Salaheddin Akçay

Effects of normal blood pressure, prehypertension, and hypertension on autonomic nervous system function

BACKGROUND Autonomic nervous system plays an important role in blood pressure (BP) regulation, and large proportion of patients with hypertension have increased sympathetic and decreased parasympathetic activity. Heart rate recovery (HRR) is a simple non-invasive measurement for investigating autonomic nervous system influence on the cardiovascular system; however, this methodology has not been used to evaluate autonomic nervous system in subjects with prehypertension (PHT). Accordingly, the present study was designed to evaluate HRR in subjects with PHT. METHODS AND RESULTS We measured HRR of 91 subjects with PHT, 44 patients with hypertension, and 53 normotensive healthy volunteers. HRR was significantly lower in the HT and PHT groups as compared to the control group (24.4 ± 5.7, 26.0 ± 8.4, 30.0 ± 8.7; hypertension, PHT, and control groups, respectively), but it did not significantly differ between HT and PHT groups. HRR was significantly and inversely correlated with age, systolic and diastolic BP, fasting and postprandial glucose level, waist circumference, total cholesterol, LDL cholesterol and non-HDL cholesterol, whereas exercise duration and METs were positively correlated with HRR. In multivariable analysis, we found that systolic BP, postprandial glucose level and exercise duration were independent predictors of lower HRR. CONCLUSIONS HRR, a non-invasive measurement analyzing the dysfunction in autonomic nervous system, was reduced in subjects with PHT as compared to normotensives, and the subjects with PHT had HRR as lower as patients with HT did. Our findings are supportive for the hypothesis that autonomic dysregulation is present in an early stage of essential hypertension.

Effects of prediabetes and diabetes on left ventricular and coronary microvascular functions

BACKGROUND Coronary flow reserve (CFR) provides independent prognostic information in diabetic patients with known or suspected coronary artery disease. However, there have been no substantial data to evaluate CFR in prediabetics. Accordingly, we aimed to evaluate CFR in subjects with prediabetes using second harmonic transthoracic Doppler echocardiography. METHODS AND RESULTS We measured CFR of 65 subjects with prediabetes, 45 patients with overt type 2 diabetes, and 43 sex and age matched normoglycemic healthy subjects with normal glucose tolerance. Ages, gender, existence of hypertension or hypercholesterolemia, smoking status were similar among the groups. CFR was significantly lower in diabetics (2.15 ± 0.39) than in prediabetics (2.39 ± 0.45) and controls (2.75 ± 0.35); in addition, it was significantly lower in prediabetics than controls. Only 2 (5%) of control subjects had abnormal CFR (<2) but 11 (17%) prediabetic subjects and 19 (42%) diabetic patients had abnormal CFR. We found that only age (β=-0.31, P<0.01) and presence of the diabetes (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=-0.15, P=0.04), fasting glucose level (r=-0.27, P=0.001), postprandial glucose level (r=0.43, P<0.001), hemoglobin A1C level (r=-0.34, P<0.001), LDL cholesterol level (r=0.22, P=0.009), mitral A velocity (r=-0.27, P=0.001) and Tei index (r=-0.19, P=0.02), whereas mitral E/A ratio, mitral Em (r=0.18, P=0.02), mitral Em/Am ratio (r=0.23, P=0.004) were significantly and positively correlated with CFR. CONCLUSION CFR is impaired in subjects with prediabetics, but this impairment is not as severe as that in diabetics.

