Coronary endothelial function: The impact of aging in a matched study group with normal coronary arteries

Aims: Inflammation plays a critical role in the pathogenesis of coronary artery disease (CAD), however the impact of anti-inflammatory therapies to reduce those processes which promote atherosclerosis in CAD patients is unknown. We aimed to test the hypothesis that anti-inflammatory approaches improve impaired coronary endothelial function (CEF), a driver of coronary atherosclerosis, in stable CAD patients.Methods and Results: We performed a single-center, randomized, placebo-controlled, double-blinded trial to assess whether low dose methotrexate (MTX), low dose colchicine (LDC), and/or their combination (MTX+LDC), improves CEF using non-invasive MRI measures in patients with stable CAD (N = 94). The primary endpoint was the MRI-detected change in coronary cross-sectional area from rest to isometric handgrip exercise (IHE), a predominantly nitric oxide-dependent endothelial dependent stressor. Coronary and systemic endothelial endpoints, and serum inflammatory markers, were collected at baseline, 8 and 24 weeks. Anti-inflammatory study drugs were well-tolerated. There were no significant differences in any of the CEF parameters among the four groups (MTX, LDC, MTX+LDC, placebo) at 8 or 24 weeks. Serum markers of inflammation and systemic endothelial function measures were also not significantly different among the groups.Conclusion: This is the first study to examine the effects of the anti-inflammatory approaches using MTX, LDC, and/or the combination in stable CAD patients on CEF, a marker of vascular health and the primary endpoint of the study. Although these anti-inflammatory approaches were relatively well-tolerated, they did not improve coronary endothelial function in patients with stable CAD.Clinical Trial Registration:www.clinicaltrials.gov, identifier: NCT02366091.

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P1157 Long-term L-arginine therapy improves endothelial function assessed by a brachial artery vasoreactivity testing in patients with normal coronary arteries

European Heart Journal ◽

10.1016/s0195-668x(03)94449-6 ◽

2003 ◽

Vol 24 (5) ◽

pp. 214

Author(s):

M SHECHTER

Keyword(s):

Endothelial Function ◽

Coronary Arteries ◽

Brachial Artery ◽

Normal Coronary Arteries

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Abstract 3457: Methylenetetrahydrofolate Reductase Gene Polymorphism C677T And The Risk Of Premature Myocardial Infarction With “Normal” Coronary Arteries.

Circulation ◽

10.1161/circ.116.suppl_16.ii_781-d ◽

2007 ◽

Vol 116 (suppl_16) ◽

Author(s):

Loukianos Rallidis ◽

Christoforos Komborozos ◽

Argyri Gialeraki ◽

Maria Zolindaki ◽

Panagiotis Vavoulis ◽

...

Keyword(s):

Myocardial Infarction ◽

Coronary Arteries ◽

Methylenetetrahydrofolate Reductase ◽

Young Patients ◽

Mthfr C677t ◽

C677t Polymorphism ◽

Mthfr C677t Polymorphism ◽

Normal Coronary Arteries ◽

Methylenetetrahydrofolate Reductase Gene Polymorphism ◽

The Impact

Purpose: the pathogenetic mechanism of acute myocardial infarction (AMI) in young patients remains unknown. We explored the impact of homocysteine and its main genetic modulator Table 2 methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients who sustained AMI under the age of 36 years. Methods: we recruited 136 consecutive patients who had survived their first AMI before the age of 36 years (mean age=32 ± 3.1 years, range 23–35 years, 121 men). Blood was taken for lipids and homocysteine levels within 12 hours from admission. The MTHFR C677T polymorphism was also determined with polymerase chain reaction. All patients underwent cardiac catheterization. One hundred-three healthy individuals without a family history of coronary heart disease (CHD), matched for age and sex served as controls. Results: coronary angiogram revealed significant CHD in 104 patients while 32 (23.5%) had no significant CHD. The prevalence of homozygotes for C677T polymorphism [T/T genotype] was 27.2% in patients and 14.6% in controls (p=0.02). In the subgroup of patients who had AMI and “normal” coronary arteries the frequency of homozygotes was 43.8% (p=0.001 versus controls and p=0.02 versus patients with significant CHD). The table presents lipids and homocysteine levels in AMI patients with “normal” coronary arteries and controls. Logistic regression model showed that the odds ratio for a young individual with T/T genotype to develop AMI with “normal” coronary arteries was 5.2 (confidence interval 1.2–23, p=0.03) adjusted for smoking habits, body mass index, hypertension and diabetes mellitus. Conclusions: the presence of homozygocity for MTHFR C677T polymorphism is associated with 5-fold higher risk for premature AMI with “normal” coronary arteries. This suggests that homocysteine may be involved in the formation of an obstructive thrombus in coronary arteries, especially in young individuals without significant underlying atheromatic burden.

