Coronary Endothelial Dysfunction In Patients Research Articles

A Systematic Review of CD34+ Stem Cell Therapy as an Innovative and Efficient Treatment for the Management of Refractory Angina.

Despite optimal medical treatment, many individuals suffering from severe coronary artery disease are not suitable candidates for further revascularization. Therapeutic angiogenesis has attracted continuous interest to increase myocardial perfusion. Cell therapy using autologous stem cells expressing Cluster of Differentiation 34 plus (CD34+) offers a special therapeutic choice for individuals with refractory angina, seeing as CD34+ stem cells can restore microcirculation. We searched PubMed, PubMed Central (PMC), and Google Scholar to find the relevant articles to write this systematic review about the role of CD34+ stem cell therapy in the management of refractory angina. Additionally, we provided a brief explanation of CD34+ cells and their mechanism of action. Along with the positive finding of other trials, a recent open-label, single-center intracoronary CD34+ cell therapy for the treatment of coronary endothelial dysfunction in patients with angina and nonobstructive coronary arteries (IMPROvE-CED) clinical trial published in 2022 concluded improvement in coronary blood flow, a significant reduction in daily as-needed sublingual nitroglycerin use and improvement in Canadian Cardiovascular Society (CCS) angina class were observed after autologous CD34+ cell treatment. In conclusion, refractory angina management and overall prognosis may be revolutionized once this treatment is approved.

Randomized Trial of Anti-inflammatory Medications and Coronary Endothelial Dysfunction in Patients With Stable Coronary Disease.

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.

Abstract 458: Chronic Inhibition of Protein Kinase C Improves Coronary Endothelial Function in the Setting of Diabetes and Hypoxia

Background: Both Diabetes (DM) and hypoxia/re-oxygenation (H/R) upregulate protein kinase C (PKC), resulting in coronary endothelial dysfunction. We hypothesized that chronic inhibition of PKC protects coronary endothelial function against DM and H/R injury. Methods: Genetically modified obesity and type-2 diabetic mice (female) were orally treated with or without selective PKCα/β inhibitor ruboxistaurin (10μg/g) for 4 weeks (n = 6/group). Coronary small arteries (70-110 μm in diameter) were then dissected from the harvested heart of mice. The isolated vessels were subjected to 60-min of hyperkalemic cardioplegic hypoxia (15°C) and then reperfused with oxygenated Krebs-Henseleit buffer for 60 minutes. At the end of 60-min re-oxygenation, all vessels was pretreated with endothelin-1 and then the responses to endothelium-dependent vasodilators, adenosine-diphosphate (ADP) and substance P were examined. Results: PKCα/β inhibition significantly improved the recovery of coronary endothelial function in the small coronary arteries of diabetic mice showing increased relaxation response to ADP and substance P in dose-dependent manner compared with the DM control (no-pretreatment alone) (*p<0.05). Conclusion: Chronic inhibition of PKC significantly improved the recovery of coronary endothelial function against a period of cardiolpegic H/R in the diabetic microvasculature. These data suggest that the PKC inhibitor ruboxistaurin represents a novel potential therapeutic for coronary endothelial dysfunctionin patients with DM following cardioplegic ischemia and reperfusion.

Prevalence of myocardial bridging associated with coronary endothelial dysfunction in patients with chest pain and non-obstructive coronary artery disease.

