Beneficial effects of low-dose aspirin on aortic stiffness in hypertensive patients.

While treatment with low-dose aspirin has been established as a therapeutic tool for secondary prevention, the role of aspirin on primary prevention remains controversial. Aortic stiffness and wave reflections are independent predictors of cardiovascular events. The aim of the present study was to investigate the effect of low-dose aspirin on aortic stiffness and wave reflections in hypertensive patients. We studied 30 patients with grade I hypertension. Fifteen patients were treated with 160 mg of aspirin and 15 patients with placebo. Aortic stiffness and wave reflections were assessed by measuring carotid-femoral pulse wave velocity (PWV) and heart rate-adjusted augmentation index (AIx75), respectively. All measurements were conducted at baseline and 2 weeks after treatment. In the aspirin group, there was a significant reduction in PWV compared to the placebo group (from 8.9±1.5 to 8.5±1.6 m/s for the aspirin group vs from 8.6±1.4 to 8.7±1.6 m/s for the placebo group, net change: -0.5 m/s; p=0.02). AIx75 showed a marginal decrease (from 28.0±5.4 to 26.2±5.0% for the aspirin group vs from 31.2±9.7 to 30.6±9.2% for the placebo group, net change: -1.2%; p=0.06). In conclusion, a 2-week course of aspirin administration has a favorable effect on aortic stiffness and, to a lesser extent, on wave reflections in hypertensive patients. Whether the reduction in arterial stiffness is translated to fewer cardiovascular events needs to be confirmed by future prospective studies.

Dietary Guidance for Cardiovascular Health: Consensus and Controversies.

Healthy diet, regular exercise and smoking cessation comprise the 'golden triad' of primary prevention of cardiovascular disease (CVD) [...].

Value of real-time three-dimensional adenosine stress contrast echocardiography in patients with known or suspected coronary artery disease.

AIM: The aim of this study was to evaluate the feasibility of myocardial wall-motion and perfusion assessment using contrast echocardiography during real-time three-dimensional (RT3D) adenosine stress test, and compare its diagnostic accuracy with the two-dimensional (2D) method using coronary angiography as reference. METHODS AND RESULTS: Patients with known or suspected coronary artery disease (CAD) have been submitted to adenosine stress contrast echocardiography and coronary angiography, within a 1-month period. Two-dimensional apical four, two, and three chamber, as well as three-dimensional (3D) pyramidal full-volume data sets were acquired at rest and at peak stress. The 17-segment division of the left ventricle was used and each segment was evaluated based on wall motion and perfusion. Sixty patients (age: 60.1 ± 8.5 years, 38 men) were enrolled, i.e. 1020 segments were evaluated at rest and at peak stress. Wall-motion analysis per patient revealed that the sensitivity and specificity of 2D to detect CAD were 80 and 82% and of RT3D echocardiography were 82 and 64%, respectively, whereas in the per patient perfusion analysis the respective percentages were 88, 64% for 2D and 90, 73% for RT3D. Regarding left anterior descending artery and right coronary system, there seems to be no statistical significant difference in terms of wall-motion and perfusion evaluation between the two modalities. CONCLUSIONS: Real-time 3D adenosine stress echocardiography is a feasible and valuable technique to evaluate myocardial wall motion and perfusion in patients with suspected CAD, despite existing problems concerning lower spatial and temporal resolution when compared with 2D echocardiography.

Cardiovascular Aging and Longevity: JACC State-of-the-Art Review.

Cardiovascular aging and longevity are interrelated through many pathophysiological mechanisms. Many factors that promote atherosclerotic cardiovascular disease are also implicated in the aging process and vice versa. Indeed, cardiometabolic disorders such as hyperglycemia, insulin resistance, dyslipidemia, and arterial hypertension share common pathophysiological mechanisms with aging and longevity. Moreover, genetic modulators of longevity have a significant impact on cardiovascular aging. The current knowledge of genetic, molecular, and biochemical pathways of aging may serve as a substrate to introduce interventions that might delay cardiovascular aging, thus approaching the goal of longevity. In the present review, the authors describe pathophysiological links between cardiovascular aging and longevity and translate these mechanisms into clinical data by reporting genetic, dietary, and environmental characteristics from long-living populations.

