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BACKGROUND: A high body mass index (BMI) confers a paradoxical survival benefit in patients with heart failure (HF) or diabetes mellitus (DM). There is, however, controversy whether an obesity paradox is also present in patients with HF and concomitant DM. In addition, the influence of glycaemic control and diabetes treatment on the presence or absence of the obesity paradox in patients with HF and DM is unknown. METHODS: We identified 2936 patients with HF with reduced ejection fraction (HFrEF) in the HF registries of the universities of Heidelberg, Germany, and Hull, UK (general sample). Of these, 598 (20%) were treated for concomitant DM (DM subgroup). The relationship between BMI and all-cause mortality was analysed in both the general sample and the DM subgroup. Patients with concomitant DM were stratified according to HbA1c levels or type of diabetes treatment and analyses were repeated. RESULTS: We found an inverse BMI-mortality relationship in both the general sample and the DM subgroup. However, the obesity paradox was less pronounced in patients with diabetes treated with insulin and it disappeared in those with poor glycaemic control as defined by HbA1c levels > 7.5%. CONCLUSION: In patients with HFrEF, a higher BMI is associated with better survival irrespective of concomitant DM. However, insulin treatment and poor glycaemic control make the relationship much weaker.

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Introducción: En la vejez, el valor predictivo de los factores de riesgo tradicionales es inconsistente. Con el aumento de la edad, las asociaciones entre los factores de riesgo tradicionales y las enfermedades cardiovasculares cambian. Objetivo: Recopilar información sobre los factores de riesgo tradicionales de enfermedad cardiovascular y su valor predictivo en el adulto mayor. Métodos: En el policlínico Ramón López Peña de Santiago de Cuba, en el período comprendido entre enero y mayo de 2022, se realizó una revisión sobre el tema. La búsqueda se realizó a partir de las bases de datos Pubmed, Infomed y SciELO, sin restricción de fechas, en los idiomas español e inglés. Resultados: Los hallazgos más recientes sugieren que los factores de riesgo tradicionales para la enfermedad cardiovascular podrían ser predictores más débiles del riesgo futuro en los ancianos, mientras que la fuerza de otros factores aumenta con la edad. Las personas mayores constituyen un subgrupo especial en el que otros factores como la polifarmacia, la hipotensión ortostática, la depresión y la condición física han demostrado ser determinantes potencialmente importantes de su riesgo cardiovascular. Conclusiones: El valor predictivo de la presión arterial, el colesterol y la obesidad en los ancianos disminuye o incluso se invierte, mientras que otros como la polifarmacia, la fragilidad y el deterioro cognitivo parecen ser prometedores(AU)

Introduction: In old age, the predictive value of common risk factors is inconsistent. With increasing age, the associations between common risk factors and cardiovascular disease change. Objective: To collect information on the common risk factors for cardiovascular disease and their predictive value in the elderly. Methods: A review on this subject was carried out at Ramón López Peña community clinic in Santiago de Cuba, from January to May 2022. The search was carried out from Pubmed, Infomed and SciELO databases, with no date restrictions, in Spanish and English. Results: The most recent findings suggest that common risk factors for cardiovascular disease might be weaker predictors of future risk in the elderly, while the strength of other factors increases with age. Older people constitute a special subgroup in which other factors such as polypharmacy, orthostatic hypotension, depression, and physical condition have been shown to be potentially important determinants of their cardiovascular risk. Conclusions: The predictive value of blood pressure, cholesterol and obesity in the elderly decreases or even reverses, while others such as polypharmacy, frailty and cognitive impairment appear to be promising(AU)