Myocardial bridging (MB), characterised by the epicardial coronary vessel diving into the myocardium, is present in up to one third of adults and is associated with angina and acute coronary syndromes. MB is accompanied by altered blood flow mechanics and regional changes in wall sheer stress. The purpose of this study was to determine the association between myocardial bridging and coronary endothelial dysfunction. Patients presenting with chest pain and found to have non-obstructive CAD (stenosis <40%) on angiography underwent an invasive assessment of epicardial and microvascular endothelial function. Epicardial endothelial function was assessed by measuring the percent change in coronary artery diameter in response to intracoronary infusions of acetylcholine (%ΔCADAch). Epicardial endothelial dysfunction was defined as a %ΔCADAch of <-20%. Microvascular endothelial function was assessed by the percent change in coronary blood flow in response to intracoronary infusions of acetylcholine (%ΔCBFAch), and microvascular endothelial dysfunction was defined as a %ΔCBFAch of <50%. MB was diagnosed angiographically by identifying the characteristic reduction in minimal luminal diameter during systole. Patients were divided into those with and those without MB, and the frequency of epicardial endothelial dysfunction and microvascular endothelial dysfunction was compared between patients with versus those without MB. Between 1993 and 2012, 1,469 patients (mean age 50.4 years, 35% male) underwent coronary angiography and invasive testing of endothelial function. Two hundred and eight (14.2%) patients were found to have MB in the LAD. Patients with any MB had a significantly higher frequency of endothelial dysfunction within the mid and/or distal vessel segment compared to patients without MB (60.1% vs 50.4%, p=0.012). In multivariate analyses, mid and/or distal vessel MB was a significant predictor of mid and/or distal vessel epicardial endothelial dysfunction (OR 1.44, 95% CI: 1.04-2.00, p=0.029) and of microvascular endothelial dysfunction (OR 1.34, 95% CI: 1.00-1.82, p=0.050). MB co-localises with epicardial endothelial dysfunction and is significantly associated with microvascular endothelial dysfunction in symptomatic patients with non-obstructive CAD, supporting its potential role as a mechanism for angina in symptomatic patients with MB.

Haptoglobin Phenotype Is Associated With High-Density Lipoprotein-Bound Hemoglobin Content and Coronary Endothelial Dysfunction in Patients With Mild Nonobstructive Coronary Artery Disease.

Objective- Coronary endothelial dysfunction (ED) is an early stage of atherosclerosis and is associated with impaired high-density lipoprotein (HDL) function. A functional polymorphism at the haptoglobin (Hp) gene locus (rs72294371) has been associated with marked differences in HDL structure and function. We sought to determine whether Hp phenotype was associated with coronary ED and whether the amount of hemoglobin (Hb) tethered to HDL via Hp was Hp-type dependent and associated with ED. Approach and Results- Microvascular and epicardial coronary endothelial function was assessed in 338 individuals with nonobstructive coronary artery disease. Microvascular ED was defined as <50% change in coronary blood flow and epicardial ED as ≥20% decrease in coronary artery diameter after intracoronary acetylcholine infusion. The amount of Hb bound to HDL was measured by ELISA after HDL purification from plasma samples using immune-affinity chromatography. One hundred and seventy of the individuals in this study (50.3%) were diagnosed with microvascular ED, 143 (42.3%) with epicardial ED, and 67 (19.7%) had diabetes mellitus (DM). Hp phenotype was significantly associated with microvascular ( P=0.01) and epicardial ED ( P=0.04) among DM individuals. There was a significant and inverse correlation between the amount of HDL-bound Hb and change in coronary blood flow (r=-0.40; P<0.0001) and in coronary artery diameter (r=-0.44; P<0.0001) in response to acetylcholine infusion. Hb content of HDL was significantly increased in individuals with Hp 2-2 and DM. In a logistic regression model, Hp 2-2 phenotype was associated with microvascular ED (odds ratio, 1.9; P=0.03) and the amount of HDL-bound Hb was an independent predictor of both microvascular (odds ratio, 4.6 for each 1-SD increase; P<0.0001) and epicardial (odds ratio, 2.2; P<0.0001) ED. Conclusions- Hp phenotype is significantly associated with coronary ED in DM individuals. This association is likely related to increased Hb tethering to HDL via Hp 2-2 in DM.

