Prospective Study of Hyperhomocysteinemia as an Adverse Cardiovascular Risk Factor in End-Stage Renal Disease

Moustapha, Ali; Naso, Arabi; Nahlawi, Maher; Gupta, Anjan; Arheart, Kristopher L.; Jacobsen, Donald W.; Robinson, Killian; Dennis, Vincent W.

doi:10.1161/01.cir.97.2.138

Cited by 366 publications

(227 citation statements)

References 16 publications

(14 reference statements)

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“…Hyperhomocysteinemia is present in the vast majority of maintenance dialysis patients according to almost all descriptive and prevalent studies (5)(6)(7)(8)(9)(10)(11)(12). In most of such studies, including our current study, Ͼ90% of maintenance dialysis patients have hyperhomocysteinemia, and the mean and median values of tHcy are between 20 and 25 mol/L.…”

Section: Discussionsupporting

confidence: 50%

“…In maintenance hemodialysis (MHD) outpatients, however, the association between tHcy and clinical outcome is inconsistent and even paradoxical. Some studies have shown a poor outcome in MHD patients with hyperhomocysteinemia (5)(6)(7)(8)(9). However, a few recent studies have suggested that a decreased, not an increased, tHcy concentration is related to a higher prevalence of cardiovascular disease and poor outcome in these individuals (10 -12).…”

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confidence: 99%

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A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Kalantar-Zadeh

Block

Humphreys

et al. 2004

Journal of the American Society of Nephrology

153

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Abstract. An increased level of total plasma homocysteine (tHcy) is a risk factor for poor cardiovascular outcome in the general population. However, a decreased, rather than an increased, tHcy concentration may predict poor outcome in maintenance hemodialysis (MHD) patients, a phenomenon referred to as reverse epidemiology. Associations were examined between tHcy level and markers of malnutrition-inflammation complex syndrome and 12-mo prospective hospitalization and mortality in 367 MHD patients, aged 54.5 Ϯ 14.7 (mean Ϯ SD) years, who included 199 men and 55% individuals with diabetes. tHcy was 24.4 Ϯ 11.8 mol/L, and 94% of the patients had hyperhomocysteinemia (tHcy Ͼ13.5 mol/L). tHcy had weak to moderate but statistically significant bivariate and multivariate correlations with some laboratory markers of nutrition (serum albumin, prealbumin, creatinine, and urea nitrogen) but no significant correlation with serum C-reactive protein or two proinflammatory cytokines (IL-6 and TNF-␣).During 12 mo of follow-up, 191 MHD patients were hospitalized, 37 died, nine underwent renal transplantation, and 38 transferred out. Hospitalization rates were significantly higher in patients with lower tHcy levels. Mortality rate in the lowest tHcy quartile (17.4%) was significantly higher compared with other three quartiles (6.5 to 9.8%; Kaplan-Meier P ϭ 0.04). Relative risk of death for the lowest tHcy quartile, even after adjustment for case-mix and serum albumin, was 2.27 (95% confidence interval, 1.14 to 4.53; P ϭ 0.02). Hence, tHcy may be a more exclusive nutritional marker in MHD patients with no association with inflammatory measures. Despite a very high prevalence of hyperhomocysteinemia in MHD patients, lower values of tHcy are paradoxically associated with increased hospitalization and mortality. The lowest tHcy quartile confers a twofold increase in risk of death independent of hypoalbuminemia. The nutritional feature of tHcy in MHD patients may explain its reverse association with outcome.In the general population, an increased level of total plasma homocysteine (tHcy) is a risk factor for increased cardiovascular events and mortality (1-4). In maintenance hemodialysis (MHD) outpatients, however, the association between tHcy and clinical outcome is inconsistent and even paradoxical. Some studies have shown a poor outcome in MHD patients with hyperhomocysteinemia (5-9). However, a few recent studies have suggested that a decreased, not an increased, tHcy concentration is related to a higher prevalence of cardiovascular disease and poor outcome in these individuals (10 -12). This seems to be due to the empirical association between a low tHcy and protein-energy malnutrition, which is per se a known risk factor for poor clinical outcome in dialysis patients (11,13,14). This recently described paradoxical association between tHcy and clinical outcome in dialysis patients has now been referred to as a possible component of the reversal of the cardiovascular risks (15-17). It is believed that both inflammation and protei...

