Cardiotrophin-1 in Asymptomatic Hypertensive Patients With Mild Diastolic Dysfunction: Potential Prognostic Value in Early Stages of Hypertensive Heart Disease.

BACKGROUND: Regardless of the advancements in modern technology and treatment options, heart failure (HF) exhibits impervious mortality and morbidity rates. Arterial hypertension poses one of the greatest risks for developing HF, yet the exact pathophysiological path and changes that lead from isolated hypertension to HF are still unclear. Cardiotrophin-1 (CT-1) serves as a promising prognostic biomarker for the onset of HF in hypertensive patients. The aim of this study was to investigate whether CT-1 levels are elevated in a selected group of asymptomatic hypertensive patients. METHODS: In a selected cohort of 40 asymptomatic patients with early diastolic dysfunction (grade I), without any signs of increased filling pressures in the left ventricle, as well as 20 healthy individuals, the levels of CT-1 brain natriuretic peptide (BNP) along with various echocardiographic parameters were evaluated. RESULTS: The mean age of the hypertensive patients was 56 ± 5 years and 52± 3.5 years for the normotensive controls. The hypertensive group exhibited higher levels of CT-1, which was not affected by left ventricular hypertrophy. Notably, in patients with normal E/E' < 8 (n = 30), CT-1 levels were 1165 ± 471 pg/ml compared to 2069 ± 576 pg/ml in patients with marginal E/E' > 8 and <14 (n = 10), p = 0.001. CONCLUSIONS: Our study demonstrated elevated CT-1 levels in a cohort of asymptomatic hypertensive patients, exhibiting mild diastolic dysfunction. These findings are suggestive of the potentially prognostic value of this particular biomarker in the early stages of hypertensive heart disease.

Effects of anthracyclines on aortic distensibility in patients with lymphomas: a prospective study.

INTRODUCTION: Anthracyclines have been widely used in the treatment of haematological malignancies. Their major adverse effect is cardiomyopathy, but their effect on vascular elasticity has not been completely elucidated. The aim of the present study was to investigate the effects of anthracyclines on aortic elastic properties in patients with lymphomas. METHODS: We studied 70 patients with lymphomas, 37 males (52.9%), age 44 ± 19 years, who were free of any cardiorenal or metabolic comorbidity. Forty-five (64.2%) had a non-Hodgkin lymphoma and the remainder a Hodgkin lymphoma. All participants were evaluated with echocardiography, laboratory and clinical examinations to estimate cardiac function and aortic elasticity in the following study phases: before the administration of anthracyclines (i.e. baseline), after three months, and after the end of treatment. RESULTS: A progressive decrease in aortic distensibility was observed over the three phases of the study (2.48 ± 0.2 vs. 2.41 ± 0.18, vs. 2.36 ± 0.23, 10(-6).dyn(-1).cm(2); p<0.016 for all comparisons). A statistically significant decrease in left ventricular ejection fraction was also observed between baseline and final follow up. Significant negative predictors of aortic distensibility at final follow up were baseline age, systolic blood pressure, left atrial diameter, and left ventricular ejection fraction. CONCLUSIONS: Anthracycline therapy decreases aortic distensibility in patients with lymphomas.

The AGT and the GNB3 polymorphisms and insulin resistance in prehypertension.

OBJECTIVE: This study surveyed the frequencies of single nucleotide polymorphisms (SNPs) M235T AGT and C825T GNB3, and their association with insulin resistance, other biochemical markers and qualitative variables in subjects with high normal blood pressure and/or prehypertension in the Greek population. DESIGN: 330 men and women of Greek origin were divided into 3 groups: a) hypertensive, b) prehypertensive and c) control group. These groups were genetically tested for these polymorphisms and insulin resistance with the HOMA index. RESULTS: No statistically significant differences were found among the polymorphisms of the compared groups. However, the ? allele carriers (CT/TT vs. CC) of the C825T polymorphism were associated with an increased BMI in all 3 groups (p=0.004). The HOMA index was higher in the hypertensive (p=0.006) and prehypertensive (p=0.016) versus the control group, and similar results were found for insulin (hypertensive vs. control p=0.012, prehypertensive vs. control p=0.001) without statistical significance between the first 2 groups (p=0.522). Additionally, there was a statistically significant difference between the control group and the hypertensive and prehypertensive groups regarding cholesterol (control vs. hypertensive p=0.001, control vs. prehypertension p=0.018) and triglycerides (control vs. hypertensive p=0.0001, control vs. prehypertension p=0.007). Differences were also noted between the control and the hypertensive group regarding the value of HDL (p=0.005) and LDL (p=0.013). CONCLUSION: This study failed to demonstrate a correlation between specific SNPs, blood pressure and insulin resistance in the 3 groups. However, T allele carriers of the polymorphism C825T were found to have an increased BMI. Similarly, increased insulin resistance and lipidemia were more common in the hypertensive and prehypertensive populations.

