Coronary Microvascular Functions Research Articles

Association Between Global Sleep Quality and Coronary Microvascular Function in Male Physicians With Occupational Burnout.

Occupational burnout has been associated with an increased risk of coronary heart disease, although the mechanisms involved are elusive. We investigated whether poor global sleep quality is associated with impaired coronary microvascular function in male physicians, a professional group at increased risk of burnout. Study participants were 30 male physicians with clinical burnout and 30 controls without burnout defined by the Maslach Burnout Inventory. Global sleep quality was measured with the Pittsburgh Sleep Quality Index (PSQI). Endothelium-dependent (cold pressor test) and endothelium-independent (adenosine challenge) coronary microvascular functions were quantified with myocardial perfusion positron emission tomography. In multivariable analyses, the interaction between burnout and the PSQI global score was regressed on measures of coronary microvascular function, adjusting for age, body mass index, physical activity, alcohol consumption, and main effects of burnout and PSQI score. The prevalence of poor sleepers (PSQI score >5) was 40% in the burnout group and 10% in the control group. Adjusting for covariates, burnout-by-global PSQI score interactions were observed for myocardial blood flow (MBF) at rest ( r partial = -0.30, p = .025), endothelium-dependent coronary flow reserve ( r partial = -0.26, p = .062), MBF response ( r partial = -0.30, p = .028), and hyperemic MBF ( r partial = -0.34, p = .012). The global PSQI score was inversely associated with these MBF measures in the burnout group relative to the control group. No significant interactions emerged for endothelium-independent MBF. In male physicians with occupational burnout, poor global sleep quality was associated with reduced endothelium-dependent coronary microvascular function, suggesting a mechanism by which burnout may affect cardiovascular health.

Predominance of Heart Failure With Preserved Ejection Fraction in Postmenopausal Women: Intra- and Extra-Cardiomyocyte Maladaptive Alterations Scaffolded by Estrogen Deficiency.

Heart failure (HF) remains a public health concern as it is associated with high morbidity and death rates. In particular, heart failure with preserved ejection fraction (HFpEF) represents the dominant (>50%) form of HF and mostly occurring among postmenopausal women. Hence, the initiation and progression of the left ventricular diastolic dysfunctions (LVDD) (a typically clinical manifestation of HFpEF) in postmenopausal women have been attributed to estrogen deficiency and the loss of its residue cardioprotective effects. In this review, from a pathophysiological and immunological standpoint, we discuss the probable multiple pathomechanisms resulting in HFpEF, which are facilitated by estrogen deficiency. The initial discussions recap estrogen and estrogen receptors (ERs) and β-adrenergic receptors (βARs) signaling under physiological/pathological states to facilitate cardiac function/dysfunction, respectively. By reconciling these prior discussions, attempts were made to explain how the loss of estrogen facilitates the disruptions both ERs and βARs-mediated signaling responsible for; the modulation of intra-cardiomyocyte calcium homeostasis, maintenance of cardiomyocyte cytoskeletal and extracellular matrix, the adaptive regulation of coronary microvascular endothelial functions and myocardial inflammatory responses. By scaffolding the disruption of these crucial intra- and extra-cardiomyocyte physiological functions, estrogen deficiency has been demonstrated to cause LVDD and increase the incidence of HFpEF in postmenopausal women. Finally, updates on the advancements in treatment interventions for the prevention of HFpEF were highlighted.

The Influence of On-pump Versus Off-pump Surgery on Short- and Medium-term Postoperative Coronary Flow Reserve After Coronary Artery Bypass Grafting.