TCT-400 Prevalence of Myocardial Bridging Associated with Coronary Endothelial Dysfunction in Patients with Chest Pain and Non-Obstructive Coronary Artery Disease

TCT-400 Prevalence of Myocardial Bridging Associated with Coronary Endothelial Dysfunction in Patients with Chest Pain and Non-Obstructive Coronary Artery Disease

1344Myocardial bridging is associated with coronary endothelial dysfunction in patients with chest pain and non-obstructive coronary artery disease

1344Myocardial bridging is associated with coronary endothelial dysfunction in patients with chest pain and non-obstructive coronary artery disease

Late gadolinium enhancement on cardiac magnetic resonance imaging is associated with coronary endothelial dysfunction in patients with dilated cardiomyopathy.

Myocardial fibrosis and coronary endothelial dysfunction are important determinants of outcome in patients with heart failure. However, the relationship of these factors in patients with dilated cardiomyopathy (DCM) is not fully understood. This study aimed to investigate the relationship between endothelium-dependent coronary vasomotor abnormality and late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging (CMR) in patients with DCM. We examined 38 consecutive patients with DCM. All patients underwent CMR and the acetylcholine (ACh) provocation test using cardiac catheterization. During the ACh provocation test, we sampled blood simultaneously from the coronary sinus and aortic root to compare lactate concentrations, and quantified coronary blood flow volume using an intracoronary Doppler-tipped guidewire. LGE was detected in 17 (44.7%) patients. The lactate extraction ratio (LER) in the ACh provocation test was significantly decreased in the LGE-positive group (before vs after ACh, 18.6±13.6 vs -13.3±24.8%; p<0.001) and in the LGE-negative group (before vs after ACh, 14.2±19.5 vs 3.3±16.2%; p=0.02). The rate of patients with an LER<0% (indicating myocardial lactate production due to myocardial ischemia) was significantly higher in the LGE-positive group than in the LGE-negative group [12 (70.6%) vs 7 (33.3%); p=0.02]. Multivariable logistic regression analysis showed that a post-ACh LER<0% was a significant predictor of LGE positivity (odds ratio 7.75; 95% confidence interval 1.37-43.68; p=0.02). In conclusion, ACh-provoked coronary vasomotor abnormality is associated with myocardial fibrosis in patients with DCM. These results suggest that coronary endothelial dysfunction is involved in myocardial fibrosis and worsening heart failure concomitant with DCM.

Interleukin-1β is associated with coronary endothelial dysfunction in patients with mTOR-inhibitor-eluting stent implantation.

Implantation of mammalian target of rapamycin (mTOR)-inhibitor drug-eluting stents (DESs) impairs coronary endothelial function. There are no known non-invasive biomarkers of coronary endothelial dysfunction. We aimed to assess the association between serum interleukin-1beta (IL-1β) and coronary endothelial dysfunction in patients with mTOR-inhibitor DES implantation and to investigate the association between the mTOR pathway and IL-1β. We enrolled 35 patients who had implanted DESs for coronary artery disease. At a 10-month follow-up, peripheral venous blood samples were collected to measure IL-1β levels. Coronary endothelial dysfunction was evaluated by intracoronary infusion of incremental doses of acetylcholine. Serum IL-1β levels were significantly associated with the magnitude of vasoconstriction to acetylcholine at the segment distal (P < 0.05) but not proximal to the stent. Serum IL-1β levels were positively correlated with stent length (P < 0.05). To examine the direct effects of mTOR inhibition on IL-1β release, sirolimus was incubated in cultured human umbilical vein endothelial cells (HUVECs) or coronary artery smooth muscle cells (CASMCs). Sirolimus directly increased IL-1β mRNA expression (P < 0.01) and enhanced IL-1β release into the culture media (P < 0.01) in CASMCs, but not in HUVECs. Inhibition of mTOR triggers IL-1β release through transcriptional activation in CASMCs. Serum IL-1β levels are a potential biomarker for mTOR-inhibitor DES-associated coronary endothelial dysfunction.