Stress management and dietary counseling in hypertensive patients: a pilot study of additional effect.

BACKGROUND: In Western societies, cardiovascular (CV) disease is the primary cause of mortality, and high blood pressure (BP) is the main reversible factor leading to CV disease. Dietary habits and psychosocial stress contribute to the establishment of hypertension, while its role in the control of high BP is currently examined. In this study, we examined the effect and feasibility of a combined intervention of dietary education and stress management on the control of hypertension. METHODOLOGY: A randomized, controlled pilot study was designed to evaluate the effect of combined education on stress management techniques and dietary habits (Mediterranean diet principle) on office BP after eight weeks. RESULTS: Of the 45 randomized subjects, 36 were included in the final analysis (control group = 20 (age: 67 ± 12 years, 31.8%, males) and intervention group = 16 (age: 62 ± 12 years, 47%, males)). CV disease risk factors (except smoking), BP, dietary habits, perceived stress and physical activity (all assessed with validated questionnaires) were similar between the two groups at baseline. After eight weeks, office BP (systolic and diastolic) and perceived stress were significantly reduced, whereas the adherence in Mediterranean diet principle was significantly increased, but only in the intervention group. CONCLUSIONS: A combined intervention of stress management techniques and Mediterranean diet education seems to be beneficial for BP reduction. Such interventions could possibly serve as a complementary treatment along with drug therapy or in the early treatment of high normal BP. A call to action for designing epidemiological studies and evaluating the efficacy of such non-pharmacological treatment strategies is therefore warranted.

Homocysteine levels and MTHFR polymorphisms in young patients with acute myocardial infarction: a case control study.

INTRODUCTION: Increased levels of homocysteine are known to be associated with coronary artery disease (CAD). The most common form of genetic hyperhomocysteinemia results from MTHFR polymorphisms. To examine the role of homocysteine levels and MTHFR polymorphisms in premature CAD and acute myocardial infarction (MI) in the Cypriot population, a case control study was performed in Nicosia General Hospital. METHODS: Sixty-three male patients less than 50 years old who presented with MI in Nicosia General Hospital were compared with 54 controls without CAD. Fasting homocysteine and lipids were tested within 24 hrs from admission, while MTHFR C677T and A1298C polymorphisms were also tested. RESULTS: Mean homocysteine levels were 14.5 mol/L in patients and 12.3 mol/L in controls (p=0.017). Mutant homozygous MTHFR C677T was present in 17.7% of the patients and 19.2% of the controls (p=0.838), while mutant homozygous MTHFR A1298C was found in 16.1% of patients and 13.5% of controls (p=0.690). Mean homocysteine levels were 12.6 mol/L in patients with single-vessel CAD and 15.5 mol/L in patients with multi-vessel CAD (p=0.025). Lower HDL appeared to be associated with higher levels of homocysteine with an odds ratio of 0.901, indicating that for each unit increase in HDL, the expected odds of having high homocysteine levels decreased by approximately 10%. CONCLUSIONS: Higher levels of homocysteine are associated with acute MI and multi-vessel disease in Cypriot patients under the age of 50. The existence and extent of disease are not associated with MTHFR polymorphisms. Lower HDL is associated with higher levels of homocysteine.

Quality measurement as a prerequisite for improving hypertension control in an academic medical center.

BACKGROUND: Quality of care provided by the outpatient hypertension unit of a general hospital was measured using quality indicators (QIs) derived from guidelines. HYPOTHESIS: Measuring provided quality of care is an important step for improving it. METHODS: We enrolled 1206 patients with hypertension, 626 men and 580 women, with a mean age of 55.33 ± 12.08 years. Median follow-up was 47 months (minimum: 6 months, maximum: 349 months, interquartile range). We calculated the percentage of patients who achieved the targets of controlling blood pressure (BP), total cholesterol, low- and high-density lipoprotein cholesterol, triglycerides, glucose, uric acid, potassium, sodium, creatinine clearance, Sokolow-Lyon index, and left ventricle hypertrophy in echo between the first and the last visit. Patient satisfaction and the incidence of coronary artery disease (CAD), myocardial infarction (MI), and stroke were evaluated as outcome indicators. RESULTS: The BP was controlled in 40% of patients at the end of the study, compared with 11% at the first visit. We did not manage to achieve significant improvement for other QIs. A wide range of hypertensive patients and lack of a quality improvement program are the main reasons for low control rate. During follow-up, we obtained the increased incidence of cardiovascular events by outcome indicators such as CAD, MI, and stroke. CONCLUSIONS: Quality measurement shows us that the quality of provided care needs further improvement. Although we succeeded in controlling BP in 40% of patients, we did not manage to improve the other QIs. Modifying our structure and process components, we are working on improving outcome by achieving better control of QIs.

