The use of single-pill combinations as first-line treatment for hypertension: translating guidelines into clinical practice.

: The 2008 European Society of Cardiology/European Society of Hypertension guidelines recommend the first-line prescription of two antihypertensive drugs in single-pill combinations (SPCs), also known as fixed-dose combinations, for the treatment of most patients with hypertension. This recommendation is based on a large amount of data, which shows that first-line treatment with SPCs supports reaching blood pressure targets rapidly and reducing cardiovascular outcome risk while keeping the therapeutic strategies as simple as possible and fostering adherence and persistence. As this approach constitutes a big shift from the stepped-care approaches that have been dominant for many years, practicing physicians have expressed concerns about using SPCs as first-line agents. In this review, we will discuss the barriers to the uptake of this recommendation. We will also offer suggestions to reduce the impact of these barriers and address specific concerns that have been raised.

Arterial stiffness mediates the effect of salt intake on systolic blood pressure.

Accumulating evidence indicates that higher levels of salt intake are associated with higher blood pressure levels. The aim of our analysis was to test the hypothesis that the effect of urinary sodium excretion (UNaV) on systolic blood pressure (SBP) is mediated through estimated glomerular filtration rate (eGFR) and arterial stiffness and also to test the direction of the relationship between eGFR and arterial stiffness, in both hypertensive and normotensive patients. We assessed the potential for connection between UNaV and SBP and mediators (eGFR and pulse wave velocity [PWV]) of this relationship using structural equation models of data from 1599 adults ≥18 years of age and without chronic kidney disease who participated in the Third Epidemiologic Study concerning the Prevalence of Arterial Hypertension and Cardiovascular Risk in Romania (SEPHAR III). In hypertensive patients, the indirect effect, mediated through PWV, of UNaV on SBP was 23.9% and 27.7% of the total effect of UNaV on SBP, while in normotensive patients the contribution of PWV to the total effect of UNaV on SBP was slightly lower (15.9% and 18.3% of the total effect of UNaV on SBP). Taken together, our findings support the conclusion that UNaV influences SBP, both directly and indirectly, through the effect on PWV.

Serum uric acid and arterial hypertension-Data from Sephar III survey.

OBJECTIVES: This paper aims to evaluate the association between serum uric acid (SUA) levels, arterial hypertension (HT) prevalence, blood pressure values control, kidney function and intima media thickness (IMT), as a surrogate marker of early atherosclerosis, in a representative group of Romanian adult population. MATERIALS AND METHODS: The study sample consists in 1920 adults included in SEPHAR III (Study for the Evaluation of Prevalence of Hypertension and cArdiovascular Risk in Romania) survey (mean age 48.63 years, 52.76% females) collecting data for SUA levels, blood pressure (BP) measurements, kidney function by estimated glomerular filtration rate (eGFR) and carotid IMT. SUA levels between 2,40-5,70mg/dl in females and 3,40-7,00mg/dl in males respectively were considered normal. HT and HT control were defined according to the current guidelines. IMT evaluation was assessed by B-mode Doppler ultrasound evaluation. RESULTS: Hypertensive subjects had significantly higher values of SUA compared with normotensive subjects, hypertensive patients were 1.713 times more likely to have higher values of SUA. Among treated hypertensive patients, those without optimal BP control had significantly higher SUA levels compared with those with optimal BP control, the presence of hyperuricemia increasing the odds of suboptimal BP control by 1.023. Hyperuricemic subjects had significantly lower eGFR values compared with normouricemic ones, on an average with 14.28ml/min/1.73m2 by Modification of Diet in Renal Disease formula (MDRD) and with 16.64ml/min/1.73m2 by Chronic Kidney Disease Epidemiology Collaboration formula (CKD-EPI), with an indirect association between SUA levels and eGFR values (rs = -0.319 / -0.347), independent of age. IMT values recorded in hyperuricemic subjects were significantly increased, on an average with 0.08mm, compared with normouricemic subjects, with a direct association between SUA levels and IMT values (rs = 0.263), independent of BP values. CONCLUSION: The results of our study offers support that increased SUA levels are associated with arterial hypertension and with suboptimal BP control in treated hypertensive subjects. The decline in kidney function, independent of age, and also increased IMT values as a marker of atherosclerosis, were also correlated with elevated SUA values. Hyperuricemia screening may have a role in identifying patients at risk of developing HT and lowering SUA levels may improve not only BP control in treated HT patients but also decrease total cardiovascular mortality by slowing the progression of atherosclerosis and renal failure in hypertensive patients.