Coronary endothelial function in patients with obstructive sleep apnea

Obstructive sleep apnea (OSA) has been associated with increased risk for cardiovascular events, possibly mediated by endothelial dysfunction. The current study evaluates the association between invasive coronary endothelial dysfunction and OSA in patients with nonobstructive coronary atherosclerosis. All patients who had undergone both polysomnography and an invasive coronary vasomotor study at the Mayo Clinic, Rochester, Minnesota, from January 1997 to August 2011 were identified (n=143). OSA was defined as an apnea-hypopnea index of 5 or higher. Three endpoints of coronary endothelial function - percentage change in coronary artery diameter at the mid and distal left anterior descending artery to intracoronary acetylcholine and percentage change in coronary blood flow to intracoronary acetylcholine - were assessed. Differences between patients with OSA (n=102) and those without OSA (n=41) were evaluated using multivariate analysis of variance. Follow-up mortality data were collected and Kaplan-Meier curves were plotted to evaluate differences in mortality between patients with and without OSA. Patients with OSA were more likely to have hypertension compared with patients without OSA. OSA was not significantly associated with coronary endothelial dysfunction on univariate analysis (P=0.23) and after adjustment for hypertension (P=0.19). Similarly, there was no significant difference in coronary endothelial function in patients who had oxygen desaturation of less than 90% during polysomnography (P=0.42). There was a trend toward higher mortality in patients with OSA compared with those without OSA, but this did not reach statistical significance (5 vs. 0% at 10 years, P=0.25). The current study suggests that OSA is not an independent risk factor for coronary endothelial dysfunction in patients with early coronary atherosclerosis. Adverse coronary outcomes in patients with OSA may be independent of coronary endothelial dysfunction.

Endothelial dysfunction in coronary heart disease is more than a systemic process

This editorial refers to ‘Coronary endothelial dysfunction in patients with early coronary artery disease is associated with the increase in intravascular lipid core plaque,[†][1]’ by B.-J. Choi et al. , on page 2047 Since its initial description by our laboratory, now 27 years ago, much has been learned about the causes and consequences of human endothelial dysfunction.1 Impairment of endothelial function assessed by nitric oxide bioavailability (referred to as endothelial dysfunction) has been observed in atherosclerosis,1 is associated with traditional risk factors,2,3 and has been described in the setting of various systemic inflammatory disorders linked to high rates of coronary heart disease.4 Endothelial dysfunction exerts a key role in precipitating myocardial ischaemia during daily activities.2,3 Endothelial dysfunction confers adverse cardiovascular prognosis independently of known risk factors and also by becoming a pathophysiological target for both known and unknown cardiovascular risk factors.2 Fortunately, endothelial function can be restored with treatments that also improve long-term outcomes.2,3 Notably, failure of treatments to re-establish normal endothelial function among individuals with coronary heart disease or in individuals with hypertension identifies a subset of individuals who remain at high risk for adverse clinical events.5 Thus, endothelial function testing may ultimately be used to identify the non-responders and to individualize treatment with the purpose of preventing future clinical events.5 The pharmaceutical industry has recognized the importance of endothelial function testing as a tool for development of antiatherosclerotic drugs as endothelial function can change rapidly in response to interventions.6 Lastly, ‘endothelial biopsies’ which allow for the isolation of human endothelial cells are enabling investigators to characterize the biology of the endothelium on a molecular level. During this procedure, endothelial cells are removed from blood vessels using guidewires and analysed, for example, for protein … [1]: #fn-2

Coronary endothelial dysfunction in patients with early coronary artery disease is associated with the increase in intravascular lipid core plaque†