The combined effect of aortic stiffness and pressure wave reflections on mortality in the very old with cardiovascular disease: the PROTEGER Study.

Aortic stiffness (pulse wave velocity, PWV) and pressure wave reflections (augmentation index, AI) are two interrelated markers of mortality. Their potential synergistic effect on mortality has never been studied. We sought to investigate the association as well as the combined effect of PWV and AI on mortality in a cohort (PROTEGER Study) of very old (>70 years, mean age ( ± s.d.): 85.4 ± 7.4 years). Aortic PWV and pressure wave AI were assessed by pulse wave analysis; carotid structure and cardiac function were analyzed by ultrasound. The analysis was performed in 259 patients who had all the data available. Neither PWV nor AI was, in separate, predictors of mortality (log-rank test: P=0.278 and P=0.433, respectively, Kaplan-Meier analysis). No linear association was found between PWV and AI (P=0.278). To investigate the possible synergistic effect of PWV and AI on mortality, the population was analyzed according to the tertiles of PWV and AI. Subjects with combined high PWV (third tertile) and moderate-to-high AI (second and third tertiles) had lower survival compared with the rest of the population (Kaplan-Meier survival curve, log-rank test: P=0.030). Cox regression analysis showed that this effect was independent from age, gender, blood pressure, cardiac/carotid parameters and other confounders, except creatinine and insulin resistance. The present study provides further insight on the pathophysiological association between large artery stiffness and pressure wave reflections, suggesting that when both are elevated they may increase the mortality in the elderly.

Diabetic cardiomyopathy: from the pathophysiology of the cardiac myocytes to current diagnosis and management strategies.

Diabetic cardiomyopathy (DCM), although a distinct clinical entity, is also a part of the diabetic atherosclerosis process. It may be independent of the coexistence of ischemic heart disease, hypertension, or other macrovascular complications. Its pathological substrate is characterized by the presence of myocardial damage, reactive hypertrophy, and intermediary fibrosis, structural and functional changes of the small coronary vessels, disturbance of the management of the metabolic cardiovascular load, and cardiac autonomic neuropathy. These alterations make the diabetic heart susceptible to ischemia and less able to recover from an ischemic attack. Arterial hypertension frequently coexists with and exacerbates cardiac functioning, leading to the premature appearance of heart failure. Classical and newer echocardiographic methods are available for early diagnosis. Currently, there is no specific treatment for DCM; targeting its pathophysiological substrate by effective risk management protects the myocardium from further damage and has a recognized primary role in its prevention. Its pathophysiological substrate is also the objective for the new therapies and alternative remedies.

Increased left ventricular arrhythmogenicity in metabolic syndrome and relationship with myocardial performance, risk factors for atherosclerosis, and low-grade inflammation.

Metabolic syndrome (MetS) is a clustering of cardiovascular risk factors recently associated with left ventricular dysfunction. Limited data exist on the association between MetS and ventricular arrhythmogenicity. This study examined differences in ventricular arrhythmogenicity assessed by classic (QT interval) and newer (spatial QRS-T angle [spQRS-Ta]) electrocardiographic markers in subjects with and without MetS. A total of 306 subjects, 153 with and 153 without MetS, matched for sex and age were examined. The spQRS-Ta, which vectorcardiographically quantifies the deviation between the directions of ventricular depolarization and repolarization, was measured using a computer-based electrocardiograph. Left ventricular mass index and myocardial performance were evaluated echocardiographically. The spQRS-Ta was significantly higher in subjects with in comparison with those without MetS. Left ventricular mass index, QT interval, and its dispersion were not different between the 2 groups. Left ventricular myocardial performance was worse in subjects with MetS and was associated with higher values of the spQRS-Ta. Multivariate linear regression analysis demonstrated MetS status as the strongest predictor of ventricular arrhythmogenicity. Addition of the high-sensitivity C-reactive protein in the model increased the explained variance of the spQRS-Ta by 11%. In conclusion, ventricular arrhythmogenicity is present in MetS and is associated with myocardial dysfunction, risk factors for atherosclerosis, and low-grade inflammation. The independent association between the spQRS-Ta and MetS implies that the clustering of the metabolic disturbances has additional prognostic information than its individual components in terms of ventricular arrhythmogenicity and may explain in part the excess cardiovascular risk in subjects with MetS.