Although several clinical trials have compared surgical outcomes between off-pump and on-pump coronary artery bypass grafting (CABG), whether there is a difference in the early- and medium-term postoperative coronary microvascular functions is not fully understood. We compared short- and medium-term coronary microvascular function after off-pump and on-pump CABG. A prospective study of patients undergoing off-pump and on-pump CABG. Eighty-two patients scheduled for CABG were recruited: 38 underwent off-pump surgery and 44 on-pump surgery. Each participant's coronary flow reserve (CFR) and diastolic function were measured with transthoracic Doppler echocardiography six and 12 months after surgery. Baseline and hyperaemic diastolic peak flow velocity in the left anterior descending artery were similar in both groups, as was CFR (2.22±0.66) in the off-pump group compared with (2.13±0.61) in the on-pump group, (P=0.54). Coronary flow reserve was significantly and inversely correlated with high sensitivity C-reactive protein concentration (r=-0.416; P<0.001) and positively correlated with mitral E/A-wave velocity ratio (r=0.247; P=0.02). Stepwise linear regression analysis revealed that only high sensitivity C-reactive protein concentration was independently correlated with CFR (β=-0.272, P=0.02). Heart-lung bypass technique had no medium-term influence on the coronary microcirculation, despite a possible initial unfavourable effect. Serum hs-CRP concentration was an independent predictor of medium-term coronary microvascular dysfunction.

Peripheral Arterial Function and Coronary Microvascular Function in Patients with Variant Angina

Objectives: In this study, we assessed whether any abnormalities in coronary microvascular and peripheral vasodilator functions are present in patients with variant angina (VA) caused by epicardial coronary artery spasm (CAS). Methods: We studied 23 patients with VA (i.e. angina at rest, ST-segment elevation during angina attacks and documented occlusive CAS at angiography) and 18 matched healthy controls. Endothelium-dependent and -independent coronary microvascular function was assessed by measuring coronary blood flow (CBF) response to adenosine and the cold pressor test (CPT) in the left anterior descending artery by transthoracic Doppler echocardiography. Systemic endothelium-dependent and -independent arterial dilator function was assessed by measuring brachial flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD), respectively. Results: In VA patients, CBF responses to both adenosine (1.71 ± 0.25 vs. 2.97 ± 0.80, p < 0.01) and CPT (1.68 ± 0.23 vs. 2.58 ± 0.60, p < 0.01) were reduced compared to controls. Brachial FMD was also lower (3.87 ± 2.06 vs. 8.51 ± 2.95%, p < 0.01), but NMD was higher (16.7 ± 1.8 vs. 11.9 ± 1.4%, p < 0.01) in patients compared to controls. Differences were independent of the presence of coronary atherosclerotic lesions at angiography. Conclusions: Our data show that patients with VA have a generalized vascular dysfunction that involves both peripheral artery vessels and coronary microcirculation.

Effects of Paclitaxel and Carboplatin combination on mechanical myocardial and microvascular functions: a transthoracic Doppler echocardiography and two-dimensional strain imaging study.

Paclitaxel and carboplatin are frequently used chemotherapy drugs in the treatment of gynecologic malignancies. Little is known about their effects on left ventricular mechanical and coronary microvascular functions. Thirty consecutive patients were prospectively enrolled. Patients underwent transthoracic echocardiography (TTE) before and after chemotherapy, to evaluate left ventricular mechanical functions and coronary flow reserve (CFR). A comprehensive TTE, tissue Doppler and two-dimensional (2D) strain imaging were performed and coronary flow velocity was measured at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities. Mitral annular velocities by tissue Doppler, peak strain, and systolic strain rate by velocity vector imaging (VVI) were measured. Baseline measurements were compared with healthy controls (n = 26). No patient developed heart failure (HF) symptoms, no significant change occurred in left ventricular ejection fraction or cardiac output and no significant difference was observed in CFR after chemotherapy. Baseline mean longitudinal peak strain and systolic stain rate were similar between patients and controls: -17.5 ± 2.6% versus -17.6 ± 2.2% (P = NS) and -1.04 ± 0.14/sec versus -1.05 ± 0.12/sec (P = NS). Peak strain and systolic strain rate decreased significantly after chemotherapy (from -17.5 ± 2.6% to -16.2 ± 2.5%, P < 0.02; and from -1.05 ± 0.12/sec to -0.96 ± 0.11/sec, P = 0.01, respectively). However, mean longitudinal velocity did not change significantly. Paclitaxel and carboplatin combination did not impair CFR; however, this chemotherapy combination could induce subtle impairment in myocardial mechanical function which can be detected by advanced deformation imaging techniques rather than by tissue Doppler imaging or conventional 2D and Doppler echocardiography.