Endothelial dysfunction is considered to play a key role in the development of atherosclerosis. However, only a limited number of human imaging studies have been available to demonstrate this hypothesis. The present study used near-infrared spectroscopy (NIRS) to investigate whether coronary endothelial dysfunction is associated with the lipid core plaque (LCP) in patients with early coronary artery disease. A total of 32 patients with chest pain who had diameter stenosis <30% were enrolled. All patients underwent coronary endothelial function assessment using intracoronary acetylcholine infusion and NIRS of the proximal left anterior descending artery. The lipid core burden index (LCBI), LCBI/L (LCBI divided by the length of scanned artery), maxLCBI4mm (maximum value of LCBI for any of the 4-mm segment) and block chemogram (yellow: probability of LCP presence >0.98, tan: 0.84 ≤ P ≤ 0.98, orange: 0.57 ≤ P ≤ 0.84, red: P < 0.57) were measured. The mean percentage of yellow, tan, and orange colour blocks in patients with epicardial endothelial dysfunction was significantly higher than in those with normal epicardial endothelial function (9.5 ± 11.4 vs. 3.1 ± 6.5%, P = 0.042). There was a significant correlation between LCBI (r = -0.460, P = 0.008), LCBI/L (r = -0.453, P = 0.009), and maxLCBI4mm (r = -0.431, P = 0.014) and the degree of epicardial endothelial function. However, there was no significant correlation between LCBI (r = -0.101, P = 0.58), LCBI/L (r = -0.099, P = 0.59), and maxLCBI4mm (r = -0.063, P = 0.73) and the degree of microvascular endothelial function. Patients with early coronary artery disease and endothelial dysfunction had a higher lipid content in the vascular wall than patients with normal endothelial function. The result of the present study supports the hypothesis that endothelial dysfunction is associated with pathogenesis of early atherosclerosis.

TCT-412: Impact of Age on Coronary Endothelial Dysfunction in patients with Myocardial Bridge

TCT-412: Impact of Age on Coronary Endothelial Dysfunction in patients with Myocardial Bridge

AS-190 Different Clinical Characteristics of Focal versus Diffuse Coronary Endothelial Dysfunction in Patients with Myocardial Bridge

Coronary endothelial dysfunction (CED) and subsequent clinical spasm at the myocardial bridge (MB) segment has been proposed as a risk factor for adverse cardiac events. There is limited data regarding clinical and angiographic characteristics according to CED extent/type whether focal or diffuse in patients (pts) with MB.

CYP4A11 polymorphism correlates with coronary endothelial dysfunction in patients with coronary artery disease—The ENCORE Trials

Background Cytochrome P450 (CYP) is expressed in the human endothelium and metabolizes arachidonic acid into vasoactive epoxyeicosatrienoic and 20-hydroxyeicosatetraenoic acids. CYP enzymes have been linked to hypertension and generation of reactive oxygen species. Thus, we investigated the impact of several CYP polymorphisms on coronary endothelial function in patients with coronary artery disease (CAD). Methods and results We determined CYP4A11 F434S, CYP2C9 I359L, CYP2C9 G144C and CYP 2J2 promotor -50G>T polymorphisms in 734 patients with CAD undergoing percutaneous coronary intervention. Increasing concentrations of acetylcholine were infused in a coronary segment without angiographically significant CAD and the coronary artery vasomotor response was measured by quantitative angiography. Patients with substitution of phenylalanine 434 by serine (434SS, n = 15, 2.04%) in CYP4A11 F434 demonstrated significantly augmented endothelium-dependent vasoconstriction ( p = 0.044 after Bonferroni correction) compared to patients with the 434FS ( n = 193, 26.29%) and 434FF genotype ( n = 526, 71.66%) before and after adjustment for blood pressure and HDL-cholesterol. In addition, patients with the 434SS genotype had higher systolic blood pressure levels ( p = 0.039) compared to the two other groups. The CYP 2C9 and CYP 2J2 polymorphisms did not show any correlation with coronary vasoconstriction, hypertension, diabetes mellitus, blood pressure or cholesterol. Conclusion In patients with established and stable coronary artery disease the 434SS variant of CYP4A11 F434 is associated with pronounced coronary vasoconstriction.