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Section: Discussionsupporting

confidence: 50%

mentioning

confidence: 99%

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Kalantar-Zadeh

Block

Humphreys

et al. 2004

Journal of the American Society of Nephrology

153

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“…8,10,12 A smaller literature in renal transplantation also points a substantial risk of hyperhomocysteinemia contributing to the increased risk of early cardiovascular disease. [17][18][19][20][21] Whereas small retrospective studies are often subject to various biases, prospective studies generally provide a more robust estimate of association.…”

Section: Discussionmentioning

confidence: 99%

“…5,6 Prospective studies of patient populations known to be at high risk of cardiovascular events, including renal patients, consistently report strong associations between homocysteine and cardiovascular as well as all-cause mortality. [7][8][9][10][11][12][13][14][15][16] Elevated levels of fasting total plasma homocysteine (tHcy) are prevalent in patients who underwent kidney …”

mentioning

confidence: 99%

Impact of Homocysteinemia on Long-Term Renal Transplant Survival

Fonseca

Martins

Queirós

et al. 2005

Transplantation Proceedings

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Aim. We prospectively followed a cohort of 202 renal transplant recipients for 5 years to examine the impact of fasting homocysteinemia on long-term patient and renal allograft survival. Methods. Cox proportional hazards regression analysis was used to identify independent predictors of all-cause mortality and graft loss. Results. Hyperhomocysteinemia (tHcy Ͼ15 mol/L) was present in 48.7% of the 202 patients, predominantly among men (55.8%) as opposed to women (37.1%). At the end of the follow-up period, 13 (6.4%) patients had died including 10 from cardiovascular disease, and 23 had (11.4%) had lost their grafts. Patient death with a functioning allograft was the most prevalent cause of graft loss (13 recipients). Levels of tHcy were higher among patients who died than among survivors (median 23.9 vs 14.3 mol/L; P ϭ .005). Median tHcy concentration was also higher among the patients who had lost their allografts than those who did not (median 19.0 vs 14.1 mol/L; P ϭ .001). In a Cox regression model including gender, serum creatinine concentration, transplant duration, traditional cardiovascular risk factors, and associated conditions, such as past cardiovascular disease, only tHcy concentration (ln) (HR ϭ 5.50; 95% CI, 1.56 to 19.36; P ϭ .008) and age at transplantation (HR ϭ 1.07; 95% CI, 1.02 to 1.13; P ϭ .01) were independent predictors of patient survival. After censoring data for patient death, tHcy concentration was not a risk factor for graft loss.Conclusions. This prospective study shows that tHcy concentration is a significant predictor of mortality, but not of graft loss, after censoring data for patient death.S HORT-AND LONG-TERM GRAFT and patient survivals after renal transplantation have improved considerably over the past three decades. However, life expectancy beyond 10 years is still considerably less than in the general population, mainly due to cardiovascular events. In fact, an accelerated form of atherosclerosis commonly occurs in these patients. Cardiovascular disease is the leading cause of morbidity and mortality in renal transplant recipients, accounting for approximately 40% of all deaths. 1,2 Classic cardiovascular risk factors (eg, dyslipidemia, hypertension, and diabetes) as well as nonmodifiable risk factors such as age, gender, and family history do not fully explain the cardiovascular disease. Among other predictors of atherosclerotic disease, attention has been drawn to the association between homocysteine and cardiovascular events. Clinical and epidemiological studies have shown that homocysteine measured in serum or plasma is a strong predictor of cardiovascular risk. 3,4 The results of early cross-sectional and case-control studies strongly support this hypothesis. 5,6 Prospective studies of patient populations known to be at high risk of cardiovascular events, including renal patients, consistently report strong associations between homocysteine and cardiovascular as well as all-cause mortality. [7][8][9][10][11][12][13][14][15][16] Elevated levels of fasting total ...

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“…Quatre études récentes chez des hémodialysés suggèrent que l'hyperhomocystéinémie est un facteur de risque indépen-dant de complications athérothrombotiques fatales ou non [22,25]. Cependant, le traitement de l'hyperhomocystéinémie reste controversé, puisqu'aucune étude n'a pu montrer qu'une correction des niveaux d'homocystéine améliorait le risque cardiovasculaire.…”

Section: Autres Facteursunclassified

Facteurs de risque vasculaire et insuffisance rénale

Madore

2004

Med Sci (Paris)

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Prospective Study of Hyperhomocysteinemia as an Adverse Cardiovascular Risk Factor in End-Stage Renal Disease

Cited by 366 publications

References 16 publications

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

A Low, Rather than a High, Total Plasma Homocysteine Is an Indicator of Poor Outcome in Hemodialysis Patients

Impact of Homocysteinemia on Long-Term Renal Transplant Survival

Facteurs de risque vasculaire et insuffisance rénale

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