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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the general population, a high body mass index (BMI; in kg/m(2)) is associated with increased cardiovascular disease and all-cause mortality. However, the effect of overweight (BMI: 25-30) or obesity (BMI: >30) in patients with chronic kidney disease (CKD) undergoing maintenance hemodialysis (MHD) is paradoxically in the opposite direction; ie, a high BMI is associated with improved survival. Although this "reverse epidemiology" of obesity or dialysis-risk-paradox is relatively consistent in MHD patients, studies in CKD patients undergoing peritoneal dialysis have yielded mixed results. Growing confusion has developed among physicians, some of whom are no longer confident about whether to treat obesity in CKD patients. A similar reverse epidemiology of obesity has been described in geriatric populations and in patients with chronic heart failure (CHF). Possible causes of the reverse epidemiology of obesity include a more stable hemodynamic status, alterations in circulating cytokines, unique neurohormonal constellations, endotoxin-lipoprotein interaction, reverse causation, survival bias, time discrepancies among competitive risk factors, and malnutrition-inflammation complex syndrome. Reverse epidemiology may have significant clinical implications in the management of dialysis, CHF, and geriatric patients, ie, populations with extraordinarily high mortality. Exploring the causes and consequences of the reverse epidemiology of obesity in dialysis patients can enhance our insights into similar paradoxes observed for other conventional risk factors, such as blood pressure and serum cholesterol and homocysteine concentrations, and in other populations such as those with CHF, advanced age, cancer, or AIDS. Weight-gaining interventional studies in dialysis patients are urgently needed to ascertain whether they can improve survival and quality of life.
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PMID:Survival advantages of obesity in dialysis patients. 1621 Jul 24

Cardiovascular risk is dramatically increased in patients with end-stage renal disease (ESRD). However, even minor dys-functions such as microalbuminuria or a mild increase in serum creatinine (Cr) have a major impact on cardiovascular risk. Increased cardiovascular risk is present in multiple populations, including general populations, patients with moderate risk such as hypertensives, and high-risk patients including patients with heart failure and myocardial necrosis. There are many mechanisms underpinning the increased cardiovascular risk. Regarding atherosclerosis, the kidney can be victim or villain. On the one hand, both kidney disease per se and renal insufficiency can induce vascular damage, thereby increasing cardiovascular risk. Kidney disease without renal insufficiency can cause an increased prevalence in hypertension, dyslipidemia (nephrotic syndrome), sympathetic system hyperactivity, and in renin angiotensin system hyperactivity. A moderate-severe renal insufficiency can induce an increase in many vasculotoxic substances such as ADMA, lipoprotein(a), homocysteine, disturbances in calcium and phosphate metabolism, anemia and left ventricular hypertrophy. A more severe renal insufficiency can induce the ominous malnutrition-inflammation-atherosclerosis (MIA) syndrome. On the other hand, the kidney can be the victim of atherosclerosis. Ischemic nephropathy, caused by atherosclerotic renal artery disease and atheroembolism from abdominal aorta are two examples. Finally, it is important to consider that the kidney, being an organ with a wide vasculature, could be a sophisticated sensor of subclinical cardiovascular damage.
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PMID:[Hypertension, atherosclerosis and kidney]. 1578 9

The aim was the study of the connection of the changes in serum homocysteine concentration with acute myocardium infarction, in order to establish whether the increase in homocysteine concentration is one of the risk-factors in the development of the cardiac insufficiency. The patients with acute myocardial infarction were studied. The following tests were performed: determination of the homocysteine concentration in serum by ELISA; determination of the main characteristics of hemostasis by automatic coagulometer (AMELUNG); determination of lipid spectrum by biochemical analyzer (Johnson & Johnson Vitros DT). The results obtained allowed us to suggest that the changes in the serum homocysteine concentration in patients with myocardial infarction occur in accordance with the changes in the protective mechanisms of the organism, and it may be used for the diagnostics of weakening and strengthening of the processes of arteriosclerosis and thrombosis.
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PMID:[Significance of homocysteines in the development of acute myocardial infarction]. 1590 29

