Endothelial Dysfunction Markers in Low Cardiovascular Risk Individuals: Comparison of Males and Females.

BACKGROUND: Cardiovascular diseases (CVD) account for approximately 50% of the total deaths in Turkey. Most of them are related with atherosclerotic coronary heart disease. Predictive value of endothelial dysfunction markers related with the earliest stage of atherosclerosis has been getting more attention. We hypothesized that differences in endothelial dysfunction biochemical markers among genders would aid to capture proatherogenic activity that was not diagnosed by conventional risk assessment scoring systems. METHODS: We assessed the endothelial dysfuntion markers in 92 Turkish adults who were in the ¼low CV risk group« according to ESC (European Society of Cardiology)-Score Risk Charts. We compared the males and females. RESULTS: We observed higher endothelial dysfunction rates in males, with higher median and mean levels of e-NOS, ox-LDL before and after adjustment for HDL lowness and obesity (P=0.018, P=0.036 for NOS; P=0.000, P=0.004 for ox-LDL, respectively). Men had higher hs-CRP levels than females before adjustment (P=0.021). Decreased e-NOS levels were related with FMD for females before adjustment for confounders (P=0.028). We also found significant correlation between e-NOS and ox-LDL levels both before (r=0.360, P<0.001) and after adjustment (r=0.366, P<0.01) for confounders which pointed out the nitrosative stress. In multivariate regression analyses, after adjusting for other endothelial dysfunction markers which were not included in the ESC-risk scoring system, decreased e-NOS levels were independently asssociated with impaired flow mediated dilatation for females (odds ratio 0.3; P=0.038). CONCLUSIONS: Our results underline the importance of gender in evaluating endothelial dysfunction biochemical markers to assess cardiovascular risk for low CV risk indivuals.

Relation of Biochemical Parameters with Flow-mediated Dilatation in Patients with Metabolic Syndrome.

BACKGROUND: Metabolic syndrome (MetS) is one of the high cardiovascular (CV) situations. Endothelial dysfunction, which is a common finding in patients with MetS, is related with increased CV risk. In patients with MetS, the effect of the major CV risk factors, not included in the MetS definition, on endothelial dysfunction is not well known. The aim of this study was to determine the effect of major CV risk factors such as gender, smoking, family history, and biochemical parameters on endothelial dysfunction in patients with MetS. METHODS: The study was performed between December 2010 and August 2014. A total of 55 patients (15 females and 40 males) with MetS and 81 healthy controls (37 females and 44 males) with a body mass index <25 kg/m2 were enrolled in the study. Endothelial dysfunction was measured by flow-mediated dilatation (FMD), oxidative stress parameters; high-sensitivity C-reactive protein (hs-CRP), oxidized low-density lipoprotein (ox-LDL), endothelial nitric oxide synthase (e-NOS), nitric oxide, and cell adhesion markers; von Willebrand factor, and e-selectin. Platelet aggregation (endothelial adenosine diphosphate), total platelet count, and mean platelet volume were additionally analyzed and demographic parameters were explored. Student's t- test, Mann-Whitney U-test, and Chi-square test were used to analyze the results. RESULTS: The fasting blood glucose (z= 3.52, P= 0.001), hs-CRP (z = 3.23, P= 0.004), ox-LDL (z = 2.62, P= 0.013), and e-NOS (z = 2.22, P= 0.026) levels and cardiac risk score (z = 5.23, P< 0.001) were significantly higher in patients with MetS compared with the control group. Smoking was correlated with decreased FMD (χ2 = 9.26, P= 0.002) in MetS patients but not in the control group. CONCLUSIONS: Increased ox-LDL, hs-CRP, and e-NOS are likely to be a result of oxidative stress, a condition in which an imbalance occurs between the production and inactivation of reactive nitrogen and oxygen species. In addition, in patients with MetS, smoking is independently related to endothelial dysfunction.

Efficacy and safety of valsartan/amlodipine single-pill combination in patients with essential hypertension (PEAK LOW).