Segmental coronary endothelial dysfunction in patients with minimal atherosclerosis is associated with necrotic core plaques

Background/objective:Endothelial dysfunction and atherosclerosis are systemic disorders, but are often characterised by segmental involvement and complications. A potential mechanism for local involvement early in the disease process may be related...

A Prospective, Randomized, 6-Month Comparison of the Coronary Vasomotor Response Associated With a Zotarolimus- Versus a Sirolimus-Eluting Stent: Differential Recovery of Coronary Endothelial Dysfunction

We prospectively compared coronary endothelial dysfunction in patients with zotarolimus-eluting stent (ZES) versus sirolimus-eluting stent (SES) implantation at 6-month follow-up. A ZES has been associated with uniform and rapid healing of the endothelium. Fifty patients were randomly treated with intravascular ultrasound-guided stenting with a single stent to the mid-segment of the left anterior descending artery (20 ZES, 20 SES, and 10 bare-metal stents), and endothelial function was estimated before and after intervention at 6-month follow-up by incremental acetylcholine (Ach) (10, 20, 50, and 100 microg/min) and nitrate (200 microg/min) infusions into the left coronary ostium. The vascular response was quantitatively measured in the 5-mm segments proximal and distal to the stent. In the drug-eluting stent groups, more intense vasoconstriction to incremental doses of Ach was observed at 6-month follow-up compared with the responses before stenting. Endothelial function associated with the ZES was more preserved at 6-month follow-up compared with the SES. Vasoconstriction to Ach was more prominent in the distal segments than the proximal segments in both the ZES and SES groups. Endothelium-independent vasodilation to nitrate did not differ significantly among the study groups. Vasoconstriction in response to Ach in the peri-stent region was less pronounced in the ZES group than the SES group at 6-month follow-up, which suggests that endothelial function associated with ZES can be more preserved than the SES.

Coronary endothelial dysfunction associated with a depressive mood in patients with atypical angina but angiographically normal coronary artery

Background Depression is a risk factor for the development of coronary heart disease but the relationship between coronary endothelial dysfunction and depression is not yet known. This study investigated whether depressive symptomatology is associated with coronary endothelial dysfunction in patients without coronary artery disease (CAD). Methods and results Incremental acetylcholine (Ach; 20, 50 and 100 µg/min) and nitrate (200 µg/min) were infused into the left coronary ostium of 52 patients (male 30, 51.8 years) with depressive symptoms as indicated by a Beck Depression Inventory (BDI) score of ≥ 10 and a Hamilton Depression Rating Scale (HAM-D17) of ≥ 7 but without overt CAD or any vasoactive medications. Vascular responses to each drug were measured quantitatively at the mid-segments of the left anterior descending artery (LAD) and compared to those of 103 matched control subjects (male 64, 51.3 years) with angiographically normal looking LAD and as estimated by BDI < 10 and HAM-D17 < 7. Patients in the depressive group showed significant vasoconstriction compared with patients in the non-depressive group ( p = 0.017, 0.090, 0.004 respectively). However, endothelium-independent vasodilatation to nitrates did not differ significantly between the two groups ( p = 0.461). No differences in risk factors were found between the two groups. Conclusions Depressive mood is associated with coronary endothelial dysfunction in patients without CAD, suggesting a possible mechanism by which depressive mood may act as a cardiovascular risk factor.

