Ozgur Ciftci

Effects of Normal Blood Pressure, Prehypertension, and Hypertension on Coronary Microvascular Function

Background— The assessment of coronary flow reserve (CFR) by transthoracic Doppler echocardiography has recently been introduced into clinical practice, and reduced CFR has been suggested to be a sensitive indicator of hypertensive end-organ damage; however, to date, this methodology has not been used to evaluate CFR in subjects with prehypertension. Accordingly, the present study was designed to evaluate CFR in subjects with prehypertension. Methods and Results— We measured CFR of 40 subjects with prehypertension, 60 patients with hypertension, and 50 normotensive healthy volunteers using transthoracic Doppler echocardiography. None of the subjects had any systemic disease. Age, gender, body mass index, heart rate, lipid profiles, fasting glucose levels, and hemoglobin were similar among the 3 groups. CFR was significantly lower in the hypertension group than in the prehypertension and control groups; in addition, it was significantly lower in subjects with prehypertension than in control subjects (2.23±0.47, 2.54±0.48, and 2.91±0.53, respectively). Furthermore, we found that prehypertension (β=−0.31, P<0.01) and hypertension (β=−0.57, P<0.01) were significant predictors of lower CFR in a multivariable model that adjusted for other variables. CFR was significantly and inversely correlated with age (r=−0.20, P=0.01), systolic blood pressure (r=−0.51, P<0.01), diastolic blood pressure (r=−0.47, P<0.01), high-sensitivity C-reactive protein levels (r=−0.21, P=0.01), left atrium diameter (r=−0.22, P<0.01), mitral E deceleration time (r=−0.19, P=0.02), and mitral A velocity (r=−0.27, P<0.01), whereas mitral E/A ratio was significantly and positively correlated with CFR (r=0.26, P<0.01). Conclusions— CFR is impaired in subjects with prehypertension, but this impairment is not as severe as that in hypertension.

Impaired Coronary Flow Reserve in Hemodialysis Patients: A Transthoracic Doppler Echocardiographic Study

Background: Coronary flow reserve (CFR) reflects the functional capacity of microcirculation to adapt to blood demand during increased cardiac work. In this study, CFR of hemodialysis patients with angiographically normal coronary arteries was evaluated using transthoracic second harmonic Doppler echocardiography. Methods and Results: Ten hemodialysis patients, and 14 sex-, age- and left ventricular mass index-matched hypertensive controls with angiographically normal coronary arteries underwent transthoracic second harmonic Doppler echocardiographic examination. Coronary basal diastolic peak flow velocities and hyperemic peak flow velocities after dipyridamole infusion (0.56 mg/kg over 4 min) were measured. CFR was defined as the ratio of hyperemic to basal diastolic peak velocities. CFR ≧2.0 was regarded as normal. Additionally, Doppler tissue imaging pulse wave measurements were taken from the lateral and septal corners of the mitral annulus. CFR values were significantly lower in the study group than in the control group (2.03 ± 0.3 vs. 2.61 ± 0.5, p = 0.005). In 5 of 10 hemodialysis patients, CFR was <2.0 (50%), however in only 1 of 14 control patients it was <2.0 (5%). Conclusions: Impairment of coronary microvasculature occurs earlier in patients with chronic renal failure and may be the harbinger of subsequent primary uremic myocardial disease. In patients with chronic renal failure and normal coronary arteries, decreased CFR by transthoracic echocardiography might be regarded as an early finding of an affected coronary vasculature.

Impaired coronary microvascular function and increased intima-media thickness in rheumatoid arthritis