OBJECTIVES: This study evaluated the efficacy as well as the safety and tolerability profile of low-dose valsartan/amlodipine (Val/Amlo) single-pill combination (SPC) (160/5 mg) in patients with essential hypertension in Turkey. STUDY DESIGN: Adult patients with essential hypertension [systolic blood pressure (SBP)>140 mmHg and/or diastolic blood pressure (DBP)>90 mmHg], who were on low dose Val/Amlo (160/5 mg) SPC before enrollment and gave informed consent, were accepted for this multi-centric observational study performed at 30 sites. The absolute changes in SBP and DBP from baseline were the primary efficacy outcomes. Safety assessments consisted of recording all adverse events. RESULTS: Of 381 patients enrolled, 327 completed the study; 39% were females. The mean age was 57.3±11.8 years. Median duration of hypertension was 38 months. Both SBP and DBP values showed reductions from 162.6±16.6 mmHg and 94.0±13.2 mmHg to 137.6±14.2 mmHg and 81.9±9.0 mmHg at 4th week and to 131.6±11.5 mmHg and 79.7±7.6 mmHg at 12th week, respectively. The control and response rates at the end of the study were 82.0% and 92.6%, respectively. Twelve patients (3.2%) experienced a total of 12 adverse events; there were no serious adverse events. The most common adverse event was edema (1.3%). Patient compliance was approximately 99%. CONCLUSION: Low-dose (160/5 mg) Val/Amlo SPC is efficacous and has a good tolerability and safety profile for the management of essential hypertension in Turkey.

The association of MDR1 C3435T and G2677T/A polymorphisms with plasma platelet-activating factor levels and coronary artery disease risk in Turkish population.

Increased levels of peripheral proinflammatory mediators can contribute to the development of coronary artery disease (CAD). Platelet activating factor (PAF) is an important proinflammatory mediator and plasma levels of PAF correlate with transmembrane transporter multidrug resistant 1 P-glycoprotein (MDR1 Pgp) expression and activity. MDR1 polymorphisms can affect the expression and activity of Pgp and plasma PAF levels. Therefore, we investigated the possible relationship between MDR1 C3435T and G2677T/A polymorphisms and plasma PAF levels and the risk of CAD. The study population consisted of 198 patients angiographically documented CAD, including 113 cases with at least 1 coronary artery with ≥50% luminal diameter stenosis and 85 control subjects with strictly normal coronary angiograms. Genotypes of the MDR1 C3435T and G2677T/A polymorphisms were determined by polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP). Plasma PAF levels were detected by enzyme-linked immunosorbent assay (ELISA). There were no significant differences among plasma PAF levels in regard to MDR1 C3435T and G2677T polymorphisms in CAD patients and controls. No statistically significant difference was found for the genotypic and allelic distributions of the polymorphisms in the MDR1 gene between the patients and the control subjects. Furthermore, analysis of MDR1 haplotypes did not show any associations with increased plasma PAF levels and risk of CAD. Our results suggest that plasma PAF levels are not associated with MDR1 gene polymorphisms. There is no association between MDR1 C3435T and G2677T/A polymorphisms and the risk of CAD in Turkish patients.

Effect on quality of life of different accelerated diagnostic protocols for management of patients presenting to the emergency department with acute chest pain.

This study assessed the effects on quality of life (QoL) of dobutamine-atropine stress echocardiography (DASE) and electrocardiogram exercise testing (EET) accelerated diagnostic protocols for early stratification of low-risk patients with acute chest pain (ACP). A total of 290 patients with ACP, a nondiagnostic electrocardiogram, and negative biomarkers were randomly assigned to an accelerated diagnostic protocol (DASE, n = 110, or EET, n = 89) or usual care (n = 91) and followed up for 2 months. QoL was assessed at discharge and 2-month follow-up using the Nottingham Health Profile questionnaire. Baseline and 2-month follow-up answers to the Nottingham Health Profile questionnaire were available for 207 patients (71%; 55 in the usual-care, 77 in the DASE, and 75 in the ETT arm). At predischarge, patients in the usual-care arm reported higher impairment in the physical mobility and pain dimensions compared with the DASE and EET arms (p = 0.019 and p = 0.023, respectively). At 2-month follow-up, QoL improved in all groups; however, patients in the usual-care arm had significantly worse scores than patients managed using accelerated diagnostic protocols in the physical mobility, pain, social isolation, emotional reactions, and energy level dimensions (p = 0.014, p = 0.002, p = 0.04, p = 0.01, and p = 0.003, respectively). In conclusion, low-risk patients with ACP had non-negligible impairment of QoL in the acute phase. Emergency department ADPs with early DASE and EET reduced QoL impairment at both baseline and 2-month follow-up.

Impact of dyslipidemia on cardiovascular risk stratification of hypertensive patients and association of lipid profile with other cardiovascular risk factors: results from the ICEBERG study.