Endothelial regulation of coronary microcirculation in health and cardiometabolic diseases

Cardiometabolic disorders have been shown to impair coronary microvascular functions leading to diminished cardiac performance and increased mortality. In this review, we focus on the molecular pathomechanisms of impaired endothelium-dependent and flow-induced dysregulation of coronary vasomotor tone in cardiometabolic disorders such as obesity, diabetes mellitus or hyperhomocysteinemia based on animal experiments and human studies. We also briefly summarize the relationship among key signaling mechanisms that contribute to the development of coronary dysfunctions in these disorders, which may help develop new targets for efficient cardiometabolic prevention and treatments.

Evaluation of coronary microvascular function in patients with vasospastic angina

To investigate endothelium-dependent and -independent coronary microvascular functions in patients with vasospastic angina (VSA). Thirty-six patients with VSA (30 men and 6 women; mean age, 58 years) were enrolled in this study. VSA was defined as ≥ 90% narrowing of the epicardial coronary arteries on angiography performed during a spasm provocation test, presence of chest pain, and/or ST-segment deviation on an electrocardiogram (ECG). Patients (n = 36) with negative spasm provocation test results and those matched for age and sex were enrolled as a control group (nonVSA group). Low-dose acetylcholine (ACh; 3 μg/min) was infused into the left coronary ostium for 2 min during the spasm provocation test. Following the spasm provocation test, nitroglycerin (0.2 mg) was administered intracoronally. Coronary blood flow (was calculated from quantitative angiography and Doppler flow velocity measurements, and the coronary flow reserve was calculated as the ratio of coronary flow velocity after injection of adenosine triphosphate (20 μg) to the baseline value. Changes in the coronary artery diameter in response to ACh and nitroglycerin infusion were expressed as percentage changes from baseline measurements. Body mass index was significantly lower in the VSA group than in the nonVSA group. The frequency of conventional coronary risk factors and the rate of statin use were similar between the 2 groups. The left ventricular ejection fraction as evaluated by echocardiography was similar between the 2 groups. The duration of angina was 9 ± 2 mo. The results of blood chemistry analysis were similar between the 2 groups. Low-dose ACh did not cause coronary spasms. The change in coronary artery diameter in response to ACh was lower in the VSA group (-1.4% ± 9.3%) than in the nonVSA group (3.1% ± 6.5%, P < 0.05), whereas nitroglycerin-induced coronary artery dilatation and coronary blood flow increase in response to ACh or coronary flow reserve did not differ significantly between the 2 groups. These findings suggest that microvascular coronary function may be preserved despite endothelial dysfunction of the epicardial coronary arteries in patients with VSA.

Measurement of the coronary flow velocity reserve in patients with non-alcoholic fatty liver disease

Endothelial dysfunction is an early and reversible feature in the pathogenesis of atherosclerosis. Coronary flow velocity reserve is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. This study was designed to evaluate the carotid intima-media thickness and myocardial microvascular circulation in patients with non-alcoholic fatty liver disease. Twenty-four patients with non-alcoholic fatty liver disease and 28 healthy subjects were studied. According to the pathology of liver biopsies, patients with non-alcoholic fatty liver disease were divided into non-alcoholic fatty liver and nonalcoholic steatohepatitis groups. Coronary diastolic peak flow velocities were measured at baseline, and then dipyridamole infusion was measured by transthoracic Doppler echocardiography. The ratio of hyperemic to baseline diastolic peak velocities was calculated and the intima-media thicknesss of the carotid arteries were measured. Baseline average diastolic peak and diastolic mean flow velocities were similar between non-alcoholic fatty liver disease patients and healthy subjects. However, hyperemic average diastolic peak and diastolic mean flow velocities were significantly lower in the patient groups compared to those in the controls (p=0.005 and p=0.002). Coronary flow velocity reserve was 1.65 ± 0.36 and 2.67 ± 0.81 in patients and healthy subjects, respectively (p < 0.001). The intima-media thickness was similar between the patients with non-alcoholic fatty liver disease and healthy subjects. The comparison of patients with non-alcoholic fatty liver and non-alcoholic steatohepatitis within the non-alcoholic fatty liver disease group with respect to coronary flow velocity reserve and intima-media thickness yielded no statistical differences. The present study showed that coronary flow velocity reserve, which establishes coronary microvascular and endothelial functions noninvasively, is significantly impaired in patients with non-alcoholic fatty liver disease. The impaired coronary flow velocity reserve-like early atherosclerotic changes may have value in the prediction of coronary artery disease in patients with non-alcoholic fatty liver disease.