Perspectives on hypertension's prevalence, treatment and control in a high cardiovascular risk East European country: data from the SEPHAR III survey.

OBJECTIVES: To estimate the trend in arterial hypertension's prevalence, awareness, treatment, and control in Romania, starting from the latest national survey Study for the Evaluation of Prevalence of Hypertension and Cardiovascular Risk in Romania III that has a crucial importance for the development of prevention strategies at national level. METHODS: A representative sample of 1970 Romanian adults (mean age 48.38 years, age range 18-80 years, 52.5% women, 72.58% response rate), was enrolled. During the two study visits, three blood pressure (BP) measurements were performed at 1-min interval. Hypertension was defined as study SBP at least 140 mmHg and/or study DBP at least 90 mmHg at both study visits or previously diagnosed hypertension, regardless of BP values. BP control was defined as SBP less than 140 mmHg and DBP less than 90 mmHg in hypertensive patients. RESULTS: General hypertension prevalence is 45.1% (19.1% newly diagnosed hypertension, 80.9% awareness of hypertension), increasing with age, regardless of sex and area of residence. Although the majority (72.2%) of hypertensive patients were treated (51.9% with two or more drugs), only 30.8% of them had controlled BP values. Following the evolution from the last 11 years, it is expected that in 2020 the prevalence of hypertension to be up to 44%, the awareness up to 96.2%, treatment of hypertension up to 83.7%, and BP control up to 36.6%. CONCLUSION: Hypertension's prevalence in Romania is on the rise despite the increase in awareness, treatment, and control. Possible explanations of this trend might be the increasing incidence of unhealthy lifestyle and diet, including high salt intake, and a general increase in the prevalence of obesity, diabetes mellitus, and dyslipidemia.

Factors associated with use of percutaneous coronary intervention among elderly patients presenting with ST segment elevation acute myocardial infarction (STEMI): Results from the ISACS-TC registry.

BACKGROUND: A substantial proportion of elderly with ST segment elevation myocardial infarction (STEMI) do not undergo percutaneous coronary intervention (PCI). We sought to investigate factors associated with the decision not to perform coronary angiography at admission in these patients. METHODS: We evaluated 1315 STEMI patients aged ≥75years old enrolled in the International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS TC) registry between October 2010 and February 2015. They were compared with 6667 patients aged <75years old enrolled in the registry in the same time frame. RESULTS: Elderly patients were less likely to undertake invasive coronary evaluation compared with younger patients (62.1% vs. 78.9; p<0.001%). In the older group there were a lower proportion of patients presenting <12h after symptom onset (66.5% vs.76.9%, p<0.001), and a higher prevalence of comorbidities. Few elderly were treated with current recommended evidence based treatments (aspirin, clopidogrel, heparins, beta-blocker, statins, and ACE-inhibitors). Logistic analysis adjusted for age and sex showed that older age was associated with underuse of coronary angiography (OR 0.46, 95% CI: 0.41-0.53, p<0.001). Clinical factors that were associated with underuse of angiography in patients over 75 were: female sex (OR: 0.77), presence of comorbidities (OR: 0.91), anemia (OR: 0.44) and late hospital admission (OR: 0.89). CONCLUSIONS: In the ISACS-TC, more than one third of the elderly with STEMI did not undergo coronary angiography at admission. Sex, comorbidities, and late hospital admission were independent factors associated with the underuse of PCI in these patients.

Hypertension and Ischemic Heart Disease in Women.