BACKGROUND Rheumatoid arthritis (RA) is associated with excessive cardiovascular mortality. Recently, some studies have shown endothelial dysfunction in RA patients with high inflammatory activity. In addition, it has been suggested that the chronic inflammatory state of RA contributes to accelerated atherosclerosis. Therefore, we aimed to evaluate whether coronary microvascular dysfunction and increased carotid artery intima-media thickness exist in patients with a long history and well controlled disease activity of RA lacking traditional cardiovascular risk factors. METHODS Thirty RA patients (22 women; mean age 43.7+/-9.0) and 52 healthy volunteers (38 women; mean age 45.3+/-5.4) were included into the study. Using transthoracic echocardiography, each subject underwent echocardiographic examination including coronary flow reserve (CFR) and carotid intima-media thickness (IMT) measurement. RESULTS CFR values were statistically reduced for RA patients as compared to controls (2.4+/-0.5 vs. 2.7+/-0.4, P=0.002) whereas IMT values were significantly increased (0.6+/-0.1 vs. 0.5+/-0.1, P=0.001). In RA patients, CFR positively correlated with lateral Em/Am ratio (r=0.399, P=0.029), and negatively correlated with lateral isovolumic relaxation time (IVRT) (r=-0.744, P=0.005), IMT (r=-0.542, P=0.002) and RA disease duration (r=-0.495, P=0.005). Reflecting LV diastolic function, mitral E-wave deceleration time and isovolumic relaxation time were borderline significant between the groups, however lateral Em/Am ratio and lateral IVRT were statistically different. CONCLUSIONS Patients with RA had impaired CFR and increased carotid IMT, and these injurious effects correlated significantly with disease duration.

Nebivolol Improves Coronary Flow Reserve in Patients with Idiopathic Dilated Cardiomyopathy

Background: Impaired coronary flow reserve (CFR) is a significant predictor of poor prognosis in patients with idiopathic dilated cardiomyopathy (IDC). Nebivolol reduces mortality and morbidity in patients with heart failure and left ventricular dysfunction, including cases caused by IDC. Objective: To assess the effects of nebivolol on CFR in patients with IDC. Methods: CFR was measured in 21 clinically stable patients with IDC (mean (SD) ejection fraction 35.7 (6.2)) at baseline and after 1 month of treatment with nebivolol once daily. A control group of apparently healthy subjects who were matched for age and sex was used for comparison. Resting and hyperaemic coronary flows were measured using transthoracic second-harmonic Doppler echocardiography. None of the subjects had any systemic disease. Results: After 1 month of treatment, heart rate was reduced significantly (p<0.001). The blood pressure was decreased significantly (p<0.001). The left ventricular end-diastolic diameter and stroke volume were not changed significantly, but end-systolic diameter was decreased significantly (p<0.05). Resting rate–pressure product was lower after treatment with nebivolol, but dipyridamole-induced change was not influenced by the treatment. Nebivolol treatment reduced significantly coronary velocities at rest (p<0.02) and also caused a significant increase in coronary velocities after dipyridamole (p<0.02), leading to a greater CFR (2.02 (0.35) vs 2.61 (0.43), p<0.001). Nebivolol induced an absolute increase of 6% in the CFR in 17 of 21 patients (80.9%). Conclusions: In patients with IDC, 1 month of treatment with nebivolol induces a marked increase in CFR.

Effects of normal blood pressure, prehypertension and hypertension on left ventricular diastolic function and aortic elastic properties

Background. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (BP) provides guideline for the new category of BP levels as normal, prehypertension (PHT), and hypertension. Although PHT is associated with a markedly increased risk of developing hypertension within 4 years, its prognostic significance and predisposition to target‐organ damage is unknown. Accordingly, we evaluated the effects of normal BP, PHT and hypertension on left ventricular (LV) diastolic function and aortic elasticity, which are sensitive indicators of target‐organ damage. Methods. We evaluated LV diastolic function and aortic elastic properties of 60 subjects with PHT, 70 patients with hypertension and 50 normotensive healthy volunteers using transthoracic echocardiography. None of the subjects had any systemic disease. Results. LV diastolic function was more significantly impaired in the hypertension group than in the PHT group compared with controls, but it was not strongly different between the PHT and control group. Aortic distensibility was significantly lower, and aortic stiffness index was significantly higher in both the hypertension and the PHT group than those in the control group. However, aortic elastic properties did not significantly differ between the PHT and hypertension groups. Furthermore, we found that the presence of the PHT was significant predictor of impaired aortic elasticity in a multivariable model that adjusted for other variables. Conclusions. Aortic elastic properties are significantly and LV diastolic function is slightly impaired in subjects with PHT, and impairment of aortic elasticity is as severe as that in hypertension.

