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High levels of asymmetric dimethylarginine are strongly associated with low HDL in patients with acute myocardial infarction.

Lorin J, Guilland JC, Korandji C, Touzery C, Bichat F, Chagnon A, Cottin Y, Rochette L, Vergely C, Zeller M - PLoS ONE (2013)

Bottom Line: In stratified analysis, this relationship was only found for low HDL levels (r = -0.265, p<0.001), but not when HDL levels were higher (r = -0.077, p = 0.225).By multivariate logistic regression analysis, ADMA level was strongly associated with low HDL levels (OR(95%CI):6.06(3.48-10.53), p<0.001), beyond traditional confounding factors.Our large population-based study showed for the first time a strong inverse relationship between HDL and ADMA in myocardial infarction patients, suggesting a functional interaction between HDL and endothelium, beyond metabolic conditions associated with low HDL levels.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMR866- Laboratory of Cardiometabolic Physiopathology and Pharmacology, University of Burgundy, Dijon, France.

ABSTRACT

Objectives: Low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of acute myocardial infarction possibly through impaired endothelial atheroprotection and decreased nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA) mediates endothelial function by inhibiting nitric oxide synthase activity. In patients with acute myocardial infarction, we investigated the relationship between serum levels of HDL and ADMA.

Approach and results: Blood samples from 612 consecutive patients hospitalized for acute MI <24 hours after symptom onset were taken on admission. Serum levels of ADMA, its stereoisomer, symmetric dimethylarginine (SDMA) and L-arginine were determined using high-performance liquid chromatography. Patients with low HDL (<40 mg/dL for men and <50 mg/dL for women) were compared with patients with higher HDL. Most patients (59%) had low HDL levels. Median ADMA levels were markedly higher in the low HDL group (0.69 vs. 0.50 µmole/L, p<0.001). In contrast, SDMA and L-arginine levels were similar for the two groups (p = 0.120 and p = 0.064). Notably, ADMA, but not SDMA or L-arginine, was inversely correlated with HDL (r = -0.311, p<0.001). In stratified analysis, this relationship was only found for low HDL levels (r = -0.265, p<0.001), but not when HDL levels were higher (r = -0.077, p = 0.225). By multivariate logistic regression analysis, ADMA level was strongly associated with low HDL levels (OR(95%CI):6.06(3.48-10.53), p<0.001), beyond traditional confounding factors.

Conclusions: Our large population-based study showed for the first time a strong inverse relationship between HDL and ADMA in myocardial infarction patients, suggesting a functional interaction between HDL and endothelium, beyond metabolic conditions associated with low HDL levels.

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Related in: MedlinePlus

L-arginine and dimethylarginines concentrations in patients according to their HDL levels.The horizontal line is the median, box is the IQR (interquartile range) and whiskers are the 95% range. P values are from Mann-Whitney tests.
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pone-0064796-g001: L-arginine and dimethylarginines concentrations in patients according to their HDL levels.The horizontal line is the median, box is the IQR (interquartile range) and whiskers are the 95% range. P values are from Mann-Whitney tests.

Mentions: Patients’ characteristics are shown in Table 1. Most patients (362/612 (59%)) had low HDL-C levels. Patients with low HDL-C were younger, more frequently smokers, with prior MI, had a higher body mass index, and showed a trend towards a greater rate of diabetes than patients with high HDL-C. Clinical data and current medications were similar for the two groups, except for fibrate therapy, which was more frequent in the low HDL-C group. Biological data are shown in Table 2. Higher CRP and triglycerides and a trend toward higher HbA1c levels were found in patients with low HDL-C. No difference was observed between the two groups for LDL-C, glucose, creatinine clearance and homocysteine. Interestingly, median ADMA concentrations were markedly higher (∼ 40%, i.e. 0.69 vs. 0.50 µmole/L, p<0.001) in patients with low HDL-C than in those with higher HDL-C levels (Figure 1). In contrast, there was no or only weak difference between the two groups for SDMA and L-arginine levels (p = 0.120 and p = 0.064, respectively).


High levels of asymmetric dimethylarginine are strongly associated with low HDL in patients with acute myocardial infarction.