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BACKGROUND: The existence of a paradoxical association between overweight/obesity and survival benefits, the so-called obesity paradox, in heart failure (HF) as well as coronary artery disease (CAD) remains contentious. Previously, we reported that a past history of CAD negated the obesity paradox in the general population with acute HF. Herein, we further focused on HF complicating acute myocardial infarction (AMI) and compared the prognostic effects of overweight/obesity with respect to the severity of HF. METHODS: We conducted a multicenter retrospective study of 7265 consecutive patients with AMI. The severity of HF was categorized according to the Killip classification. Overweight/obesity was defined as a body mass index (BMI) of ≥25 kg/m2. The interaction between overweight/obesity and the Killip classification for in-hospital mortality was tested in the entire cohort. Multivariable logistic regression analyses were performed to examine the effects of overweight/obesity on in-hospital mortality. RESULTS: Across the entire study cohort, 1931 patients had HF. Overweight/obesity had a significant association with reductions in in-hospital mortality in patients with mild HF (Killip class II; odds ratio [OR], 0.284; P = 0.019). Conversely, overweight/obesity was a significant risk factor for in-hospital mortality in patients with severe HF (Killip class IV; OR, 2.152; P = 0.001). The effects of overweight/obesity on in-hospital mortality in patients with moderate HF (Killip class III) were intermediate between those with mild HF and severe HF. CONCLUSION: Opposing effects of overweight/obesity on in-hospital mortality in patients with mild HF versus severe HF were demonstrated, suggesting a balance between beneficial and deleterious effects of overweight/obesity may be inclined toward the latter with the severity of HF complicating AMI.

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Background: In the general population with coronavirus disease 2019 (COVID-19), obesity is associated with an increased risk of mortality. Given the typically observed obesity paradox among patients on kidney function replacement therapy (KFRT), especially dialysis patients, we examined the association of obesity with mortality among dialysis patients or living with a kidney transplant with COVID-19. Methods: Data from the European Renal Association COVID-19 Database (ERACODA) were used. KFRT patients diagnosed with COVID-19 between 1 February 2020 and 31 January 2021 were included. The association of Quetelet's body mass index (BMI) (kg/m2), divided into: <18.5 (lean), 18.5-24.9 (normal weight), 25-29.9 (overweight), 30-34.9 (obese I) and ≥35 (obese II/III), with 3-month mortality was investigated using Cox proportional-hazards regression analyses. Results: In 3160 patients on KFRT (mean age: 65 years, male: 61%), 99 patients were lean, 1151 normal weight (reference), 1160 overweight, 525 obese I and 225 obese II/III. During follow-up of 3 months, 28, 20, 21, 23 and 27% of patients died in these categories, respectively. In the fully adjusted model, the hazard ratios (HRs) for 3-month mortality were 1.65 [95% confidence interval (CI): 1.10, 2.47], 1 (ref.), 1.07 (95% CI: 0.89, 1.28), 1.17 (95% CI: 0.93, 1.46) and 1.71 (95% CI: 1.27, 2.30), respectively. Results were similar among dialysis patients (N = 2343) and among those living with a kidney transplant (N = 817) (Pinteraction = 0.99), but differed by sex (Pinteraction = 0.019). In males, the HRs for the association of aforementioned BMI categories with 3-month mortality were 2.07 (95% CI: 1.22, 3.52), 1 (ref.), 0.97 (95% CI: 0.78. 1.21), 0.99 (95% CI: 0.74, 1.33) and 1.22 (95% CI: 0.78, 1.91), respectively, and in females corresponding HRs were 1.34 (95% CI: 0.70, 2.57), 1 (ref.), 1.31 (95% CI: 0.94, 1.85), 1.54 (95% CI: 1.05, 2.26) and 2.49 (95% CI: 1.62, 3.84), respectively. Conclusion: In KFRT patients with COVID-19, on dialysis or a kidney transplant, obesity is associated with an increased risk of mortality at 3 months. This is in contrast to the obesity paradox generally observed in dialysis patients. Additional studies are required to corroborate the sex difference in the association of obesity with mortality.