Triglycerides are related to left ventricular mass in hypertensive patients independently of other cardiometabolic risk factors: the effect of gender.

Given the inconsistent results on the prognostic significance of triglycerides (TGs), the purpose of the present study was to investigate the association of plasma TGs with left ventricular mass (LVM) in hypertensive patients. We studied 760 never treated, non diabetic, hypertensive patients. Τransthoracic echocardiography was performed and LVMI was calculated according to the Devereux formula, adjusted to body surface area. Triglycerides were associated with LVMI after adjustment for age, gender, systolic blood pressure (SBP), smoking and fasting glucose (b = 0.08, p = 0.009). This relationship remained significant even after adjustment for BMI, LDL-C and ApoB/ApoA1 ratio (b = 0.07, p = 0.04). Gender-stratified analysis indicated that TGs were related to LVMI in men (p = 0.001) but not in women (p = NS). In addition, TGs were related with LV hypertrophy (LVH) in men, increasing the odds by 7% to present LVMI over 115 g/m2 (OR = 1.07 per 10 mg/dl increase in TGs, p = 0.01). In conclusion, TGs are associated with LVMI in hypertensive patients, independently of other risk factors, including LDL-C. Given the prognostic significance of LVH, it might be suggested that TGs may serve as a useful marker for indentifying hypertensive patients at high risk. The gender discrepancy may suggest a possible gender-specific modulatory effect of TGs on LV structure.

Pharmacotherapeutic strategies for atrial fibrillation in pregnancy.

Introduction: Atrial fibrillation (AF) is rare during pregnancy but its incidence is expected to rise in parallel to increasing age of women in pregnancy and fraction of pregnant women with structural heart disease. Areas covered: The authors provide a review of the contemporary evidence on diagnostic work-up and optimal pharmacotherapeutic management of AF in pregnancy. The authors have performed a systematic search for relevant articles using MEDLINE, the COCHRANE LIBRARY, and ClinicalTrials.gov. Expert opinion: New-onset AF during pregnancy is usually an indication of underlying heart disease and should lead to hospital admission. Patients should be evaluated by an experienced cardiologist or an electrophysiologist. Direct cardioversion is highly effective and safe in pregnant women and should be prioritized over pharmacologic cardioversion with intravenous ibutilide or flecainide. Amiodarone should be avoided if possible. Digoxin and beta-blockers are the rate-control pharmaceutic agents with the widest experience of use. Catheter ablation during pregnancy should be considered in selected cases of atrial flutter refractory to medication and only performed using fluoroless techniques, preferably during the second trimester. Vitamin K antagonists (VKAs) can be used after the first trimester, while low molecular weight heparin should be accompanied by periodic evaluation of anti-Xa factor. Non-VKA oral anticoagulants should be avoided because of limited experience in pregnancy.

Effect of Ticagrelor Versus Clopidogrel on Aortic Stiffness in Patients With Coronary Artery Disease.

Background We compared the acute and midterm effect of ticagrelor versus clopidogrel on aortic stiffness. Methods and Results We studied 117 patients in a randomized, assessor-blinded, parallel-group trial. The acute effect of ticagrelor was studied in 58 patients randomized (1:1) to receive a loading dose of clopidogrel (600 mg) or ticagrelor (180 mg). Carotid-femoral pulse wave velocity (cf PWV ) was measured before, 3, and 24 hours after the loading dose. The midterm effect (30-day treatment period) was studied in 59 subjects who underwent percutaneous coronary intervention and were randomized to either clopidogrel (75 mg, OD) or ticagrelor (90 mg BID). cf PWV was measured before and at 30 days of treatment. Circulating markers of inflammation and endothelial function were measured at all study points. Repeated-measures analysis showed a significant main effect for treatment ( P=0.03), with the ticagrelor showing a reduction in cf PWV after treatment. cf PWV at 24 hours was significantly lower in the ticagrelor group compared with the clopidogrel group ( P=0.017) (maximal response reduction by 0.42±0.26 m/s). At 30 days, cf PWV decreased in the ticagrelor group, whereas there was no change with clopidogrel (-0.43±0.57 versus 0.12±0.14 m/s, P=0.004). There were no significant changes in both the acute and midterm study period in the pro-inflammatory and endothelial function parameters. Conclusions URL : https://www.clinicaltrials.gov . Unique identifier: NCT02071212. Ticagrelor decreases cf PWV for 24 hours after the loading dose and at 1 month post-percutaneous coronary intervention compared with clopidogrel. Considering that aortic stiffness is an independent predictor of cardiovascular events, this finding may have clinical implications regarding the beneficial effect of ticagrelor. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT02071212.