The influence of circadian blood pressure changes on aortic distensibility and left ventricular diastolic function in hypertensive individuals

Background: Failure to decrease blood pressure (BP) normally during nighttime, which is called non-dipper, in hypertensive individuals is associated with higher cardiovascular morbidity and mortality. In addition, non-dipper BP leads to structural changes in the left ventricle; however, the influences of non-dipper BP on aortic elastic properties and left ventricular diastolic function have not been studied yet. Methods: In this study, we evaluated aortic elastic properties and left ventricular diastolic function of 22 subjects with non-dipper hypertension, and 15 subjects with dipper hypertension using transthoracic second harmonic standard and tissue Doppler echocardiography (Acuson Sequoia C256®). None of the subjects had any systemic disease or coronary risk factor except hypertension. Results: Age, gender, body mass index, lipids, and standard echocardiographic findings including left ventricular mass index were similar between the groups. Office BP recordings were similar between non-dipper and dipper groups (147.9±6.1/93.9±4.3 vs. 144.0±8.0/93.0±3.7). Daytime and 24-h ambulatory BP measurements were similar within the groups, but nighttime BPs were significantly greater in non-dipper group than those were in dipper group. Left ventricular diastolic parameters obtained by both standard and tissue Doppler did not differ between the non-dipper and dipper groups. However, aortic distensibility was found to be slightly lower (4.1±2.4 vs. 4.9±1.9, p=0.08), and aortic stiffness index (6.3±0.5 vs. 6.1±0.4, p=0.08) and elastic modulus (6.2±2.5 vs. 4.8±2.3, p=0.08; groups non-dipper and dipper respectively) higher in non-dipper group than in dipper group. However, these differences were not statistically significant. Conclusion: Left ventricular remodeling and diastolic function were similar in patients with non-dipper and dipper hypertension. However, aortic elastic properties were slightly impaired in non-dipper hypertensives than those were in dipper ones, but these differences did not reach statistically significance.

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 owing to the lower nicotine and tar yield. Objective: To compare the chronic and acute effects of light cigarette and regular cigarette smoking on coronary flow velocity reserve (CFVR). Methods: 20 regular cigarette smokers (mean (SD) age 24.8 (5.0)), 20 light cigarette smokers (mean age 25.6 (6.4)), and 22 non-smoker healthy volunteers (mean age 25.1 (4.2)) were included. First, each subject underwent echocardiographic examination, including CFVR measurement, after a 12 hour fasting and smokeless period. Two days later, each subject smoked two of their normal cigarettes in a closed room within 15 minutes. Finally, within 20–30 minutes, each subject underwent an echocardiographic examination, including CFVR measurement. Results: Mean (SD) CFVR values were similar in light cigarette and regular cigarette smokers and significantly lower than in the controls (2.68 (0.50), 2.65 (0.61), 3.11 (0.53), p = 0.013). Before and after smoking a paired t test showed that smoking two light cigarettes acutely decreased the CFVR from 2.68 (0.50) to 2.05 (0.43) (p = 0.001), and smoking of two regular cigarettes acutely decreased CFVR from 2.65 (0.61) to 2.18 (0.48) (p = 0.001). Conclusion: Smoking low-tar, low-nicotine cigarettes impairs the CFVR as severely as smoking regular cigarettes. CFVR values are similar in light cigarette and regular cigarette smokers and significantly lower than in controls.

Impaired coronary microvascular and left ventricular diastolic function in patients with inflammatory bowel disease.

BACKGROUND AND AIM Increased incidence of coronary vascular events in patients with inflammatory bowel disease (IBD) is known. However, the association between coronary microvascular function and IBD has not been fully defined. We aimed to investigate whether coronary flow reserve (CFR) and left ventricular diastolic function were impaired in IBD patients. METHODS Seventy-two patients with IBD (36 patients with ulcerative colitis [UC] and 36 Crohns disease [CD]) were registered. Each subject was evaluated after a minimum 15-day attack-free period. For the control group, 36 age- and sex-matched healthy volunteers were included into the study. IBD clinical disease activity in UC was assessed by the Truelove-Witts Index (TWAS) and in CD by the Crohns Disease Activity Index (CDAI). In each subject, CFR was measured through transthoracic Doppler echocardiography. RESULTS Compared to the controls, the CD group and UC group had significantly higher high-sensitivity C-reactive protein (hs-CRP) and erythrocyte sedimentation rate. Baseline diastolic peak flow velocity (DPFV) of the left anterior descending artery (LAD) was significantly higher in the IBD group (24.1±3.9 vs. 22. 4±2.9, p<0.05), and hyperemic DPFV (56.1±12.5 vs. 70.6±15.3, p<0.05) and CFR (2.34±0.44 vs. 3.14±0.54, p<0.05) were significantly lower in the IBD group than in the control group. In stepwise linear regression analysis, hs-CRP and lateral Em/Am ratio were independently correlated with CFR. CONCLUSION CFR, reflecting coronary microvascular function, is impaired in patients with IBD. CFR and left ventricular diastolic function parameters are well correlated with hs-CRP.