Lorin J, Guilland JC, Korandji C, Touzery C, Bichat F, Chagnon A, Cottin Y, Rochette L, Vergely C, Zeller M - PLoS ONE (2013)

L-arginine and dimethylarginines concentrations in patients according to their HDL levels.The horizontal line is the median, box is the IQR (interquartile range) and whiskers are the 95% range. P values are from Mann-Whitney tests.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3675048&req=5

pone-0064796-g001: L-arginine and dimethylarginines concentrations in patients according to their HDL levels.The horizontal line is the median, box is the IQR (interquartile range) and whiskers are the 95% range. P values are from Mann-Whitney tests.
Mentions: Patients’ characteristics are shown in Table 1. Most patients (362/612 (59%)) had low HDL-C levels. Patients with low HDL-C were younger, more frequently smokers, with prior MI, had a higher body mass index, and showed a trend towards a greater rate of diabetes than patients with high HDL-C. Clinical data and current medications were similar for the two groups, except for fibrate therapy, which was more frequent in the low HDL-C group. Biological data are shown in Table 2. Higher CRP and triglycerides and a trend toward higher HbA1c levels were found in patients with low HDL-C. No difference was observed between the two groups for LDL-C, glucose, creatinine clearance and homocysteine. Interestingly, median ADMA concentrations were markedly higher (∼ 40%, i.e. 0.69 vs. 0.50 µmole/L, p<0.001) in patients with low HDL-C than in those with higher HDL-C levels (Figure 1). In contrast, there was no or only weak difference between the two groups for SDMA and L-arginine levels (p = 0.120 and p = 0.064, respectively).

Bottom Line: In stratified analysis, this relationship was only found for low HDL levels (r = -0.265, p<0.001), but not when HDL levels were higher (r = -0.077, p = 0.225).By multivariate logistic regression analysis, ADMA level was strongly associated with low HDL levels (OR(95%CI):6.06(3.48-10.53), p<0.001), beyond traditional confounding factors.Our large population-based study showed for the first time a strong inverse relationship between HDL and ADMA in myocardial infarction patients, suggesting a functional interaction between HDL and endothelium, beyond metabolic conditions associated with low HDL levels.

View Article: PubMed Central - PubMed

Affiliation: INSERM UMR866- Laboratory of Cardiometabolic Physiopathology and Pharmacology, University of Burgundy, Dijon, France.

ABSTRACT

Objectives: Low levels of high-density lipoprotein (HDL) cholesterol are associated with an increased risk of acute myocardial infarction possibly through impaired endothelial atheroprotection and decreased nitric oxide (NO) bioavailability. Asymmetric dimethylarginine (ADMA) mediates endothelial function by inhibiting nitric oxide synthase activity. In patients with acute myocardial infarction, we investigated the relationship between serum levels of HDL and ADMA.

Approach and results: Blood samples from 612 consecutive patients hospitalized for acute MI <24 hours after symptom onset were taken on admission. Serum levels of ADMA, its stereoisomer, symmetric dimethylarginine (SDMA) and L-arginine were determined using high-performance liquid chromatography. Patients with low HDL (<40 mg/dL for men and <50 mg/dL for women) were compared with patients with higher HDL. Most patients (59%) had low HDL levels. Median ADMA levels were markedly higher in the low HDL group (0.69 vs. 0.50 µmole/L, p<0.001). In contrast, SDMA and L-arginine levels were similar for the two groups (p = 0.120 and p = 0.064). Notably, ADMA, but not SDMA or L-arginine, was inversely correlated with HDL (r = -0.311, p<0.001). In stratified analysis, this relationship was only found for low HDL levels (r = -0.265, p<0.001), but not when HDL levels were higher (r = -0.077, p = 0.225). By multivariate logistic regression analysis, ADMA level was strongly associated with low HDL levels (OR(95%CI):6.06(3.48-10.53), p<0.001), beyond traditional confounding factors.

Conclusions: Our large population-based study showed for the first time a strong inverse relationship between HDL and ADMA in myocardial infarction patients, suggesting a functional interaction between HDL and endothelium, beyond metabolic conditions associated with low HDL levels.

Show MeSH
Related in: MedlinePlus