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BACKGROUND AND AIMS: Reduced sleep quality is common in advanced age. Poor sleep quality is associated with adverse outcomes, chiefly cardiovascular, in young and middle-aged subjects, possibly because of its association with metabolic syndrome (MetS). However, the correlates of sleep quality in oldest populations are unknown. We evaluated the association of sleep quality with MetS in a cohort of subjects aged 90+. METHODS AND RESULTS: We analysed data of 343 subjects aged 90+ living in the Mugello area (Tuscany, Italy). Quality of sleep was assessed using the Pittsburgh Sleep Quality Assessment Index (PSQI). Good quality of sleep was defined by a PSQI score < 5. MetS was diagnosed according to the National Cholesterol Education Program's ATP-III criteria; 83 (24%) participants reported good quality of sleep. MetS was diagnosed in 110 (24%) participants. In linear and logistic models, MetS was inversely associated with PSQI score ((B = - 1.04; 95% CI - 2.06 to - .03; P = .044), with increased probability of good sleep quality (OR = 2.52; 95% CI 1.26-5.02; P = .009), and with a PSQI below the median (OR = 2.11; 95% CI 1.11-3.40, P = .022), after adjusting. None of the single components of MetS were associated with PSQI (all P values > .050). However, an increasing number of MetS components was associated with increasing probability of good quality of sleep (P for trend = .002), and of PSQI below the median (P for trend = .007). Generalized Additive Model analysis documented no smoothing function suggestive of nonlinear association between PSQI and MetS. CONCLUSION: Our results confirm a high prevalence of poor sleep quality in oldest age; however, in these subjects, MetS seems to be associated with better sleep quality. Additional larger, dedicated studies are required to confirm our results, and, if so, to identify the subsystems involved and the potential therapeutic implications of such an association.

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PURPOSE: To investigate the association of preexisting hypertension at admission with the mortality in patients with systolic heart failure (HF). METHOD: We prospectively investigated the association of preexisting hypertension with the mortality among 1351 patients with HF in Taiwan during an average 12 months (range: 8 months-18 months) follow-up period. A multivariate cox regression analysis for the overall cohort and a subgroup analysis by age were performed. RESULTS: After adjustment for all potential risk factors, the associations of preexisting hypertension with cardiovascular mortality were significantly reduced in the overall cohort and those aged less than 65 years (hazard ratios (HR): 0.53, 95% confidence intervals (CI): 0.33-0.84, and 0.28, 95% CI: 0.11-0.67, respectively). However, the associations with all-cause mortality were not significantly different in these two groups (HR: 0.77, 95% CI: 0.54-1.09, and 0.59, 95% CI: 0.32-1.07, respectively). Furthermore, the associations were all nonsignificant in the patients aged older than 65 years. CONCLUSION: Preexisting hypertension have an inverse association with cardiovascular mortality in the Asian patients with systolic HF, particularly for those with younger ages.

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Leishmania biomarker discovery remains an important challenge that needs to be revisited in light of our increasing knowledge on parasite-specific biology, notably its genome instability. In the absence of classical transcriptional regulation in these early-branching eukaryotes, fluctuations in transcript abundance can be generated by gene and chromosome amplifications, which have been linked to parasite phenotypic variability with respect to virulence, tissue tropism, and drug resistance. Conducting in vitro evolutionary experiments to study mechanisms of Leishmania environmental adaptation, we recently validated the link between parasite genetic amplification and fitness gain, thus defining gene and chromosome copy number variations (CNVs) as important Leishmania biomarkers. These experiments also demonstrated that long-term Leishmania culture adaptation can strongly interfere with epidemiologically relevant, genetic signals, which challenges current protocols for biomarker discovery, all of which rely on in vitro expansion of clinical isolates. Here we propose an experimental framework independent of long-term culture termed "reverse" epidemiology, which applies established protocols for functional genetic screening of cosmid-transfected parasites in animal models for the identification of clinically relevant genetic loci that then inform targeted field studies for their validation as Leishmania biomarkers.

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Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure are also found to relate to outcomes in the geriatric population, but in a differing direction. A higher body mass index, hypercholesterolemia and hypertension are not harmful but even permit better survival at advancing age. This phenomenon is called "reverse epidemiology" or "risk factor paradox" and is also detected in a variety of chronic disease states such as chronic heart failure. Accordingly, a low BMI, blood pressure and cholesterol values are associated with a worse prognosis. Several possible causes are hypothesized to explain this elderly paradox, but this phenomenon remains controversial and its underlying reasons are poorly understood. The aim of this review is to recognize the factors behind this intriguing phenomenon and analyse the consequences that it can bring in the management of the cardiovascular therapy in elderly patient. Finally, a new phenotype identified as "catabolic syndrome" has been postulated.