Relationships of Different Blood Pressure Categories to Indices of Inflammation and Platelet Activity in Sustained Hypertensive Patients with Uncontrolled Office Blood Pressure

Failure to decrease blood pressure (BP) normally during nighttime (non-dipping) in hypertension is associated with higher cardiovascular morbidity and mortality. In addition, non-dipping BP is associated with increased platelet activity and inflammatory response; however, there has been no study to evaluate the relationship of non-dipping BP to indices of platelet activity and inflammation in uncontrolled hypertensive patients. In the present study, hypertensive subjects with uncontrolled office BP were firstly divided into three groups: 84 subjects with white coat effect and 365 subjects with true uncontrolled hypertension. Then, true uncontrolled hypertensive patients were divided into two groups: 158 patients with dipping and 207 patients with non-dipping. Mean platelet volume (MPV), uric acid (UA), γ-glutamyltransferase (GGT), C-reactive protein (CRP), and high-sensitivity CRP (hs-CRP) levels were studied. The general characteristics and risk factors for coronary artery disease (CAD) of the study population were similar among the groups. MPV, UA, GGT, CRP, and hs-CRP levels were significantly higher in non-dipper group than both dipper and white coat effect groups, and were significantly higher in dipper group than in white coat effect group (MPV: 9.1 ± 1.3, 8.7 ± 1.1, and 8.0 ± 0.9 fL; UA: 6.9 ± 1.2, 5.9 ± 1.4, and 4.1 ± 0.8 mg/dL; GGT: 38.9 ± 11.1, 33.6 ± 14.9, and 25.2 ± 9.2 U/L; CRP: 7.1 ± 2.4, 6.2 ± 1.9, and 3.9 ± 0.8 mg/dL; hs-CRP: 3.8 ± 1.5, 3.3 ± 1.2, and 2.0 ± 0.6, non-dipper, dipper, and white coat effect groups, respectively, all p values <0.01). All study parameters strongly correlated with each other. In conclusion, in hypertensive patients with uncontrolled office BP, presence of non-dipping BP is associated with increased platelet activity and inflammation, which can be one of the underlying plausible mechanisms of non-dipping BP status.

The effects of good glycaemic control on left ventricular and coronary endothelial functions in patients with poorly controlled Type 2 diabetes mellitus

Diabetics are at risk for developing overt heart failure and subclinical left ventricular (LV) dysfunction. Also, impaired coronary flow reserve (CFR) reflecting coronary microvascular dysfunction is common in diabetics. However, no substantial data regarding the effects of good glycaemic control on subclinical LV dysfunction and CFR are available.

Echocardiographic predictors of progression from prehypertension to hypertension.

Background: Prehypertension (PHT) was recently introduced by replacing former categories of high–normal and above-optimal blood pressure (BP). The rationale for redefining this new category was to emphasize the excess cardiovascular risk associated with BP in this range and to focus high risk for developing hypertension (HT). However, no clear definite markers to identify prehypertensive patients at high risk of progressing to HT have been established yet. Accordingly, we aimed to establish echocardiographic predictors of progression from PHT to HT. Methods and results: The study population consisted of 98 eligible prehypertensive patients. All patients underwent echocardiographic examination including coronary flow reserve (CFR) at baseline. Twenty-nine (30%) patients developed HT during the 3-year follow-up period. Creatinine level, left ventricular mass index (LVMI), mitral Em and Em/Am had a trend towards a significant crude odds ratio (OR) for the development of HT; however, only baseline SBP [OR = 1.18, 95% confidence interval (CI)  = 1.06–1.31; P = 0.002), having metabolic syndrome (OR = 3.75, 95% CI = 1.43–9.78; P = 0.007), high-density lipoprotein (HDL) cholesterol (OR = 0.92, 95% CI = 0.86–0.98; P = 0.01), presence of microalbuminuria (OR = 3.53, 95% CI = 1.11–11.2; P = 0.03) and CFR (OR = 0.65, 95% CI = 0.53–0.77; P = 0.02) were significant independent predictors of progression of PHT into HT. The best cutoff value of CFR to predict incident HT was 1.98 with 94% sensitivity and 79% specificity. Conclusion: This prospective study suggested that baseline SBP, having metabolic syndrome, HDL cholesterol level, presence of microalbuminuria and CFR reflecting coronary microvascular function, but not left ventricular diastolic function parameters, were significant independent markers to identify participants with PHT at high risk for incident HT.