BACKGROUND: Hypertension, dyslipidemia, and other cardiovascular risk factors are linked epidemiologically, clinically, and metabolically. Intensive/Initial Cardiovascular Examination regarding Blood Pressure levels, Evaluation of Risk Groups (ICEBERG) study focuses on the effect of dyslipidemia on cardiovascular risk evaluation and association of lipid profile with other risk factors. PATIENTS AND METHODS: The ICEBERG study consisted of two sub-protocols: ICEBERG-1, conducted at 20 university hospitals (Referral Group) and ICEBERG-2, conducted at 197 primary healthcare centers (Primary Care Group). Sub-protocol had two patient profiles: patients previously diagnosed with essential hypertension and under medical treatment (Treated Group) and patients with systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, with no antihypertensive treatment for at least 3 months before inclusion (Untreated Group). Dyslipidemia was evaluated and cardiovascular risk stratification was performed according to ESC/ESH guidelines. RESULTS: More than half of the treated and untreated subjects were classified into high or very high cardiovascular risk groups. In a total of 1817 patients, the percentage of patients in "high" plus "very high" added risk groups increased to 55.2% in Treated Referral Group (p < 0.001), to 62.6% in Untreated Referral Group (p = 0.25) and to 60.7% in Untreated Primary Care Group (p < 0.001), by re-evaluation of patients' lipid values. CONCLUSIONS: Serum lipid levels are useful in stratifying hypertensive patients into cardiovascular risk groups more accurately, for appropriate antihypertensive treatment.

Comparison of early dobutamine stress echocardiography and exercise electrocardiographic testing for management of patients presenting to the emergency department with chest pain.

This study compared the cost-effectiveness of dobutamine-atropine stress echocardiography (DASE) and electrocardiographic exercise testing (EET) implemented in emergency department accelerated diagnostic protocols for the early stratification of low-risk patients presenting with acute chest pain (ACP). One hundred ninety-nine patients with ACP, nondiagnostic electrocardiographic results, and negative biomarker results were randomized to DASE (n = 110) or EET (n = 89) <6 hours after emergency department presentation. Patients with negative risk assessment results were immediately discharged and followed for 2 months. Ninety patients (82%) in the DASE arm and 78 (88%) in the EET arm were discharged after the diagnosis of nonischemic ACP. The mean lengths of stay in the hospital were 23 +/- 12 and 31 +/- 23 hours in the DASE and EET arms, respectively (p = 0.01). No 2-month follow-up events occurred in DASE patients, and the event rate was significantly higher in EET patients (0% vs 11%, p = 0.004). The DASE strategy showed lower costs compared with the EET strategy at 1-month ($1,026 +/- $250 vs $1,329 +/- $1,288, p = 0.03) and 2-month ($1,029 +/- 253 vs $1,684 +/- $2,149, p = 0.005) follow-up. In conclusion, early DASE in emergency department triage of low-risk patients with ACP is safe and reduces costs of care compared to EET.

Evaluation of the metabolic syndrome in hypertensive patients: results from the ICEBERG Study.

The Intensive/Initial Cardiovascular Examination Regarding Blood Pressure Levels: Evaluation of Risk Groups (ICEBERG) study was aimed at evaluating the components of the metabolic syndrome (MS) for cardiovascular risk stratification in hypertensive patients. The ICEBERG study consisted of 2 subprotocols: ICEBERG-1, conducted at 20 university hospitals, and ICEBERG-2, conducted at 197 primary health care centers. Each subprotocol had 2 patient profiles: patients diagnosed with hypertension and receiving medical treatment (treated group) and patients who had not received antihypertensive treatment (untreated group). MS was defined in the Third Report of the National Cholesterol Education Program Adult Treatment Panel as the presence of at least 3 of the following abnormalities: decreased plasma high-density lipoprotein cholesterol level, increased plasma triglyceride level, hypertension, increased fasting glucose level, and obesity. In a total of 4039 patients, 65.0% had MS, 30.2% had 3 components, 15.0% had 2 components, and 24.8% had 4 components. The most common accompanying component to hypertension was abdominal obesity. Therefore, this study underlined the value of questioning metabolic components in patients with high-normal or high blood pressure to identify individuals with high added risk of cardiovascular disease.

The impact of plasma high-sensitivity C-reactive protein levels on cardiovascular risk stratification of hypertensive patients: results of the ICEBERG study.