Association between Serum Total Antioxidant Status and Coronary Microvascular Functions in Patients with SLE

Mortality from cardiovascular disease has been found to be increased in patients with systemic lupus erythematosus (SLE). Coronary flow reserve (CFR) measurement is used both to assess epicardial coronary arteries and to examine the integrity of coronary microvascular circulation. Oxidative stress, enhancing modification of plasma lipids, is also associated with atherosclerotic events in lupus patients. Impairment of CFR and TAS has been shown to be an early manifestation of coronary atherosclerosis. Forty patients with SLE and 33 healthy volunteers were included in this study. Echocardiographic examination included left ventricular myocardial velocity measurements and coronary flow reserve (CFR) measurement. Serum total antioxidant status levels (TAS) also were measured using TAS kit. Lateral myocardial early peak velocity (Em) and lateral Em/Am ratio did not differ between the groups, but lateral myocardial atrial peak velocity (Am) was significantly higher in SLE group than the control group. Baseline coronary diastolic peak flow velocity (DPFV) of left anterior descending was similar in both the groups. However, hyperemic DPFV and CFR (2.50 ± 0.42 vs. 3.09 ± 0.45, P < 0.0001) were significantly lower in the SLE group than in the control group. CFR significantly and inversely correlated with CRP and significantly correlated with TAS. Subclinical coronary microvascular dysfunction can occur in SLE patients without traditional cardiovascular risk factors, probably associated with underlying inflammation and impairment of TAS.

Plasma Ghrelin Levels Are Associated with Coronary Microvascular and Endothelial Dysfunction in Peritoneal Dialysis Patients

Cardiovascular (CV) disease is the main cause of death in peritoneal dialysis (PD) patients, and endothelial dysfunction (ED) is an early sign of vascular pathology. Ghrelin, a gastric peptide with CV actions, has been shown to inhibit proatherogenic changes in experimental models. However, another peptide hormone, leptin, may mediate deleterious effects on the CV system. The aim of this study is to evaluate the relationship between plasma ghrelin and leptin levels, and their association with coronary microvascular and endothelial functions in PD patients. Twenty-four (14 females and 10 males; mean age 44 ± 12 yr) nondiabetic PD patients, between 18 and 70 years of age, were enrolled. In addition to demographic, clinical, and laboratory parameters, plasma concentrations of ghrelin and leptin were evaluated. Endothelial functions of the coronary arteries were determined by coronary flow reserve (CFR) measurement using transthoracic Doppler echocardiography (TTDE). A CFR value of < 2 was used as an evidence for ED. When the study group was divided according to CFR measurements as CFR < 2 and ≥ 2, there were no significant differences considering age, gender, etiology of renal disease, body mass index (BMI), duration of dialysis, PD modality, PD solution type, history of peritonitis, mean arterial pressure, ejection fraction, and biochemical parameters between the two subgroups. Plasma ghrelin levels (129.4 ± 82.1 pg/mL) in patients with CFR ≥ 2 were significantly higher than those in patients with CFR< 2 (63.3 ± 35.8 pg/mL) (p = 0.03). However, no significant differences in plasma leptin levels were found between these groups [31.39 ± 37.81 ng/mL vs. 63.95 ± 72.83 ng/mL (p = 0.28)]. No correlation existed between plasma ghrelin levels and age, BMI, duration of dialysis, mean arterial pressure, ejection fraction, plasma leptin levels, and biochemical parameters. Decreased plasma ghrelin levels may contribute to the development of atherosclerosis in PD patients by causing ED.

