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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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Correlations between ADMA and HDL circulating levels (r = −0.311, p<0.001).
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pone-0064796-g002: Correlations between ADMA and HDL circulating levels (r = −0.311, p<0.001).

Mentions: Spearman correlation analyses for ADMA, SDMA, L-arginine and biological parameters are reported in Table 3. ADMA was positively related to SDMA and L-arginine, with a trend towards a negative relationship with homocysteine (p = 0.067). Moreover, ADMA showed a strong negative correlation with HDL-C (r = −0.311, p<0.001) (Figure 2). SDMA had only a weak and positive association with HDL-C (p = 0.040), but a strong correlation with both LDL and homocysteine (p<0.001). L-arginine was associated positively with LDL and triglyceride levels, but negatively with HDL-C (p = 0.006). Subgroup correlation analysis showed that whatever the LDL and CRP levels (i.e. stratified by median values) and treatments (stratified by statin or fibrate use), the significant relationship between ADMA and HDL-C was maintained in all subgroups (p<0.001). In contrast, when patients were classified according to HDL-C levels (stratified by low/high HDL-C) (Table 4), only patients with low HDL-C levels showed a strong relationship between HDL-C and ADMA (r = −0.265, p<0.001). In contrast, there was no significant correlation between these two parameters in patients with higher HDL-C (p = 0.225).


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)

Correlations between ADMA and HDL circulating levels (r = −0.311, p<0.001).
© Copyright Policy
Related In: Results  -  Collection

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

pone-0064796-g002: Correlations between ADMA and HDL circulating levels (r = −0.311, p<0.001).
Mentions: Spearman correlation analyses for ADMA, SDMA, L-arginine and biological parameters are reported in Table 3. ADMA was positively related to SDMA and L-arginine, with a trend towards a negative relationship with homocysteine (p = 0.067). Moreover, ADMA showed a strong negative correlation with HDL-C (r = −0.311, p<0.001) (Figure 2). SDMA had only a weak and positive association with HDL-C (p = 0.040), but a strong correlation with both LDL and homocysteine (p<0.001). L-arginine was associated positively with LDL and triglyceride levels, but negatively with HDL-C (p = 0.006). Subgroup correlation analysis showed that whatever the LDL and CRP levels (i.e. stratified by median values) and treatments (stratified by statin or fibrate use), the significant relationship between ADMA and HDL-C was maintained in all subgroups (p<0.001). In contrast, when patients were classified according to HDL-C levels (stratified by low/high HDL-C) (Table 4), only patients with low HDL-C levels showed a strong relationship between HDL-C and ADMA (r = −0.265, p<0.001). In contrast, there was no significant correlation between these two parameters in patients with higher HDL-C (p = 0.225).

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