The Intensive/Initial Cardiovascular Examination Regarding Blood Pressure Levels: Evaluation of Risk Groups (ICEBERG) study focused on the impact of high-sensitivity C-reactive protein (hs-CRP) measurement on cardiovascular risk evaluation. The ICEBERG study comprised 2 subprotocols. Each subprotocol had 2 patient profiles: patients previously diagnosed with essential hypertension and under medical treatment and patients with systolic blood pressure 130 mm Hg or higher, or diastolic blood pressure 85 mm Hg or higher, with no treatment for at least 3 months before inclusion. Measurement of hs-CRP and cardiovascular risk stratification were performed according to European Society of Hypertension/European Society of Cardiology (ESH/ESC) guidelines. A total of 1817 patients were analyzed. In 1 group, the percentage of patients in "high" plus "very high" added-risk groups increased from 59.2% to 72.7% when hs-CRP data were added to routine serum biochemistries. In another, the increase was from 66.9% to 77.9%, whereas in a third group, it changed from 65.1% to 77.2%. The use of plasma hs-CRP levels might help in stratifying hypertensive patients into specific risk groups and modifying preventive approaches.

Intensive cardiovascular examination regarding blood pressure levels: evaluation of risk groups. ICEBERG study.

OBJECTIVE: Assessment of total cardiovascular risk level is crucial for approaching hypertensive patients. Therefore, the aim of the Intensive/Initial Cardiovascular Examination regarding Blood pressure levels: Evaluation of Risk Groups (ICEBERG) study is to determine cardiovascular risk evaluation and stratification of subjects with high normal and high blood pressure (BP > or = 130/85 mmHg), and to evaluate the impact of laboratory tests on this stratification. METHODS: ICEBERG was an epidemiological study conducted at 20 university hospitals and 197 primary healthcare centers. A total of 10,313 patients, who were diagnosed with high BP and under antihypertensive treatment or not antihypertensive under treatment at least for the last 3 months were selected. Besides routine clinical evaluation, microalbuminuria (MAU) and high sensitive C-reactive protein (hs-CRP) tests, echocardiography (Echo) and carotid ultrasonography (USG) were performed in selected arms. The patients were stratified into low, moderate, high and very high added risk groups as described by the European Society of Hypertension/European Society of Cardiology Guidelines Committee (2003). RESULTS: Upon routine evaluation, the percentage of "high and very high added cardiovascular risk" groups was between 51.2% and 60.7% in different study arms. This percentage increased to 62.9% by subsequent serum biochemistry assessment and to 76.2% by hs-CRP test results. Switching upwards to "high and very high added risk" groups was around 6% when MAU results were used, with a 4.9% upwards switch to "high and very high added risk" groups when Echo was performed; this proportion increased by 6.8%, when carotid USG was taken into account. CONCLUSION: Cardiovascular risk evaluation by intensive cardiovascular examination including Echo and carotid USG provided more accurate risk stratification. Furthermore, a simple test to demonstrate presence of MAU usable at primary healthcare level will also help to evaluate the patient's risk profile better than routine assessment methods alone.

Effect of irbesartan monotherapy compared with ACE inhibitors and calcium-channel blockers on patient compliance in essential hypertension patients: a multicenter, open-labeled, three-armed study.

OBJECTIVES: This multicenter, three-armed, open-labeled study investigated patient compliance of patients receiving irbesartan, angiotensin-converting enzyme (ACE) inhibitors or calcium-channel blockers (CCB) for essential hypertension for a 6-month period. Patients were either newly diagnosed or switched from existing antihypertensive medication due to lack of efficacy or side-effects. METHODS: Patients were started monotherapy with irbesartan (n=377), ACE inhibitors (n=298) or CCB (n=308) and were reevaluated on 1st, 3rd, and 6th months of the treatment. The primary endpoint was patient compliance, assessed by proportion of patients who had taken their study medication every day. Efficacy was recorded as mean reductions in blood pressure and the proportion of patients whose blood pressure normalized. Tolerability was assessed by reported adverse events. RESULTS: Significantly more patients receiving irbesartan had complied with study medication after 3 and 6 months of treatment than ACE inhibitors or CCB. Significantly fewer patients receiving irbesartan needed to change their antihypertensive medication. All three study treatments exhibited similar efficacy profiles, but irbesartan had significantly less adverse events. CONCLUSIONS: This study demonstrated that patient compliance to irbesartan was significantly superior to other study treatments. Irbesartan is therefore a suitable first-line therapy for essential hypertension in everyday clinical practice.