The effect of fixed-dose combination of valsartan and amlodipine on nighttime blood pressure in patients with non-dipper hypertension

OBJECTIVE Failure to decrease blood pressure (BP) during the night is associated with higher cardiovascular (CV) morbidity and mortality. There is strong evidence that fixed-dose combinations (FDCs) of antihypertensive agents are associated with significant improvement and non-significant adverse effects. The aim of the present study was to evaluate whether FDC affected nocturnal BP favorably in patients with uncontrolled, non-dipper hypertension (HT). METHODS All non-dipper hypertensives were either newly diagnosed with stage 2-3 HT or had HT uncontrolled with monotherapy. Patients (n=195) were consecutively assigned to 4 treatment groups: FDC of valsartan/amlodipine (160/5 mg), free-drug combination of valsartan 160 mg and amlodipine 5 mg, amlodipine 10 mg, and valsartan 320 mg. Ambulatory blood pressure monitoring (ABPM) was repeated at 4th and 8th week. RESULTS Average 24-h (24-hour) and nocturnal BP were similar among the groups at baseline evaluation, and had significantly decreased by the fourth week of treatment. However, BP continued to decrease only slightly between the 4th and 8th weeks in the valsartan and amlodipine monotherapy groups, but continued to decrease significantly in both combination groups. After 4 weeks, day-night BP difference and day-night BP % change were significantly elevated in the combination and valsartan groups. Between the 4th and 8th weeks, however, day-night BP difference and day-night BP % change continued to rise only in the FDC group, nearly reducing to baseline levels in the free-drug combination and valsartan groups. An additional 2.2 mmHg decrease was observed in the FDC group, compared to the free-drug combination group. CONCLUSION In non-dipper HT, FDC of valsartan and amlodipine improved diurnal-nocturnal ratio of BP and provided 24-h coverage.

Evaluation of coronary sinus strain in patients with dipper and nondipper hypertension.

ObjectiveHypertension has been reported to affect both the left and the right ventricular functions, but its effect on the coronary sinus has not been investigated. The aim of this study was to investigate the effect of systemic hypertension on the cardiac venous system by evaluating the coronary sinus strain (CSS). MethodsOne-hundred and twelve hypertensive patients without diabetes and 44 healthy individuals (the control group) were evaluated consecutively at the outpatient clinic and enrolled in the study. CSS was evaluated by echocardiography in all the participants before blood pressure evaluations. Twenty-four-hour ambulatory blood pressure monitoring enabled the study population to be divided into two groups: 52 patients with dipper pattern hypertension and 60 with nondipper pattern hypertension. ResultsNondipper pattern patients had significantly lower values of CSS compared with the participants in the control group (140.8±54.2 and 193.9±48.1, P<0.001). Similarly, dipper pattern patients had significantly lower values of CSS values compared with the controls (164±68.4 and 193.9±48.1, P=0.036). On comparing the three groups, the CSS values showed a progressive decrease from normal individuals to dipper and nondipper hypertension patients. Correlation analysis indicated a positive correlation between the aortic strain and the CSS (r=0.247, P=0.002). There was a weak correlation between left ventricular mass and CSS (r=−164, P=0.041). ConclusionOur study suggests that systemic hypertension may affect the cardiac venous system as well as the arterial system, which has been reported in many papers. The effect on the venous system may be more pronounced in nondipper pattern hypertension.

The Relationship between Endothelial Nitric Oxide Synthase Gene Polymorphism (G894T) and Isole Coronary Artery Ectasia

Atilla _ Içli, Ahmet Altınbaş, Yasin Türker, Habil Yücel, Salaheddin Akçay, Recep Sütçü, Fatih Aksoy, Akif Arslan, Şenol Tayyar, Bayram Ali Uysal Department of Cardiology, Ahi Evran University Education and Research Hospital, Kırsehir, Department of Cardiology, Suleyman Demirel University, Isparta, Department of Cardiology, Duzce University, Düzce, Department of Cardiology, Isparta State Hospital, Isparta, Department of Cardiology, Celal Bayar University, Manisa, Department of Biochemistry, Katip Celebi University, _ Izmir