Acute Effects of Smoking Light Cigarettes on Coronary Microvascular Functions

To date, there has been no study comparing the possible acute effects on coronary microvascular functions of smoking light cigarettes (those with low tar and nicotine yield) and regular cigarettes. Twenty healthy volunteers (8 women and 12 men; mean age, 25.8 +/- 5.8 years) were included in a single-blind, open-label, cross-over study to compare the effects of smoking light cigarettes (containing 0.6 mg nicotine, 8 mg tar, 9 mg carbon monoxide) and smoking regular cigarettes (containing 0.9 mg nicotine, 12 mg tar, 12 mg carbon monoxide) on coronary flow reserve (CFR). For each participant, CFR values were measured at baseline, after smoking 2 regular or light cigarettes, and 15 days later after smoking 2 cigarettes of the other kind. After smoking 2 cigarettes, CFR values declined from 2.8 +/- 0.56 (baseline) to 2.31 +/- 0.51 after smoking light cigarettes (P = .003), and from 2.8 +/- 0.56 (baseline) to 2.21 +/- 0.45 after smoking regular cigarettes (P < .001). After smoking light and regular cigarettes, CFR values were similar (P = .678). Light cigarette smoking has similar acute detrimental effects on coronary microvascular function and CFR as does regular cigarette smoking.

Coronary flow reserve dysfunction in hemodialysis and kidney transplant patients

The assessment of coronary flow reserve (CFR) by trans-thoracic echocardiography has recently been introduced into clinical studies. Impairment of coronary microvascular functions and decreased CFR detected by trans-thoracic Doppler harmonic echocardiography (TTDE) has recently been reported in hemodialysis (HD) patients, but there is no comparative study between HD patients and renal transplant recipients. The aim of our study was to evaluate coronary microvascular circulation in chronic HD patients and renal transplant recipients. Forty-eight chronic HD patients, 27 renal transplant patients and 39 normotensive healthy controls were studied for the assessment of CFR by TTDE. The carotid artery intima media thickness (IMT) and areas of focal plaque formation were also evaluated in all subjects. CFR values were significantly lower in both the HD and renal transplant groups than in the control group (p = 0.00). CFR values (1.57 +/- 0.32 vs. 1.89 +/- 0.50, p = 0.01) were also significantly lower in the HD group than in the renal transplant group. In 43 of 48 (89.6%) HD patients, CFR was <2.0; however, in 16 of 27 (59.3%) renal transplant recipients it was <2.0 (p = 0.00). When the HD and renal transplant groups were divided into two subgroups, according to CFR measurements (CFR < 2 and > or =2), no significant differences were found with respect to coronary risk factors and left ventricular echocardiographic measurements. The IMT of the control group (0.586 +/- 0.163 mm) was significantly lower than the HD (0.799 +/- 0.218 mm) and renal transplant groups (0.681 +/- 0.148 mm; p = 0.00). The IMT of the HD patients (0.799 +/- 0.218 mm) was significantly higher than the renal transplant recipients (0.681 +/- 0.148 mm; p = 0.01). Renal transplant and HD patients had lower CFR values detected by TTDE, which may be regarded as an early finding of an affected cardiovascular system. CFR is more impaired in HD patients than renal transplant recipients. Uremia-associated microvascular disease may be responsible for CFR impairment in HD patients.

Smoking mentholated cigarettes impairs coronary microvascular function as severely as does smoking regular cigarettes

Objective — Smoking mentholated cigarettes inhibits the metabolism of nicotine and increases systemic exposure to cigarette smoke toxins. However, the possible effects of smoking mentholated cigarettes on coronary microvascular functions are unknown.We sought to investigate whether smoking mentholated cigarettes impairs coronary flow reserve (CFR) more so than smoking regular cigarettes.Methods — Twenty otherwise healthy smokers of regular cigarettes (6 women, 14 men; mean age, 25.6 ± 6.4 years) and 22 non-smoking control subjects were included in the study.To compare the acute effects of mentholated (0.9 mg nicotine, 11 mg tar, 12 mg carbon monoxide) and regular (0.9 mg nicotine, 12 mg tar, 12 mg carbon monoxide) cigarettes on CFR, all subjects underwent an echocardiographic examination that included CFR measurements at baseline. Twenty to 30 minutes after subjects had smoked 2 regular cigarettes and 2 mentholated cigarettes, CFR was again measured in subjects in the smoking group.Results — In response to smoking 2 regular and 2 mentholated cigarettes, CFR values declined from 2.56 ± 0.60 to 2.06 ± 0.38 (P < 0.004) and from 2.56 ± 0.60 to 2.14 ± 0.30 (P < 0.005), respectively. Smoking mentholated and regular cigarettes impaired CFR to the same degree (P =0.547).Conclusions — When compared with smoking regular cigarettes, smoking mentholated cigarettes has similar acute detrimental effects on coronary microvascular functions.