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The Impact of Gender on Vessel Size in Patients with Angiographically Normal Coronary Arteries

Journal of Interventional Cardiology ◽

10.1111/j.1540-8183.2006.00157.x ◽

2006 ◽

Vol 19 (4) ◽

pp. 340-344 ◽

Cited By ~ 29

Author(s):

FELIX YANG ◽

ROBERT M. MINUTELLO ◽

SHERRITA BHAGAN ◽

ATUL SHARMA ◽

S. CHIU WONG

Keyword(s):

Coronary Arteries ◽

Vessel Size ◽

Normal Coronary Arteries ◽

The Impact

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eNOS Gene Variants and the Risk of Premature Myocardial Infarction

Disease Markers ◽

10.1155/2013/235056 ◽

2013 ◽

Vol 34 (6) ◽

pp. 431-436 ◽

Cited By ~ 10

Author(s):

Aggeliki-Maria Zigra ◽

Loukianos S. Rallidis ◽

Georgia Anastasiou ◽

Efrossyni Merkouri ◽

Argyri Gialeraki

Keyword(s):

Nitric Oxide ◽

Myocardial Infarction ◽

Genetic Polymorphisms ◽

Coronary Arteries ◽

Significant Coronary Artery Disease ◽

Enos Gene ◽

Normal Coronary Arteries ◽

Premature Myocardial Infarction ◽

Artery Disease ◽

The Impact

BACKGROUND: Endothelial nitric oxide synthase (eNOS) as well as nitric oxide play an important role in the regulation of cardiovascular function. There are limited and controversial data regarding the impact of polymorphisms of eNOS gene that is implicated in the vasoconstrictive properties of the endothelium in the pathogenesis of premature myocardial infarction (MI).OBJECTIVE: We examined whether two common polymorphisms of eNOS gene (G894T and T786C) are associated with the development of premature MI.METHODS: We recruited 107 patients with premature MI and compared them to 103 age- and sex- matched controls. All patients underwent coronary angiogram and were classified into the subgroup of patients with ‘normal’ or ‘near normal’ coronary arteries and the subgroup of patients with significant coronary artery disease (≥ 50% stenosis in lumen diameter of coronary arteries). The genetic polymorphisms of eNOS gene were assayed with polymerase chain reaction and reverse hybridization.RESULTS: Nineteen patients (17.8%) had ‘normal’ or ‘near normal’ coronary arteries. A significantly higher frequency of homozygosity for the 786C (32%) and the 894T (21%) alleles of the eNOS gene in patients who develop early MI in the setting of angiographically 'normal' or 'near normal' coronary arteries were found.CONCLUSIONS: Our data suggest that the T786C and the G894T genetic polymorphisms are associated with the development of MI in very young individuals, whose coronary arteries are characterized by very small atheromatic burden.

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Syndrome X: a discussion of angina and normal coronary arteries

American Journal of Critical Care ◽

10.4037/ajcc1996.5.2.99 ◽

1996 ◽

Vol 5 (2) ◽

pp. 99-101 ◽

Cited By ~ 1

Author(s):

KA Zell ◽

SE Reis

Keyword(s):

Myocardial Infarction ◽

Endothelial Function ◽

Female Patient ◽

Coronary Flow Reserve ◽

Coronary Arteries ◽

Coronary Flow ◽

Single Case ◽

Syndrome X ◽

Normal Coronary Arteries ◽

Flow Reserve

Syndrome X was diagnosed in a female patient who presented with typical angina and a non-Q wave myocardial infarction, yet demonstrated normal coronary arteries. Syndrome X has been described as an impairment in normal endothelial function of the coronary microvasculature, resulting in inappropriate vasoconstriction and inadequate coronary flow reserve. In this article we review pathophysiology, diagnosis, treatment, and prognosis in a single case.

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