Beta Fibrinogen -455 G>A Gene Polymorphism in Coronary Artery Ectasia

Aim: Atherosclerosis is an inflammatory arterial wall disease and T lymphocytes have important role in the pathogenesis and progression of this disease. The aim of this study is determination of vitamin A supplementation effects on gene expression of cytokines secreted by TCD4+ lymphocytes in atherosclerotic patients. Methods-Materials: Thirty one atherosclerotic patients and 12 healthy controls participated in this study. Patients were randomly divided into vitamin A receiving group (n1⁄416) and placebo receiving group (n1⁄415), also healthy controls were receiving vitamin A. vitamin A supplement was given as retinyl palmitate and 25000 IU per day. Fasting blood sample of participants were taken before and after 4 months and plasma was separated and stored at -80 0C for biochemical laboratory tests. Peripheral blood mononuclear cells (PBMC) were separated and cultured in the appropriate number along with PHA and ox-LDL for proliferation assay and determination of gene expression pattern. As well as RNA was extracted and cDNA was synthesized from part of the cells at the same time and was stored for Real-Time PCR analysis. After 72 hour incubation cells supernatant were collected and stored at-800C; cells deposited were collected for PNA extraction and cDNA synthesis. After the intervention period the gene expression pattern of relevant cytokines of CD4+ T cells including Th1, Th2, Th17 and Treg were determined by Real-Time PCR. Results: There was significant difference in fasting blood sugar, total cholesterol and LDL cholesterol between three groups of study, before and after intervention. Vitamin A increased proliferation of cells that stimulated with ox-LDL in all groups. Results of this study show that IFN-y and Tbet gene expression in fresh cells in vitamin Atreated patients was decreased. The IL-4 gene expression was increased 12.7 fold in vitamin A-treated patients. IL-17 gene expression in fresh cells of vitamin A-treated patients was diminished. Foxp3 gene expression in fresh cells was increased after intervention in all groups. Conclusion: vitamin A supplementation had no significant effect on anthropometric factors and effect of this intervention on biochemical factors limited to increase in total cholesterol and HDL cholesterol in both groups of patients and controls but the amounts were in normal value ranges. Vitamin A supplementation could reduce gene expression of IFN-y T-bet in all patients. Increase in gene expression of Th2 cells was seen in all group expect GATA3 gene. According to the results of how the effect of vitamin A on gene expression in atherosclerotic patients, perhaps we thought the positive role of vitamin A supplementation in these patients. Results of this study could pave the way for a more detailed review on effect of vitamin A in patients with immune related diseases.

Plasma lipoprotein(a) levels in patients with slow coronary flow.

Introduction Slow coronary flow (SCF) is a microvascular disorder characterized by delayed opacification of coronary vessels with normal coronary angiogram. It may be due to endothelial dysfunction and diffuse atherosclerosis. Lipoprotein(a) [Lp(a)] is related to cardiovascular events. Plasma Lp(a) levels have not been studied previously in SCF patients. Aim We investigated plasma Lp(a) and fibrinogen levels, and their relation to coronary flow rate in patients with SCF. Material and methods This cross-sectional study included 50 patients with SCF and 30 age- and sex-matched controls who had normal coronary arteries and normal flow. Coronary flow rates of patients and controls were counted with the thrombolysis in myocardial infarction (TIMI) frame count. Plasma Lp(a) and fibrinogen levels were measured in SCF patients and controls, with routine biochemical tests. Results There were no significant differences between the two groups with respect to plasma Lp(a) (21 mg/dl vs. 14 mg/dl, p = 0.11) and fibrinogen (278 mg/dl vs. 291 mg/dl, p = 0.48) levels. The TIMI frame count was not correlated with plasma Lp(a) (r = 0.13, p = 0.25) or fibrinogen (r = –0.14, p = 0.28) levels. Conclusions Our results show that there is no significant association between SCF and Lp(a) and fibrinogen levels.