Light cigarette smoking impairs coronary microvascular functions as severely as smoking regular cigarettes

Background:Smoking is the most prevalent and most preventable risk factor for cardiovascular diseases. Smoking low-tar, low-nicotine cigarettes (light cigarettes) would be expected to be less hazardous than smoking regular cigarettes...

Cardiovascular prognostic value of vascular involvement in Behcet's disease

We measured carotid artery intima-media thickness (IMT), brachial artery flow mediated dilation (FMD), and coronary flow reserve (CFR) in 38 Behcet’s disease (BD) patients without vascular involvement, 15 BD patients with vascular involvement, and 35 control subjects. BD patients with and without vascular involvement were similar regarding carotid IMT (0.52 ± 0.14; 0.51 ± 0.09; 0.46 ± 0.09; P = 0.051), and brachial FMD (16.3 ± 6.8; 16.5 ± 9.1). CFR values were significantly impaired in BD patients compared to the controls; however the BD patients with and without vascular involvement were similar regarding CFR (2.66 ± 0.45; 2.62 ± 0.48; 2.91 ± 0.53, P = 0.007 with and without vascular involvement and the controls, respectively). Endothelial and coronary microvascular functions are compromised in BD patients without vascular involvement as remarkably as that in patients with vascular involvement.

Coronary flow reserve is impaired in patients with adult growth hormone (GH) deficiency

Relationship between adult growth hormone deficiency (AGHD) and increased cardiovascular disease risk is very well known in hypopituitary patients treated with conventional hormone replacement therapy other than growth hormone (GH) administration. Endothelial dysfunction, an early and reversible event in pathogenesis of atherosclerosis, is associated with increased vascular smooth muscle tone, arterial stiffening and intima-media thickness (IMT). Coronary flow reserve (CFR) measurement by transthoracic Doppler echocardiography (TTDE) reflects coronary microvascular and endothelial functions, as a cheaper and an easy screening test. We have used TTDE to evaluate endothelial function and coronary microvascular function in AGHD. Cross-sectional observational study. A total of 10 GH-deficient adults on conventional replacement therapy other than GH (4 males, 6 females; mean age 37 +/- 11 years) and 15 healthy subjects (7 males, 8 females; mean age 41 +/- 11 years) were studied. Patients and controls were all nonsmokers, normotensive and nondiabetic. IGF-1, free T4, lipid profile, insulin, glucose, insulin resistance (IR), anthropometrical and physical parameters were recorded. CFR recordings and IMT measurements were performed using the Vivid 7 echocardiography device. IMT were significantly higher in patients than controls (0.70 + 0.19 mm and 0.53 + 0.13 mm, respectively; P = 0.02). CFR was significantly lower in patients than in controls (1.96 +/- 0.35 and 2.62 +/- 0.45, respectively; P < 0.001). CFR was positively correlated with IGF-1 levels (r = 0.54, P = 0.005). CFR is significantly lower in adults with GH deficiency than in controls. Direct correlation between CFR and IGF-1 concentrations suggests GH replacement could improve microvascular function and thereby could decrease cardiovascular morbidity and mortality in AGHD.