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BACKGROUND: Stroke is the third leading cause of cardiovascular mortality in dialysis patients. The objective of this study was to assess the extent of stroke in chronic hemodialysis patients. METHODS: Historical cohort of patients enrolled in two hemodialysis (HD) centers from January 1, 2010 to December 31, 2011, including 191 patients (mean age 52 years, 68% men). Incidence curves and survival time analysis between the first day of HD and the end of the study were described by the Kaplan-Meier method. Independent stroke predictors were identified by multiple logistic regression analysis. P < 0.05 defined the level of statistical significance. RESULTS: 12 incident stroke were recorded during the study period, with 1622.1 person-months (PM), a stroke incidence rate of 7.4 cases per 1000 PM (95% CI = 7.35-7.44) at the point date. The incidence of stroke at 6 months, 12 months and 24 months was 9.8%, 11.9% and 13%, respectively. Only the absence of arterial hypertension (RR = 5.7, 95% CI: 1.52-21.42) emerged as an independent determinant of stroke. CONCLUSION: The high incidence of stroke in Kinshasa HD centers is partially explained by reverse epidemiology. Efforts must be made to understand this phenomenon in order to reduce its impact.

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Obesity, a risk factor for de novo chronic kidney disease (CKD), confers survival advantages in advanced CKD. This so-called obesity paradox is the archetype of the reverse epidemiology of cardiovascular risks, in addition to the lipid, blood pressure, adiponectin, homocysteine, and uric acid paradoxes. These paradoxical phenomena are in sharp contradistinction to the known epidemiology of cardiovascular risks in the general population. In addition to advanced CKD, the obesity paradox has also been observed in heart failure, chronic obstructive lung disease, liver cirrhosis, and metastatic cancer, as well as in the elderly. These are populations in whom protein-energy wasting and inflammation are strong predictors of early death. Both larger muscle mass and higher body fat provide longevity in these patients, whereas thinner body habitus and weight loss are associated with higher mortality. Muscle mass appears to be superior to body fat in conferring an even greater survival. The obesity paradox may be the result of a time discrepancy between competing risk factors, i.e., overnutrition as the long-term killer versus undernutrition as the short-term killer. Hemodynamic stability of obesity, lipoprotein defense against circulating endotoxins, protective cytokine profiles, toxin sequestration of fat mass, and antioxidation of muscle may play important roles. Despite claims that obesity paradox is a statistical fallacy and a result of residual confounding, the consistency of data and other causality clues suggest a high biologic plausibility. Examining the causes and consequences of the obesity paradox may help discover important pathophysiologic mechanisms leading to improved outcomes in patients with CKD.

