Relations between markers of renal function, coronary risk factors and the occurrence and severity of coronary artery disease

Wang, Jun; Sim, Ah Siew; Wang, Xing Li; Salonikas, Chris; Moriatis, Mary; Naidoo, Daya; Wilcken, D. E. L.

doi:10.1016/j.atherosclerosis.2007.07.034

Cited by 49 publications

(44 citation statements)

References 29 publications

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“…Our data are consistent with recent evidence that cystatin C is a sensitive indicator for the presence and severity of coronary artery disease and a predictor of vascular events. 5,33 However, we also found that cystatin C was not an independent predictor of CIMT and the reason for the discrepancy is not clear. Given the limitations discussed above, the relatively small subject numbers and the specificity of regression results to a particular data set, it is possible that either the FMD or CIMT regression results are attributable to chance.…”

Section: Discussioncontrasting

confidence: 56%

Homocysteine or Renal Impairment

Potter

Hankey

Green

et al. 2008

ATVB

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Objective-The purpose of this study was to determine whether adjustment for renal function eliminates the relationship between total plasma homocysteine (tHcy) and vascular risk, assessed by carotid intima medial thickness (CIMT) and flow-mediated dilation (FMD) of the brachial artery. Methods and Results-We used cross-sectional data from 173 stroke patients treated with B-vitamins (folic acid 2 mg, vitamin B 6 25 mg, and vitamin B 12 0.5 mg) or placebo in a randomized double-blinded trial to test the relationships between posttreatment tHcy, cystatin C (a marker of glomerular filtration rate), estimated glomerular filtration rate (eGFR, Modification of Diet in Renal Disease equation) creatinine, CIMT, and FMD in stepwise and multivariable regression models. The strong linear relationship between tHcy and cystatin C was not altered by long-term B-vitamin treatment. tHcy lost significance as a predictor of the vascular measurements after adjustment for any single marker of renal function. Cystatin C, but not tHcy, was a significant independent predictor of FMD after adjustment for age, sex, smoking, systolic blood pressure, high-density lipoprotein cholesterol, and treatment group. Conclusions-Adjusting for renal function eliminates the relationship between tHcy and CIMT and FMD, supporting the hypothesis that elevated tHcy is a marker for renal impairment rather than an independent cardiovascular risk factor. Key Words: homocysteine Ⅲ cystatin c Ⅲ stroke Ⅲ flow-mediated dilation Ⅲ carotid intima-medial thickness E levated plasma homocysteine concentrations (tHcy) are associated with an increased risk of stroke and myocardial infarction, but it remains unclear whether elevated tHcy causes atherosclerosis or is a marker of risk burden. Glomerular filtration rate (GFR) is the strongest determinant of tHcy in individuals with an adequate B-vitamin intake, and it has been suggested that elevated tHcy may account for some of the excess cardiovascular risk associated with renal failure. 1 Evidence that homocysteine-lowering treatment does not reduce vascular event rates or mortality in people with renal insuffiency has undermined this hypothesis. [2][3][4] See accompanying article on page 1031Recent data from 2 large prospective trials indicate that small reductions in GFR increase cardiovascular risk more significantly than previously appreciated, supporting the alternative hypothesis that renal impairment is an independent causal risk factor for atherosclerosis and mildly elevated tHcy a marker for reduced GFR. [5][6][7] Observational studies reporting an association between tHcy and surrogate markers of vascular risk, such as carotid intima medial thickness (CIMT) and flow-mediated dilation (FMD), frequently fail to adjust for renal function or correct only for creatinine. 8,9 Serum creatinine is influenced by many factors and is thus a relatively insensitive marker for renal insufficiency. Cystatin C is a more accurate indicator of GFR than creatinine, particularly in the elderly, as its concentration is not subst...