BACKGROUND: Ischemic heart disease (IHD) is the most important cause of mortality worldwide. Although the awareness of cardiovascular risk factors and IHD in women has increased over the last decades, mortality rates are still higher in women than in men. Among traditional cardiovascular risk factors, hypertension is associated with a greater risk for IHD in women as compared to men. METHODS: In this review, discuss gender differences in epidemiology and pathophysiology of hypertension and its impact on the incidence and outcomes of IHD in women. We also, discuss some "women conditions" such as hypertensive disorders in pregnancy (HDP) and polycystic ovarian syndrome (PCOS). Even though this is not a systematic review, English-language studies on MEDLINE and the Cochrane Database of Systematic reviews were searched for consultation and analysis. RESULTS: Hypertension display different epidemiological patterns in men and women. Studies have shown that hypertension has a different proatherogenic effects in men and women. Hypertension has a direct effect on microcirculation, but estrogens have a protective role in this regard in premenopausal women. However, after the decline in estrogen levels, women are exposed to the same cardiovascular risk as males. Postmenopausal women exhibit a greater burden of cardiovascular risk factors, which together with microvascular dysfunction and smaller and stiffer arteries conducts to the worse prognosis observed in women with IHD. "Women specific conditions" such as HDP and PCOS affects 10% of pregnant women and women in reproductive age, respectively. These conditions are associated with increased risk of hypertension and IHD later in life. Although women are more aware of their hypertension, cardiovascular mortality is higher in hypertensive women with comorbid IHD. Yet these gender disparities in outcomes seem to be attenuated with effective therapy. CONCLUSION: The pathophysiology of IHD is gender specific, women with ischemic symptoms presenting less often with coronary obstructive disease, and more frequently with dysfunction of the coronary microcirculation. Optimal control of hypertension could attenuate gender related differences in mortality in this population.

Prognostic Value of Right Ventricular Function Assessed by Echocardiography in Patients Presenting With a First Acute ST Elevation Myocardial Infarction Treated By Primary PCI.

Aims: Informations regarding the prognostic value of right ventricular function changes in the setting of a first acute ST elevation myocardial infarction irrespective of the site of the necrosis and of the left ventricular systolic function are scarce. Purpose of the study was to assess the relation between parameters reflecting global and systolic right ventricular function assessed by conventional, speckle tracking and three-dimensional echocardiography and in hospital major cardiac events (MACE). Materials and Methods: We have prospectively analyzed a cohort of 44 consecutive patients (mean age 62,71 years, 70.5 % males) presenting with a first STEMI (2,3 % Topol 1, 38 ,6 % Topol 2, 20,6 % Topol 3, 31,8 % Topol 4, 6,8 % Topol5) treated by primary angioplasty. Patients with previous history of cardiac or pulmonary diseases were excluded. All patients underwent during hospitalization conventional 2D echocardiography and special techniques ( 2D speckle tracking echocardiography and also 3D echocardiography) RV global function was quantified by RV myocardial performance index (RV MPI) determined by PW Doppler ,whereas RV systolic function was studied using regional parameters like TAPSE , pulsed Doppler S wave and RV free wall 2D strain and global parameters like RV fractional area change (RV FAC) or RV ejection fraction ( RVEF) determined by 3D echocardiography . LV systolic function was described by LV ejection fraction (LVEF). The combined endpoint of major adverse cardiovascular events (MACE) was defined by all cause mortality, reinfarction, need for revascularization and occurrence of heart failure during hospitalization. The association between MACE and RV functional parameters was assessed by bivariate correlation analysis followed by binary logistic regression. Results: Initially, regardless of the site of necrosis, the only RV functional parameter correlated with MACE was RV MPI (OR 9.17; 95% CI: 1.03 -83.7). After adjustment for LVEF all RV functional parameters were correlated with MACE: TAPSE (OR: 1.83; 95% CI : 0.41- 8.23), RV MPI (OR: 8.07; 95% CI : 0.9- 72.07), RVFAC (OR: 1.22; 95% CI : 0.25- 5.98) , RV free wall strain (OR : 1.04; 95% CI : 0.21- 5.08) , S wave (OR: 2.46 ; 95% CI : 0.14- 42.82), RVEF (OR: 0.83 ; 95% CI : 0.20- 3.43). Conclusions: Our study reveals that RV functional parameters are predictive for in hospital MACE beyond LV systolic function and regardless of the culprit coronary artery. Among these parameters, RV MPI seems to have the greatest predictive value for short term MACE in STEMI patients.

Cognitive impairment in manic bipolar patients: important, understated, significant aspects.