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BACKGROUND: Mortality is extremely high immediately after the transition to dialysis therapy, but the association of blood pressure (BP) before dialysis therapy initiation with mortality after dialysis therapy initiation remains unknown. STUDY DESIGN: Observational study. SETTING & PARTICIPANTS: 17,729 US veterans transitioning to dialysis therapy in October 2007 to September 2011, with a median follow-up of 2.0 years. PREDICTOR: Systolic (SBP) and diastolic BP (DBP) averaged over the last 1-year predialysis transition period as 6 (<120 to ≥160mmHg in 10-mmHg increments) and 5 (<60 to ≥90mmHg in 10-mmHg increments) categories, respectively, and as continuous measures. OUTCOMES & MEASUREMENTS: Postdialysis all-cause mortality, assessed over different follow-up periods (ie, <3, 3-<6, 6-<12, and ≥12 months after dialysis therapy initiation) using Cox regressions adjusted for demographics, comorbid conditions, medications, cardiovascular medication adherence, body mass index, estimated glomerular filtration rate, and type of vascular access. RESULTS: Mean predialysis SBP and DBP were 141.2±16.1 (SD) and 73.7±10.6mmHg, respectively. There was a reverse J-shaped association of SBP with all-cause mortality, with significantly higher mortality seen with SBP<140mmHg. Mortality risks associated with lower SBP were greatest in the first 3 months after dialysis therapy initiation, with multivariable-adjusted HRs of 2.40 (95% CI, 1.96-2.93), 1.99 (95% CI, 1.66-2.40), 1.35 (95% CI, 1.13-1.62), 0.98 (95% CI, 0.78-1.22), and 0.76 (95% CI, 0.57-1.00) for SBP <120, 120 to <130, 130 to <140, 150 to <160, and ≥160 (vs 140-<150) mmHg, respectively. No consistent association was observed between predialysis DBP and postdialysis mortality. LIMITATIONS: Results cannot be inferred to show causality and may not be generalizable to women or the general US population. CONCLUSIONS: Lower predialysis SBP is associated with higher all-cause mortality in the immediate postdialysis period. Predialysis DBP showed no consistent association with postdialysis mortality. Further studies are needed to clarify ideal predialysis SBP levels among incident dialysis patients as a potential means to improve the excessively high early dialysis mortality.

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BACKGROUND: In patients with chronic heart failure (CHF) increasing levels of total serum cholesterol are associated with improved survival - while statin usage is not. The impact of statin treatment on the "reverse epidemiology" of cholesterol is unclear. METHODS: 2992 consecutive patients with non-ischemic CHF due to left ventricular systolic dysfunction from the Norwegian CHF Registry and the CHF Registries of the Universities of Hull, UK, and Heidelberg, Germany, were studied. 1736 patients were individually double-matched on both cholesterol levels and the individual propensity scores for statin treatment. All-cause mortality was analyzed as a function of baseline cholesterol and statin use in both the general and the matched sample. RESULTS: 1209 patients (40.4%) received a statin. During a follow-up of 13,740 patient-years, 360 statin users (29.8%) and 573 (32.1%) statin non-users died. When grouped according to total cholesterol levels as low (≤3.6mmol/L), moderate (3.7-4.9mmol/L), high (4.8-6.2mmol/L), and very high (>6.2mmol/L), we found improved survival with very high as compared with low cholesterol levels. This association was present in statin users and non-users in both the general and matched sample (p<0.05 for each group comparison). The negative association of total cholesterol and mortality persisted when cholesterol was treated as a continuous variable (HR 0.83, 95%CI 0.77-0.90, p<0.001 for matched patients), but it was less pronounced in statin users than in non-users (F-test p<0.001). CONCLUSIONS: Statins attenuate but do not eliminate the reverse epidemiological association between increasing total serum cholesterol and improved survival in patients with non-ischemic CHF.

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BACKGROUND AND OBJECTIVE: An inverse relationship has been described between blood pressure and the prognosis in heart failure (HF). The characteristics of this relationship are not well unknown. The objective of this study was to determine if this relationship is maintained in a non-selected cohort of patients with HF and if it can be modified by treatment. MATERIAL AND METHODS: Prospective study of cohorts including patients hospitalized for decompensated HF in Internal Medicine departments and followed as outpatients in a monographic consultation. Patients were classified according to their levels of systolic (SBP) and diastolic blood pressure (DBP). Clinical characteristics, all-cause mortality and readmissions after the first, third and sixth month of follow-up were analysed. RESULTS: Two hundred and twenty-one patients were included after their admission to the hospital for acute HF. Mean patient age was 79.5 years(SD 8.09); 115 patients were male. No significant differences between SBP quartiles and basal characteristics were found. Patients with lower SBP (Q1) had higher mortality rates (20%, P<.05). No significant differences between mortality/readmissions and DBP were found. However, the Kaplan-Meier analysis showed higher all-cause mortality rates for the group of patients with lower SBP and DBP (log-rank=0.011 and 0.041, respectively). The pharmacological treatment did not differ significantly between both study groups. CONCLUSION: For non-selected patients suffering HF, higher SBP upon the admission is associated with significantly lower all-cause mortality rates during follow-up. Pharmacological treatment of HF does not seem to influence this inverse relationship between SBP at admission and patient mortality.