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Section: Discussioncontrasting

confidence: 56%

Homocysteine or Renal Impairment

Potter

Hankey

Green

et al. 2008

ATVB

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“…Multiple mechanisms have been postulated potentially explaining the association between renal dysfunction and CAD including endothelial dysfunction, enhanced oxidative stress and reduction of anti-inflammatory cytokines. Our data are also in agreement with the results of Wang et al [14] who showed that in patients with CAD and mild renal impairment, plasma cystatin C was most predictive of both occurrence and severity of CAD. Our data are in line with previous reports indicating that in a large group of patients with and without CAD and even mild renal impairment, elevated serum cystatin C levels were significantly associated with traditional vascular risk factors including homocysteine and hsCRP.…”

Section: Discussionsupporting

confidence: 83%

Reduced Kidney Function Estimated by Cystatin C and Clinical Outcomes in Hypertensive Patients with Coronary Artery Disease: Association with Homocysteine and Other Cardiovascular Risk Factors

Dzielińska

Januszewicz

Wiȩcek

et al. 2010

Kidney Blood Press Res

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Aims: To evaluate the association between serum cystatin C and homocysteine concentrations, cardiovascular risk factors and cardiovascular events in hypertensive patients with coronary artery disease (CAD). Methods: 260 patients with hypertension and CAD (mean age 56.9 ± 9.3) were included. During a mean 40-month follow-up the combined end-point of death from all causes, non-fatal myocardial infarction and stroke or coronary revascularization was assessed. Results: Subjects in the highest serum cystatin C quartile (>103.4 nmol/l) as compared with the lowest were older, were characterized by a higher frequency of multivessel CAD, higher levels of homocysteine (13.2 ± 5.2 vs. 11.4 ± 4.2 µmol/l; p < 0.01), fibrinogen and high-sensitivity C-reactive protein and by an increased intima-media thickness. Combined end-point occurred twice as frequently in the 4th quartile of serum cystatin C as compared with the 1st quartile (10.8 vs. 20.3%; p = 0.11). In an univariate analysis, but not in a multivariate model, cystatin C concentration predicted the combined end-point (Exp(B) = 1.096; p < 0.05). Conclusion: In hypertensive patients with CAD, serum cystatin C level was independently associated with the extent of CAD, homocysteine plasma level and traditional vascular risk factors. However, serum cystatin C concentration did not independently predict the combined end-point.

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“…One study showed a direct relation between renal function and ADMA levels [32]. However, 2 studies that investigated the circadian rhythm in creatinine in different populations and in different age groups [33,34] found a creatinine peak in the late afternoon or early evening, between 18:00 h and 19:00 h. It is thus out of phase with our reported rhythm in ADMA.…”

Section: Discussioncontrasting

confidence: 46%

Asymmetric Dimethylarginine (ADMA) Levels Display a Morning Peak in Patients with Acute Myocardial Infarction

et al. 2011

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Abstract. High Asymmetric Dimethylarginine (ADMA) levels are associated with increased platelet activity, elevated blood pressure, vasoconstriction and impaired vascular relaxation. We hypothesized that the myocardial infarction morning peak of occurrence is closely related to a morning peak of ADMA levels. We performed a cross-sectional study among patients with documented myocardial infarction who had been enrolled in the prospective MISSION! Intervention Study. In total, serum ADMA levels were measured in their acute setting of myocardial infarction in 120 patients. The frequency of myocardial infarction onset of symptoms and emergency coronary catheterization and the ADMA levels displayed a similar daily pattern with a morning peak between 06:00-11:59 h. The absolute ADMA levels peak was between 06:00-07:59 h with a median (interquartile range) peak value of 1.01 (0.84-1.21) µmol/L for the n = 9 patients vs. 0.75 (0.61-0.89) µmol/L for the remaining 111 patients admitted throughout the rest of the 24-hour interval (p = 0.003 for between groups comparison). The amplitude (95% confidence interval) of the circadian variation of ADMA levels was 0.08 µmol/L (0.004-0.16) with p = 0.042 for statistic model significance. In conclusion, ADMA levels display a 24-hour variation with a significant morning peak in patients with acute myocardial infarction. These findings may relate ADMA levels to the acute onset of thrombotic cardiovascular events.

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Relations between markers of renal function, coronary risk factors and the occurrence and severity of coronary artery disease

Cited by 49 publications

References 29 publications

Homocysteine or Renal Impairment

Homocysteine or Renal Impairment

Reduced Kidney Function Estimated by Cystatin C and Clinical Outcomes in Hypertensive Patients with Coronary Artery Disease: Association with Homocysteine and Other Cardiovascular Risk Factors

Asymmetric Dimethylarginine (ADMA) Levels Display a Morning Peak in Patients with Acute Myocardial Infarction

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