Accumulation of interstitial collagen (fibrosis) between the endothelium and myocytes is one of the hallmarks of cardiac failure in renovascular hypertension (RVH). Renal insufficiency increases plasma homocysteine (Hcy), and levels of peroxisome proliferator-activated receptor-gamma (PPAR-gamma) are inversely related to plasma Hcy levels. We hypothesize that in RVH, accumulation of collagen between the endothelium and myocytes leads to endothelial-myocyte disconnection and uncoupling, in part, by hyperhomocysteinemia. Furthermore, we hypothesize that Hcy increases reactive oxygen species, generates nitrotyrosine, activates latent matrix metalloproteinase, and decreases the levels of endothelial nitric oxide in response to antagonizing PPAR-gamma. To create RVH in mice, the left renal artery was clipped with 0.4-mm silver wire for the 2 kidney, 1 clip (2K1C) method. Sham surgery was used as a control. To induce PPAR-gamma, 8 microg/mL ciglitazone (CZ) was administered to drinking water 2 days before surgery and continued for 4 weeks. Mice were grouped as 2K1C, sham, 2K1C+CZ, or sham+CZ (n = 6 in each group). Plasma Hcy increased 2-fold in the 2K1C-treated group (p < 0.05) as compared with the sham, and CZ had no effect on Hcy levels as compared to the 2K1C-treated group. Hcy binding in cardiac tissue homogenates decreased in the 2K1C-treated group but was substantially higher in the CZ-treated group. Cardiac reactive oxygen species levels were increased and endothelial nitric oxide were decreased in the 2K1C-treated group. Matrix metalloproteinase-2 and -9 activities were increased in the 2K1C-treated group compared with the control. Levels of cardiac inhibitor of metalloproteinase were decreased, whereas there was no change in tissue inhibitor of metalloproteinase-1 expression in the 2K1C-treated group vs. the sham-treated group. Collagen and nitrotyrosine levels were increased in the 2K1C-treated group, but mice treated with CZ showed lower levels comparatively. Cardiac transferase deoxyuridine nick-end labeling-positive cells were increased, and muscle cells were impaired in the 2K1C-treated mice vs. the sham-control mice. This was associated with decreased acetylcholine and bradykinin responses, which suggests endothelial-myocyte uncoupling in 2K1C-treated mice. Our results suggest that fibrosis between the endothelium and myocytes leads to an endothelial-myocyte disconnection and uncoupling by Hcy accumulation secondary to increased reactive oxygen species, nitrotyrosine, matrix metalloproteinase, and decreased endothelial nitric oxide in response to antagonizing PPAR-gamma.
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PMID:Homocysteine-dependent cardiac remodeling and endothelial-myocyte coupling in a 2 kidney, 1 clip Goldblatt hypertension mouse model. 1609 84

Formation of homocysteine (Hcy) is the constitutive process of gene methylation. Hcy is primarily synthesized by de-methylation of methionine, in which s-adenosyl-methionine (SAM) is converted to s-adenosyl-homocysteine (SAH) by methyltransferase (MT). SAH is then hydrolyzed to Hcy and adenosine by SAH-hydrolase (SAHH). The accumulation of Hcy leads to increased cellular oxidative stress in which mitochondrial thioredoxin, and peroxiredoxin are decreased and NADH oxidase activity is increased. In this process, Ca2+-dependent mitochondrial nitric oxide synthase (mtNOS) and calpain are induced which lead to cytoskeletal de-arrangement and cellular remodeling. This process generates peroxinitrite and nitrotyrosine in contractile proteins which causes vascular dysfunction. Chronic exposure to Hcy instigates endothelial and vascular dysfunction and increases vascular resistance causing systemic hypertension. To compensate, the heart increases its load which creates adverse cardiac remodeling in which the elastin/collagen ratio is reduced, causing cardiac stiffness and diastolic heart failure in hyperhomocysteinemia.
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PMID:Mitochondrial mechanism of oxidative stress and systemic hypertension in hyperhomocysteinemia. 1614 54

High plasma homocysteine levels are associated with a moderately increased risk of cardiovascular disease, particularly of atherosclerotic events. We review the association of plasma homocysteine with heart failure, with a specific focus on a series of previously published investigations from the community-based Framingham Heart Study that evaluated the relations of plasma homocysteine levels with overt heart failure, and with its key antecedents, echocardiographic left ventricular (LV) mass and hypertension. In the Framingham sample, higher plasma homocysteine levels were associated with increased risk of new-onset heart failure in both men and women, with a more continuous and graded relation being observed in women. A positive relation between homocysteine and LV mass was observed in women, but not in men; this may underlie the stronger relations of homocysteine to heart failure risk in women. Plasma homocysteine was not associated with hypertension incidence prospectively in either sex. The relations of increased homocysteine to heart failure (in both sexes) and to greater LV mass (in women) noted in the Framingham sample should be confirmed in other community-based samples. Secondary analyses of heart failure outcomes in ongoing randomized clinical trials may provide insights into whether lowering of plasma homocysteine levels is associated with a reduction in LV mass and/or a reduction of heart failure risk.
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PMID:Homocysteine and heart failure: a review of investigations from the Framingham Heart Study. 1619 86

We have previously shown that hyperhomocysteinaemia is common in elderly heart failure patients, and is associated with endothelial dysfunction, impaired vasodilatory capacity and a low-grade inflammation. In the present study we examined if supplementation with B6, B12 and folate could normalize the hyperhomocysteinaemia and if so, in turn, would improve the associated parameters. This was an open study without placebo control on heart failure patients with plasma homocysteine > 15 microM. Measurements of cutaneous vascular reactivity, blood pressure, inflammatory activity and endothelial function were performed before and after intervention with intra-individual comparisons. The treatment reduced homocysteine to near normal values and enhanced the hyperaemic response to acetylcholine related to the response to heat. The mean arterial blood pressure and pulse rate was reduced. There was no effect on inflammatory activity, plasma levels of von Willebrand factor, subjective health quality or the hyperaemic responses to sodium nitroprusside or local warming. Hyperhomocysteinaemia in heart failure patients is multifactorial in origin. Folate deficiency, inflammatory activity and reduced renal function could be contributing. It is suggested that supplementation with B-vitamins can improve the vasodilatory capacity and reduce the blood pressure but additional studies are required to confirm this.
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PMID:Reduction of homocysteine in elderly with heart failure improved vascular function and blood pressure control but did not affect inflammatory activity. 1623 43