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BACKGROUND & AIMS: Falls are a major threat for patients with Parkinson's disease, as they are associated with higher risk of morbidity, loss of functional ability, institutionalization, and mortality. Metabolic syndrome (MetS) is associated with poorer physical performance in middle age, but its impact in the older and frailer subjects is unclear. The present study aimed at assessing the association of MetS with falls in patients with Parkinson's disease. METHODS: We analyzed data of 194 elderly with Parkinson's disease attending a geriatric Day Hospital. History of falls that occurred over the last year, as well as and the number of falls, were recorded. Metabolic syndrome was diagnosed according to the National Cholesterol Education Program's ATP-III criteria. RESULTS: Falls were reported by 91 participants (47%). Logistic regression analysis showed that MetS was associated with reduced occurrence of falls (OR = .26; 95% CI = .10-.69; P = .007). Also, among participants who fell, Poisson regression indicated that MetS predicted a reduced number of falls (IRR = .43; 95% CI = .20-.89; P = .024). CONCLUSIONS: In our population MetS was associated with reduced probability of falls; among subjects who fell, MetS was associated with a reduced number of falls. Dedicated studies are needed to better understand the subsystems involved, as well as the therapeutic implications of such an association.

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The health status of older people is frequently complicated by one or more chronic diseases. Some conditions might have a different meaning in certain groups of elderly subjects, like in frail people or older patients with heart failure. Cut-off values defining these conditions may require adjustment in such groups. Indeed, several such conditions (e.g. obesity and hypercholesterolemia) have been discussed recently in light of so-called paradoxical situations, which are - counter-intuitively - associated with better outcome instead of a negative impact on survival in the general population. Therefore, different cut-off values may be needed in some groups of older subjects. The pathophysiological mechanisms for these paradoxical situations need to be understood in at least two different ways, causal and non-causal. The aim of this review is to provide an overview of a variety of conditions (obesity, dyslipidaemia, hypertension, and diabetes) in which new cut-offs may have diagnostic, clinical, or prognostic value, focusing on heart failure as a chronic disease, which is frequently observed in older patients. Haemoglobin concentration may need a different cut-off in heart failure for a reason other than paradox. Namely, underlying iron deficiency itself, both in those with or without anaemia, can have effects on symptoms and quality of life. Further studies will be needed for re-defining cut-off values in heart failure and maybe in the other chronic illnesses.

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OBJECTIVES: Previous prospective studies on ischemic stroke patients have shown conflicting results concerning the association between cholesterol level and patient outcome. We aimed to investigate the relation between cholesterol level and prior ischemic stroke. We hypothesized that acute ischemic stroke patients with increased cholesterol on admission more frequently had experienced prior ischemic stroke. METHODS: All consecutive patients with acute ischemic stroke (the index stroke) admitted to the Stroke Unit, Department of Neurology, Haukeland University Hospital between February 2006 and October 2013 were prospectively registered in The Bergen NORSTROKE Registry. On admission, cholesterol, low-density lipoprotein, and high-density lipoprotein levels were measured and prior ischemic stroke, risk factors, and medication were registered. Patients with prior versus no prior ischemic stroke were compared regarding risk factors, cholesterol levels, and use of statins on admission for the index stroke. Only patients with available cholesterol values measured on admission were included in the analyses. RESULTS: Of the 2,514 included patients admitted with acute ischemic stroke, 429 (17%) patients had prior ischemic stroke. We found a U-curve relationship between the relative frequency of prior ischemic stroke and cholesterol level. Lower frequency of prior ischemic stroke was associated with high cholesterol level on admission up to 5.5 mmol/L. For cholesterol levels higher than this, the opposite was true. These associations included all patients and statin-naive patients. For patients using statin there was a declining relative frequency of prior ischemic stroke from low to high cholesterol levels. CONCLUSION: Our hypothesis was falsified. The association between lower cholesterol levels and higher frequency of prior ischemic stroke in patients with cholesterol <5.5 mmol/L cannot be solely an effect of aggressive statin treatment in patients with prior ischemic stroke, as the association pertained also to patients who did not use statin.