Association Between the Paraoxonase-1 192Q>R Allelic Variant and Coronary Endothelial Dysfunction in Patients With Early Coronary Artery Disease

OBJECTIVE To test the hypothesis that allelic variants of the paraoxonase-1 gene are associated with endothelial dysfunction, an early stage of atherosclerosis. PATIENTS AND METHODS We assessed 192Q>R and 55L>M allelic variants of the paraoxonase gene and coronary endothelial function in response to intracoronary acetylcholine in 99 patients (52 with homozygous QQ, 47 with homozygous RR or heterozygous QR). The study was conducted from September 1, 2002, through November 30, 2004. RESULTS Of 52 homozygous QQ patients, 39 (75%) had endothelial dysfunction vs 20 (43%) of the 47 RR/QR patients (P=.001), and this association remained significant after adjustment in a multivariable linear regression model (P=.005). In homozygous QQ vs RR/QR patients, epicardial arterial diameter decreased more (percent change in diameter, -22%±21% vs -9%±16%, respectively, P=.002), coronary blood flow increased less (+37%±77% vs +75%±75%, P=.02) in response to acetylcholine, and oxidized LDL levels were higher. The 55L>M allelic variant was not significantly associated with endothelial dysfunction and had no effect on the association between endothelial dysfunction and the 192Q>R allelic variant. CONCLUSION The 192Q>R allelic variant of the paraoxonase-1 gene is associated with coronary endothelial dysfunction. The current study provides further information regarding the potential mechanisms by which this allelic variant contributes to early atherosclerosis in humans. To test the hypothesis that allelic variants of the paraoxonase-1 gene are associated with endothelial dysfunction, an early stage of atherosclerosis. We assessed 192Q>R and 55L>M allelic variants of the paraoxonase gene and coronary endothelial function in response to intracoronary acetylcholine in 99 patients (52 with homozygous QQ, 47 with homozygous RR or heterozygous QR). The study was conducted from September 1, 2002, through November 30, 2004. Of 52 homozygous QQ patients, 39 (75%) had endothelial dysfunction vs 20 (43%) of the 47 RR/QR patients (P=.001), and this association remained significant after adjustment in a multivariable linear regression model (P=.005). In homozygous QQ vs RR/QR patients, epicardial arterial diameter decreased more (percent change in diameter, -22%±21% vs -9%±16%, respectively, P=.002), coronary blood flow increased less (+37%±77% vs +75%±75%, P=.02) in response to acetylcholine, and oxidized LDL levels were higher. The 55L>M allelic variant was not significantly associated with endothelial dysfunction and had no effect on the association between endothelial dysfunction and the 192Q>R allelic variant. The 192Q>R allelic variant of the paraoxonase-1 gene is associated with coronary endothelial dysfunction. The current study provides further information regarding the potential mechanisms by which this allelic variant contributes to early atherosclerosis in humans.

Association Between the Paraoxonase-1 192Q&gt;R Allelic Variant and Coronary Endothelial Dysfunction in Patients With Early Coronary Artery Disease

To test the hypothesis that allelic variants of the paraoxonase-1 gene are associated with endothelial dysfunction, an early stage of atherosclerosis. We assessed 192Q>R and 55L>M allelic variants of the paraoxonase gene and coronary endothelial function in response to intracoronary acetylcholine in 99 patients (52 with homozygous QQ, 47 with homozygous RR or heterozygous QR). The study was conducted from September 1, 2002, through November 30, 2004. Of 52 homozygous QQ patients, 39 (75%) had endothelial dysfunction vs 20 (43%) of the 47 RR/QR patients (P=.001), and this association remained significant after adjustment in a multivariable linear regression model (P=.005). In homozygous QQ vs RR/QR patients, epicardial arterial diameter decreased more (% change in diameter, -22%+/-21% vs -9%+/-16%, respectively, P=.002), coronary blood flow increased less (+37%+/-77% vs +75%+/-75%, P=.02) in response to acetylcholine, and oxidized LDL levels were higher. The 55L>M allelic variant was not significantly associated with endothelial dysfunction and had no effect on the association between endothelial dysfunction and the 192Q>R allelic variant. The 192Q>R allelic variant of the paraoxonase-1 gene is associated with coronary endothelial dysfunction. The current study provides further information regarding the potential mechanisms by which this allelic variant contributes to early atherosclerosis in humans.