Osteoporosis, chronic heart failure (CHF) and mild to moderate hyperhomocysteinemia (HHCY) can frequently be found in elderly individuals and often occur in the same individual. Due to demographic changes in the number of elderly people the total number of individuals suffering from osteoporosis and/or CHF, and hence the cost to society, will increase dramatically over the next 50 years. Thus, prevention of these diseases by identifying and modifying risk factors is a major issue. Recent large population-based prospective studies suggested HHCY as an independent risk factor for CHF and osteoporosis. However, the mechanisms that link HHCY to CHF and osteoporosis are almost unknown. Moreover, until now both diseases have been considered as independent diseases. The finding that heart and bones share a common biochemical risk factor raises the question if there is a biochemical link between these two diseases? This manuscript reviews the existing literature about HHCY and osteoporosis, about HHCY and CHF, and about possible mechanisms that link HHCY to both diseases. Existing data suggest that HHCY could be a useful paradigm with most interesting therapeutic implications, because HCY lowering therapy could favourably influence the course in CHF and osteoporotic patients.
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PMID:Hyperhomocysteinemia--the biochemical link between a weak heart and brittle bones? 1658 60

Serum homocysteine levels, which increase with age, are now recognized as a vascular risk factor and are related to the development of heart failure and dementia in the elderly. However, relatively low serum homocysteine levels have also been reported to be an adverse prognostic factor in dialysis patients. The objective of the study was to analyze the prevalence, clinical significance, and prognostic value of serum homocysteine levels in patients older than 65 years, admitted to a general internal medicine hospitalization unit. We studied 337 hospitalized patients, 184 males and 153 females, aged 77.2+/-0.4 years, whose admission was not determined by an acute vascular event. We recorded past vascular events and vascular risk factors. We determined the body mass index (weight in kilograms divided by the square of height in meters), and cholesterol, triglyceride, folate, vitamin B12, and homocysteine levels. We also studied 36 control subjects (18 males and 18 females) of similar age. After discharge, we assessed the survival status of 301 patients by telephone recall. Survival curves were plotted by the method of Kaplan and Meier. Median survival was 1186 days. The 15th (9.6 micromol/L) and 50th (14.4 micromol/L) percentiles, as the lowest and highest cut-off points, were empirically defined as those related to a shorter survival. Serum homocysteine concentration was significantly positively correlated with age and serum creatinine and albumin concentrations, and negatively correlated with serum cobalamin and folate concentrations. The average serum homocysteine concentration for the patients group, as a whole, was 16.5+/-0.5 micromol/L, not significantly different from the control group, but with a much greater dispersion, as patients with congestive heart failure or cognitive impairment had higher serum homocysteine concentrations, and patients with sepsis, leukocytosis, and hypoalbuminemia had lower concentrations. Malnutrition was associated both with abnormally high and low homocysteine concentrations, and abnormally low and abnormally high homocysteine concentrations were both associated with higher mortality. In conclusion, low homocysteine levels in elderly non-vitamin-supplemented hospitalized patients should not be interpreted as a protective factor in some individuals. Instead, it may be considered as an effect of an inflammatory-malnutrition process associated with a poor prognosis.
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PMID:Clinical significance of homocysteine in elderly hospitalized patients. 1663 38

Osteoprotegerin (OPG) is a member of the tumour necrosis factor superfamily and is involved in the regulation of bone metabolism and vascular calcification. Increased serum OPG levels have been reported in patients with stable angina pectoris and survivors of myocardial infarction with heart failure. The purpose of the present study was to determine serum OPG levels in young survivors of acute myocardial infarction (MI), and the relationship between OPG, homocysteine, sCD40L and coagulation factors in blood. Fifty-eight patients with verified MI, 40-60 years of age, were recruited 1-4 years after the acute event into an age- and sex- matched case control study with controls recruited from the general population. Serum OPG levels were similar in cases (2.41 ng/ml, 2.11-2.77 ng/ml) (mean, 95% CI) and controls (2.43 ng/ml, 2.11-2.79 ng/ml) (p = 0.92). Significant correlation between OPG and homocysteine was found in patients (r = 0.30, p = 0.02) and controls (r = 0.35, p = 0.007). A significant negative correlation was found between OPG and sCD40L in patients (r = -0.51, p < 0.001), but not in controls (r = 0.001, p = 0.96). No associations were found between serum OPG and markers of coagulation activation. The present study shows that serum OPG level was not increased in young survivors of uncomplicated myocardial infarction. Serum OPG levels were not associated with thrombin generation assessed by thrombin-antithrombin complexes (TAT), but a positive association between serum OPG and homocysteine was found.
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PMID:Serum osteoprotegerin in young survivors of myocardial infarction. 1667 81


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