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The prevalence of obesity is increasing at an epidemic rate globally with more than 1 billion adults overweight and at least 300 million of them clinically obese. This is expected to rise further in the next 20 to 30 years. Obesity is known to be an independent risk factor for serious health conditions, including hypertension, type 2 diabetes, and cardiovascular diseases. Given the association of obesity with cardiovascular disease, it could be speculated that obese individuals would have adverse outcomes after a cardiovascular event compared to those with normal body mass index (BMI). However, various studies have reported a paradoxical U-shaped relationship between obesity and mortality from various diseases, including myocardial infarction and heart failure, suggesting that patients with higher BMI have similar or lower short- and long-term mortality rates. This phenomenon has been termed the 'obesity paradox' or 'reverse epidemiology'. The goal of this review is to evaluate the potential mechanisms behind the obesity paradox and its implications.

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BACKGROUND: Plasma aldosterone is markedly increased in end stage renal disease (ESRD). The relationship between aldosterone, all-cause and cardiovascular (CV) mortality in observational studies performed so far is controversial. DESIGN: We investigated the relationship between aldosterone, mortality and CV events in multivariate analyses including nutrition status, inflammation, LV function and fluids volume biomarkers in 278 ESRD patients without heart failure at baseline. RESULTS: In univariate analyses aldosterone was an inverse predictor of death (3rd tertile vs. 1st tertile Hazard ratios (HR): 0·58; 95% confidence interval (CI) 0·38-0·90. P = 0·01) and CV events (HR: 0·63; 95% CI 0·41-0·96; P = 0·03). Data adjustment for inflammation and malnutrition biomarkers substantially reduced the inverse relationship between aldosterone, mortality and CV events to be largely not significant (P = 0·31 and P = 0·36, respectively). The same was true by adjusting for volume expansion and LV dysfunction (left atrial volume and atrial natriuretic peptide) biomarkers (P = 0·30 for both outcomes). In a model adjusting for the full set of biomarkers of protein energy wasting/inflammation and volume expansion/LV dysfunction the inverse relationship between aldosterone and death and CV events was nullified (HR for death 0·98, P = 0·93; HR for CV events 0·96, P = 0·87). CONCLUSIONS: Aldosterone is an inverse predictor of mortality and CV events in ESRD patients. This seemingly paradoxical relationship is abolished by statistical adjustment for inflammation, protein energy malnutrition, and volume expansion biomarkers indicating that it is the mere expression of the confounding effect of these factors. A clinical trial is needed to establish if aldosterone antagonism may improve clinical outcomes in ESRD.

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Traditional risk factors of cardiovascular death in the general population, including body mass index (BMI), serum cholesterol, and blood pressure (BP), are also found to relate to outcomes in the geriatric population, but in an opposite direction. Some degrees of elevated BMI, serum cholesterols, and BP are reportedly associated with lower, instead of higher, risk of death among the elderly. This phenomenon is termed "reverse epidemiology" or "risk factor paradox" (such as obesity paradox) and is also observed in a variety of chronic disease states such as end-stage renal disease requiring dialysis, chronic heart failure, rheumatoid arthritis, and AIDS. Several possible causes are hypothesized to explain this risk factor reversal: competing short-term and long-term killers, improved hemodynamic stability in the obese, adipokine protection against tumor necrosis factor-α, lipoprotein protection against endotoxins, and lipophilic toxin sequestration by the adipose tissue. It is possible that the current thresholds for intervention and goal levels for such traditional risk factors as BMI, serum cholesterol, and BP derived based on younger populations do not apply to the elderly, and that new levels for such risk factors should be developed for the elderly population. Reverse epidemiology of conventional cardiovascular risk factors may have a bearing on the management of the geriatric population, thus it deserves further attention.

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