BACKGROUND: Bipolar disorder is a chronic mood disorder with episodic progress and high relapse rate. Growing evidence suggests that individuals with bipolar disorder display cognitive impairment which persists even throughout periods of symptom's remission. METHOD: 137 bipolar patients met the inclusion criteria (depressive episode: DSM-IV-TR criteria for major depressive episode, HAMD score ≥17; manic/hypomanic episode: DSM-IV-TR criteria for manic/hypomanic episode, YMRS score ≥12, euthymic: 6 months of remission, HAMD score ≤8, YMRS score ≤6; and mixed: DSM-IV-TR criteria for mixed episode, HAMD score >8 and YMRS score >6) and were therefore enrolled in the study. Patients were free of psychotic symptoms (hallucinations/delusions) at the moment of testing. Control group consisted of 62 healthy subjects without history of neurological and/or psychiatric disorder. Cognitive battery has been applied in order to assess verbal memory, working memory, psychomotor speed, verbal fluency, attention and speed of information processing, and executive function. Following data were collected: demographics, psychiatric history, age of illness onset; current and previous treatment (including hospitalizations). Cognitive deficits were assessed in bipolar patients experiencing manic, depressive, mixed episodes or who were euthymic in mood. Results were compared between the subgroups and with healthy individuals. The association of impaired cognition with illness course was analyzed. RESULTS: Bipolar patients showed cognitive deficits in all evaluated domains when compared to controls. The lowest scores were obtained for the verbal fluency test. After adjusting for current episode, manic subgroup showed greater cognitive impairment in verbal and working memory, executive function/reasoning and problem solving, compared to depressive, mixed, and euthymic subgroup. Low-neurocognitive performance was directly associated with a predominance of manic episodes and severe course of bipolar illness. An increased number of past manic episodes was the strongest correlated event with the poorest outcomes in verbal memory testing. Other factors correlated with poor verbal memory scores in manic subgroup were age at illness onset (positive correlation), illness length, and hospitalizations (negative correlations). CONCLUSIONS: Bipolar patients showed cognitive deficits regardless of the phase of illness. Subjects experiencing a manic episode displayed higher deficits in verbal and working memory, executive function/reasoning, and problem solving. Severe course of illness also showed significant contribution in terms of cognitive impairment.

Objectives and methodology of Romanian SEPHAR II Survey. Project for comparing the prevalence and control of cardiovascular risk factors in two East-European countries: Romania and Poland.

INTRODUCTION: Comparing results of representative surveys conducted in different East-European countries could contribute to a better understanding and management of cardiovascular risk factors, offering grounds for the development of health policies addressing the special needs of this high cardiovascular risk region of Europe. The aim of this paper was to describe the methodology on which the comparison between the Romanian survey SEPHAR II and the Polish survey NATPOL 2011 results is based. MATERIAL AND METHODS: SEPHAR II, like NATPOL 2011, is a cross-sectional survey conducted on a representative sample of the adult Romanian population (18 to 80 years) and encompasses two visits with the following components: completing the study questionnaire, blood pressure and anthropometric measurements, and collection of blood and urine samples. RESULTS: From a total of 2223 subjects found at 2860 visited addresses, 2044 subjects gave written consent but only 1975 subjects had eligible data for the analysis, accounting for a response rate of 69.06%. Additionally we excluded 11 subjects who were 80 years of age (NATPOL 2011 included adult subjects up to 79 years). Therefore, the sample size included in the statistical analysis is 1964. It has similar age groups and gender structure as the Romanian population aged 18-79 years from the last census available at the moment of conducting the survey (weight adjustments for epidemiological analyses range from 0.48 to 8.7). CONCLUSIONS: Sharing many similarities, the results of SEPHAR II and NATPOL 2011 surveys can be compared by a proper statistical method offering crucial information regarding cardiovascular risk factors in a high-cardiovascular risk European region.

Visit-to-Visit Blood Pressure Variability and Arterial Stiffness Independently Predict Cardiovascular Risk Category in a General Population: Results from the SEPHAR II Study.

