRS2-alpha and ERK1/2 phosphorylation) was activated by conditioned media from KLEC-producing cells (CM-KLEC); however, IGF-1 signaling was unaffected. CM-KLEC did not inhibit IGF-1 and insulin signaling in L6 and Hep G2 cells, as judged by Akt and ERK1/2 phosphorylation. We conclude that decreased klotho expression is not a general feature of rodent models of insulin resistance. Further, the soluble klotho protein does not inhibit IGF-1 and/or insulin signaling in HEK293, L6, and HepG2 cells, arguing against a direct role of klotho in insulin signaling. However, the hypothesis that klotho indirectly regulates insulin sensitivity via FGF23 activation remains to be investigated.

Tuberculous Cutaneous Ulcers Associated with Miliary Tuberculosis in an Elderly Woman.

Skin localizations in disseminated tuberculosis may present a clinical resistant evolution. An 81-year-old woman, treated by long-term steroids and methotrexate for rheumatoid polyarthritis, developed a disseminated tuberculosis in chest, bones and skin. While pulmonary symptoms quickly improved under conventional tuberculostatic drugs, skin ulcers showed positive cultures for 5 months and healed after 12 months of treatment.

Tissue-type plasminogen activator (t-PA) is stored in Weibel-Palade bodies in human endothelial cells both in vitro and in vivo.

Vascular endothelial cells are thought to be the main source of plasma tissue-type plasminogen activator (t-PA) and von Willebrand factor (VWF). Previous studies have suggested that both t-PA and VWF are acutely released in response to the same stimuli, both in cultured endothelial cells and in vivo. However, the subcellular storage compartment in endothelial cells has not been definitively established. We tested the hypothesis that t-PA is localized in Weibel-Palade (WP) bodies, the specialized endothelial storage granules for VWF. In cultured human umbilical vein endothelial cells (HUVECs), t-PA was expressed in a minority of cells and found in WP bodies by immunofluorescence. After up-regulation of t-PA synthesis either by vascular endothelial growth factor (VEGF) and retinoic acid or by sodium butyrate, there was a large increase in t-PA-positive cells. t-PA was exclusively located to WP bodies, an observation confirmed by immunoelectron microscopy. Incubation with histamine, forskolin, and epinephrine induced the rapid, coordinate release of both t-PA and VWF, consistent with a single storage compartment. In native human skeletal muscle, t-PA was expressed in endothelial cells from arterioles and venules, along with VWF. The 2 proteins were found to be colocalized in WP bodies by immunoelectron microscopy. These data indicate that t-PA and VWF are colocalized in WP bodies, both in HUVECs and in vivo. Release of both t-PA and VWF from the same storage pool likely accounts for the coordinate increase in the plasma level of the 2 proteins in response to numerous stimuli, such as physical activity, beta-adrenergic agents, and 1-deamino-8d-arginine vasopressin (DDAVP) among others.