Increased morning blood pressure surge and coronary microvascular dysfunction in patient with early stage hypertension

Morning blood pressure surge (MBPS) is defined as an excessive increase in blood pressure (BP) in the morning from the lowest systolic BP during sleep, and it has been reported as a risk factor for cardiovascular events in current clinical studies. In this study, we evaluated the association between the rate of BP variation derived from ambulatory BP monitoring data analysis and coronary microvascular function in patients with early stage hypertension. One hundred seventy patients with prehypertension and Stage 1 hypertension who fulfilled the inclusion and exclusion criteria were included in the study. We divided our study population into two subgroups according to the median value of coronary flow reserve (CFR). Patients with CFR values <2.5 were defined as the impaired CFR group, and patients with CFR values ≥2.5 were defined as the preserved CFR group, and we compared the MBPS measurements of these two subgroups. CFR was measured using transthoracic Doppler echocardiography (TTDE). Ambulatory 24-hour systolic and diastolic BP, uric acid, systolic MBPS amplitude, diastolic MBPS amplitude, high-sensitivity C-reactive protein, and mitral flow E/A ratio were statistically significant. These predictors were included in age- and gender-adjusted multivariate analysis; ambulatory 24-hour systolic BP (ß = 0.077, P < .001; odds ratio [OR] = 1.080; 95% confidence interval [CI] [1.037-1.124]) and systolic MBPS amplitude (ß = 0.043, P = .022; OR = 1.044; 95% CI [1.006-1.084]) were determined to be independent predictors of impaired CFR (Hosmer-Lemeshow test, P = .165, Nagelkerkes R(2) = 0.320). We found that increased changes in MBPS values in patients with prehypertension and Stage 1 hypertension seemed to cause microvascular dysfunction in the absence of obstructive coronary artery disease.

Patients with Behcet's disease carry a higher risk for microvascular involvement in active disease period

Background. Behcets disease (BD) is characterized with remissions and exacerbations. However, to date, there is no study to investigate a possible association of disease activity (active versus inactive disease period) with cardiovascular complications. Methods. Forty patients with BD were evaluated in both active and in inactive disease period. For the control group 45 healthy volunteers, age and sex matched, were registered. Subjects with at least a 15‐day lesion‐free period were regarded in inactive disease period, and subjects with any oral, skin, and/or genital lesion was regarded as in active disease period. In each subject coronary diastolic peak flow velocities (DPFV) were measured at baseline and after dipyridamole infusion (0.84 mg/kg over 6 minutes) using an Acuson Sequoia C256® echocardiography system. Coronary flow reserve (CFR) was defined as the ratio of hyperemic to baseline DPFV. Results. CFR values were significantly lower in BD patients compared to the controls (2.57±0.50 versus 2.87±0.53, P = 0.006). In active disease period, basal DPFV (24.6±7.5 versus 27.3±6.6, P = 0.019) was significantly higher than in the inactive disease period. In the active disease period hyperemic DPFV (61.7±14.9 versus 56.8±16.7, P = 0.015) values decreased significantly. Therefore, in the active disease period CFR significantly decreased from 2.57±0.50 to 2.09±0.46, P<0.001. The only independent predictor of CFR within the active disease period was the disease duration (β = −0.384, P = 0.012). Conclusion. Within the active disease period, coronary microvascular function is more prominently impaired in BD patients. Therefore, BD patients are possibly more vulnerable to cardiovascular manifestations when they are in an active disease period.