INTRODUCTION: The aim of our study was to evaluate visit-to-visit blood pressure variability (BPV) and the association of this parameter with cardiovascular risk determinants, according to the SEPHAR II survey. METHODS: Following a selection based on the multi-stratified proportional sampling procedure, a total of 1975 subjects who gave informed consent were evaluated by means of a questionnaire, anthropometric, blood pressure (BP) and arterial stiffness measurements (pulse wave velocity and augmentation index), 12-lead ECG recordings, and blood and urine analysis. BPV was quantified in terms of the standard deviation (SD) of the mean systolic blood pressure (SBP) and high BPV was defined as SBP-SD above the 4th quartile. Total cardiovascular risk was assessed by the 2013 ESH/ESC risk stratification chart. RESULTS: Mean BP was 132.37/82.01 mmHg. Mean systolic BPV was 6.16 mmHg, with 24.62% of values above the 75th percentile (8.48 mmHg). Factors found to be associated with high systolic BPV were age, SBP, pulse pressure, total and LDL-cholesterol, triglycerides, visceral obesity, diabetes mellitus, metabolic syndrome and increased aortic stiffness. In addition, in the hypertensive group high BPV was associated with the severity of hypertension and a lack of treatment control. Both visit-to-visit systolic BPV and aortic stiffness proved to be positively and independently correlated with the risk category. Based on these parameters it was possible to predict with 72.6% accuracy the probability of finding subjects in a high and very high cardiovascular risk category. CONCLUSIONS: The results of our study indicate a notable prevalence of high BPV, affecting almost a quarter of the Romanian adult population. Visit-to-visit systolic BPV and arterial stiffness are strongly correlated and together might contribute to the improvement of cardiovascular risk prediction models.

Hypertension prevalence and control in Romania at a seven-year interval. Comparison of SEPHAR I and II surveys.

OBJECTIVES: To present the current epidemiologic situation regarding hypertension's prevalence and control in Romania's adult population (revealed by SEPHAR II survey results) and to evaluate their tendency during the last 7 years (by comparing with the SEPHAR I survey results). METHODS: The two SEPHAR cross-sectional national surveys were conducted on a representative sample for the Romanian adult population (SEPHAR I: 2017 individuals aged 18-85 years, 45% response rate, SEPHAR II: 1975 individuals aged 18-80 years, 69% response rate), by means of questionnaire interview, blood pressure (BP) and anthropometric measurements during two study visits. Hypertension was defined as SBP at least 140  mmHg and/or DBP at least 90  mmHg at both study visits or previously diagnosed hypertension under current treatment. Controlled BP was defined as SBP less than 140  mmHg and DBP less than 90  mmHg in currently treated hypertensive individuals. RESULTS: Prevalence of hypertension in Romanian is 40.41%, awareness of hypertension is 69.55%, with 59.15% hypertensive individuals under current treatment with a control rate of 25%. In the last 7 years, there has been a 10.7% decrease in hypertension's prevalence together with an increase by 57% in awareness of hypertension and an increase by 52% in treatment of hypertension, leading to almost doubling of the hypertension's control rate in all hypertensive individuals. CONCLUSION: Although in the last 7 years, the tendency of hypertension's prevalence seems to be a descending one with an increasing trend in awareness, treatment and control of this condition, hypertension in Romania at this time still remains an 'unsolved equation'.

New cardiovascular risk factors and their use for an accurate cardiovascular risk assessment in hypertensive patients.