Metformin therapy improves coronary microvascular function in patients with polycystic ovary syndrome and insulin resistance

Women with polycystic ovary syndrome (PCOS) are thought to have increased cardiovascular risk. Metformin therapy reduces whole-body insulin resistance (IR) in patients with type-2 diabetes mellitus (DM). As insulin resistance accompanying PCOS may be reversed by metformin therapy, we hypothesized that metformin therapy might improve coronary microvascular functions in women with PCOS and IR. We treated 16 women with PCOS and IR with metformin, and measured coronary flow reserve (CFR) at the beginning and after 6 months of metformin therapy using transthoracic second-harmonic Doppler echocardiography. At the end of the 6 months of metformin therapy, baseline coronary diastolic peak flow velocity (DPFV) did not change significantly (from 24.6 +/- 4.3 to 23.0 +/- 3.1, P = 0.106); however, hyperaemic coronary DPFV (from 68.2 +/- 12.7 to 74.5 +/- 9.7, P = 0.08), and CFR (from 2.75 +/- 0.48 to 3.3 +/- 0.5, P = 0.016) was significantly improved by metformin therapy. In women with PCOS, coronary microvascular function and CFR are significantly improved by 6 months of therapy with metformin.

Coronary flow reserve and coronary microvascular functions are strongly related to serum uric acid concentrations in healthy adults

Uric acid is a well known antioxidant; however, the relationship between serum uric acid levels and oxidative stress-caused disorders including cardiovascular diseases is not clear yet. Transthoracic Doppler echocardiographic measurement of coronary flow reserve is a useful tool to investigate coronary flow reserve and coronary microvascular functions. In this study, we investigated the possible association between serum uric acid concentrations and coronary flow reserve in healthy adults. One hundred healthy volunteers with normal uric acid levels, between 18 and 55 years of age, were included in this study. The study group was divided into two with regard to the serum uric acid levels. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion (0.56 mg/kg over 4 min) using echocardiography. Coronary flow reserve and hyperemic mean peak flow velocity were significantly greater in participants with lower serum uric acid concentrations (< or =234 micromol/l for women, < or =302 micromol/l for men) than in those with higher serum uric acid concentrations (>234 micromol/l for women, >302 micromol/l for men) (2.91+/-0.5 vs. 2.47+/-0.5, P<0.001; 66.8+/-11.4 vs. 61.1+/-16.5, P=0.04). The baseline mean peak flow velocity was significantly greater in participants with higher serum uric acid concentrations than in those with lower serum uric acid concentrations (24.7+/-4.1 vs. 23.1+/-2.4, P=0.02). Lower serum uric acid concentrations might be regarded as indicative of coronary microvascular and conductance vessel functionality.

High Serum Bilirubin Concentrations Preserve Coronary Flow Reserve and Coronary Microvascular Functions

Elevated serum bilirubin concentrations protect against atherosclerotic diseases; however, it is not clear whether higher serum bilirubin concentrations in physiological ranges work in favor of the cardiovascular system in younger persons with no cardiovascular risk factors. Accordingly, we investigated the effects of high, intermediate, and low serum bilirubin concentrations on coronary flow reserve (CFR). Fifty-two healthy subjects with hyperbilirubinemia (total bilirubin 1.43+/-0.33 mg/dL; mean age 35.9+/-7.3), 55 subjects with intermediate bilirubin level (total bilirubin: 0.69+/-0.11 mg/dL; mean age: 36.4+/-6.8), and 53 healthy subjects with hypobilirubinemia (total bilirubin 0.37+/-0.08 mg/dL; mean age, 37.6+/-6.6) were studied. Transthoracic second harmonic Doppler echocardiography examination was performed using an Acuson Sequoia C256 Echocardiography System. Coronary diastolic peak flow velocities were measured at baseline and after dipyridamole infusion (0.84 mg/kg over 6 minutes). CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocities. Demographic features, coronary risk factors, echocardiographic measurements, and biochemical measurements were similar among the 3 groups, except high-sensitivity C-reactive protein (hsCRP). CFR values were significantly higher in subjects with high bilirubin concentrations than those were in the intermediate and the low bilirubin groups (3.19+/-0.73; 2.75+/-0.42; 2.56+/-0.52, respectively; P<0.0001), and hsCRP levels were significantly lower in subjects with high bilirubin concentrations than those in both intermediate and low bilirubin groups (1.4+/-1.0, 2.0+/-1.7, 3.0+/-1.9 mg/L, respectively; P<0.001). hsCRP levels correlated with total bilirubin concentration and with CFR. Elevated serum bilirubin concentrations protect from CFR impairment, coronary microvascular dysfunction, and possibly coronary atherosclerosis.