Epistaxis of patients admitted in the emergency department is not indicative of underlying arterial hypertension.

OBJECTIVE: To assess the association between epistaxis and arterial hypertension. METHODS: A prospective study was conducted in 80 patients admitted in the emergency department, 42 with epistaxis and 38 well-matched controls. Blood pressure was measured upon admission and by continuous 24-hour ambulatory monitoring on the following days. RESULTS: Estimated values upon admission did not differ between groups. A definitive diagnosis of hypertension was set in 18 patients admitted for epistaxis (42.9%) and in 11 controls (28.9%, p = NS). Systolic pressures during the 24-hour recording period, systolic pressures during day and diastolic pressures during night were significantly higher among patients admitted for epistaxis than among controls. CONCLUSIONS: Although studies with larger series of patients are mandatory, epistaxis does not seem to result from underlying arterial hypertension.

QT dispersion: comparison between diabetic and non-diabetic individuals and correlation with cardiac autonomic neuropathy.

INTRODUCTION: The QT interval on the resting electrocardiogram (ECG) expresses the myocardial depolarisation and repolarisation time. Elevated values of QT dispersion (QTd) are associated with cardiovascular mortality in diabetics. Cardiac autonomic neuropathy (CAN) is a common complication of diabetes that is also associated with increased morbidity and mortality. However, there are no data in the literature concerning the relation between CAN and QTd in diabetics. The aim of this study was to investigate: 1) the differences in QTd between diabetics and non-diabetics; 2) the differences in QTd between those with type 1 and type 2 diabetes; 3) the relation between QTd and CAN. METHODS: The study population included 184 diabetics (63 type 1, group D1; 121 type 2, group D2) and 100 healthy controls who had similar age and sex distribution to D1 (n=44) and D2 (n=56) subjects. CAN assessment was made using the standard Ewing and Clarke tests. The QT interval was measured on the 12-lead resting ECG. QTd was calculated automatically using special software. RESULTS: QTd values did not differ significantly between controls and D1 (p=0.15) or D2 (p=0.27). QTd was significantly greater in D2 than in D1 (p=0.02). There was no significant difference in QTd between those with and without CAN in either group of diabetics. CONCLUSIONS: QTd values do not differ between individuals with and without diabetes. Type 2 diabetes is associated with higher QTd values than is type 1 diabetes. CAN does not affect QTd in diabetics.

QT dispersion: comparison between participants with Type 1 and 2 diabetes and association with microalbuminuria in diabetes.

BACKGROUND AND AIMS: The interlead variation of QT duration in surface electrocardiogram [ECG; QT dispersion (QTd)] has been shown to predict mortality in both diabetic and general population. Diabetic cardiac autonomic neuropathy (CAN) is a common complication of diabetes, and it is also associated with worse prognosis among the diabetic population. In this study, we investigated the association between QTd duration and CAN, as well as other complications of diabetes in participants with Types 1 and 2 diabetes. METHODS: A total of 184 patients with either Type 1 (n=63) or 2 (n=121) diabetes, as well as 100 control participants, matched for age and sex with the diabetic individuals, were studied. QT and RR intervals were measured on 12 leads of resting ECG tracing. QTd was calculated semiautomatically using a computer program as the difference between the maximum and the minimum QT in any of the 12 leads. CAN was diagnosed when two out of the four classical tests were abnormal. RESULTS: QTd was not significantly different between controls and patients with either Type 1 or 2 diabetes. Age-adjusted QTd intervals were not significantly different between patients with Types 1 and 2 diabetes (P=.86). For both types of diabetes, no significant differences were found in QTd between patients with and without CAN. Multivariable linear regression analysis, after adjustment for a number of confounding factors, demonstrated a positive association between QTd and duration of diabetes (P=.02) in the group of the patients with Type 1 diabetes. In those with Type 2 diabetes, QTd was associated with age (P=.006) and presence of microalbuminuria (P=.001). In addition, no significant association was found with retinopathy or blood pressure levels. CONCLUSIONS: Age-adjusted QTd interval was not different between patients with Types 1 and 2 diabetes. CAN is not associated with QTd interval in both types of diabetes. Furthermore, microalbuminuria was found to be the strongest predictor of QTd in patients with Type 2 diabetes. Because long QTd interval predicts cardiac mortality in participants with diabetes, it is suggested that it may be a useful adjuvant index in the evaluation of cardiovascular risk in participants with Type 2 diabetes and microalbuminuria.