OBJECTIVES: To analyze the predictive value of new cardiovascular (CV) risk factors for CV risk assessment in the adult Romanian hypertensive (HT) population. METHODS: Hypertensive adults aged between 40-65 years of age, identified in national representative SEPHAR II survey were evaluated by anthropometric, BP and arterial stiffness measurements: aortic pulse wave velocity (PWVao), aortic augmentation index (AIXao), revers time (RT) and central systolic blood pressure (SBPao), 12 lead ECGs and laboratory workup. Values above the 4th quartile of mean SBP' standard deviation (s.d.) defined increased BP variability. Log(TG/HDL-cholesterol) defined atherogenic index of plasma (AIP). Serum uric acid levels above 5.70 mg/dl for women and 7.0 mg/dl for males defined hyperuricemia (HUA). CV risk was assessed based on SCORE chart for high CV risk countries. Binary logistic regression using a stepwise likelihood ratio method (adjustments for major confounders and colliniarity analysis) was used in order to validate predictors of high and very high CV risk class. RESULTS: The mean SBP value of the study group was 148.46±19.61 mmHg. Over forty percent of hypertensives had a high and very high CV risk. Predictors of high/very high CV risk category validated by regression analysis were: increased visit-to-visit BP variability (OR: 2.49; 95%CI: 1.67-3.73), PWVao (OR: 1.12; 95%CI: 1.02-1.22), RT (OR: 0.95; 95% CI: 0.93-0.98), SBPao (OR: 1.01; 95%CI: 1.01-1.03) and AIP (OR: 7.08; 95%CI: 3.91-12.82). CONCLUSION: The results of our study suggests that the new CV risk factors such as increased BP variability, arterial stiffness indices and AIP are useful tools for a more accurate identification of hypertensives patients at high and very high CV risk.

Profile of the Romanian hypertensive patient data from SEPHAR II study.

AIM: The objective of this paper is to present the profile of the Romanian hypertensive patient as revealed by the analysis of hypertensive subjects from SEPHAR II survey. METHODS: A total number of 798 hypertensive subjects identified by SEPHAR II survey were analyzed in terms of socio-demographic characteristics, cardiovascular risk factors, subclinical target organ damage, established target organ disease, total CV risk and HT awareness, treatment and control. The profile of the Romanian hypertensive patients was built using the mod of every above mentioned target variables. RESULTS: The majority of hypertensive subjects were females (54.9%), mean age of 57.42 +/- 13.38 years, coming from the South region (17.8%), living in urban areas (59.5%) and aware of their condition (69.5%), associating most often other 4 CV risk factors among which physical inactivity (67.3%), visceral obesity (60.4%) and hypercholesterolemia (61.3%) are the most prevalent, having therefore a very high added CV risk (60.3%). Despite the widespread use of at least 2 antihypertensive drugs (72.3%), an effective treatment was recorded only in a quarter of treated hypertensives. CONCLUSION: The profile of Romanian Hypertensive patient is: middle aged female living in urban area of the South region of the country, with secondary education and a low average income, sedentary lifestyle, nonsmoker and aware of BP values, having visceral obesity, a high total cholesterol and LDL-cholesterol levels and normal HDL-cholesterol and triglyceride levels, having metabolic syndrome, nondiabetic and associating 4 other cardiovascular risk factors and therefore having a high added cardiovascular risk.

B-Type Natriuretic Peptide (BNP) and Left Ventricular (LV) Function in Patients with ST-Segment Elevation Myocardial Infarction (STEMI).

BACKGROUND: After acute myocardial infarction (AMI), left ventricular (LV) function is a well-established prognostic marker. Recent studies indicate that serum levels of brain natriuretic peptide (BNP) also represent an prognostic marker in this setting but so far without a precise cut-off value. OBJECTIVE: The aim of this study was to assess the predictive value of BNP serum levels for LV function assessed by echocardiography in STEMI patients undergoing revascularization. METHODS: We prospectively studied a cohort of 88 consecutive patients (mean age 51.6 years, 88.6% males) hospitalized in our clinic for STEMI in Killip class I (50% anterior infarction), who underwent reperfusion therapy. Serum BNP levels were measured on admission, at 24h and at 30 days after reperfusion. Detailed echocardiography was performed at baseline, at 24 hours after reperfusion, on discharge and at follow-up at 1 month. Left ventricular systolic and diastolic dysfunction were defined by LVEF < 45% and E/A ratio respectively. RESULTS: ROC curve analysis showed that BNP measurements on admission and at 24 hours after revascularization have no predictive value neighter for diastolic LV dysfunction in anteior or inferior AMI patients, nor for systolic LV dysfunction in inferior AMI patients. Only BNP levels at 24 hours after revascularization can predict systolic LV dysfunction in anterior AMI patients with a 90.3% sensitivity and a 60% false positive rate at a cutt off value of 90pg/ml. CONCLUSIONS: Early measurement of BNP levels may allow early prediction of anterior STEMI patients at risk of developing systolic LV dysfunction after revascularization therapy.