The effect of heart rate on wave reflections may be determined by the level of aortic stiffness: clinical and technical implications.

BACKGROUND: Augmentation Index (AIx) is related to cardiovascular diseases, risk, and mortality. AIx is associated with heart rate but the effect of aortic stiffness on this relationship has not been studied. The purpose of our study was to investigate the relationship between AIx and heart rate at different aortic stiffness levels. METHODS: The study consisted of 425 normotensive and untreated hypertensive subjects. Wave reflections and pulse-wave velocity (PWV) were determined by the Sphygmocor and the Complior systems, respectively. RESULTS: AIx was independently associated with heart rate, age, gender, height, mean blood pressure (BP) and the effective reflection site distance (ERD). The population was divided into three groups of those with different PWV levels (tertiles). The regression lines for AIx with heart rate differed significantly between the 3rd and the other two tertiles of PWV (P = 0.039 for slopes and P = 0.002 for intercepts). This difference remained significant even after adjustment for age, gender, height, mean BP, and distance of wave reflections. CONCLUSIONS: A significantly stronger correlation of AIx with heart rate was observed in subjects with higher levels of aortic stiffness as compared to those with lower levels; namely, the same increase in the heart rate between subjects, induced a greater decrease in the AIx at higher compared to lower PWV levels. The correction of AIx for heart rate should be reconsidered based on the aortic stiffness level. This finding has implications for interventional studies that aim to improve central hemodynamics but simultaneously affect heart rate. Further studies that show acute modifications of heart rate at different arterial stiffness levels are required to support these findings.

Regression of organ damage following renal denervation in resistant hypertension: a meta-analysis.

AIMS: Prospective observational studies have suggested that renal denervation (RDN) is associated with target organ damage (TOD) regression. Our aim is to review and meta-analyze the available evidence for the effect of RDN on TOD. METHODS: We searched literature for studies with eligible content and performed random-effect meta-analyses for the following outcomes: left ventricular mass index (LVMI), left atrial volume index (LAVI), E to A wave velocities of trans-mitral inflow (E/A) and E wave velocity to Em velocity from tissue Doppler imaging (E/Em), central augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV). RESULTS: Seventeen studies (n = 698 patients) were incorporated in the present meta-analysis. RDN led to a regression of LVMI by 14.17 g/m (95% CI -18.33 to -10.01, P < 0.001) and by 4.75 g/m (95% CI -7.83 to -1.67, P = 0.003) for echocardiography and cardiac magnetic resonance, respectively. The pooled effect of RDN to E/A was not significant [0.04 (95% CI -0.03 to 0.12, P = 0.252)], whereas a decline of E/Em [-0.73 (95% CI -1.38 to -0.08, P = 0.03)] was observed. The pooled effect to LAVI [-1.67 ml/m (95% CI -4.60 to 1.27, P = 0.266)] reached statistical significance only in sensitivity analysis. RDN had beneficial effects in both AIx [-7.05 (95% CI -9.12 to -4.98, P < 0.001)] and PWV [1.54 m/s (95% CI -2.16 to -0.92, P < 0.001)]. Metaregression analysis revealed an independent effect of RDN on TOD regarding baseline blood pressure and blood pressure reduction. CONCLUSION: Catheter-based RDN can favorably affect TOD.

Relationship of fibrinogen with arterial stiffness and wave reflections.

INTRODUCTION: Increased levels of fibrinogen have been related to target organ damage and cardiovascular outcomes. Arterial elastic properties are important determinants of cardiovascular performance and predictors of the corresponding risk. This study investigated whether the fibrinogen level is associated with arterial stiffness and wave reflections. METHODS: We studied 229 consecutive, non-diabetic patients with uncomplicated, never-treated essential hypertension (mean age 51 years, 149 men) and an age-matched control group of 159 normotensive individuals (mean age 50 years, 83 men). Carotid-femoral and carotid-radial pulse wave velocity (PWVc-f and PWVc-r) were measured as indices of elastic-type, aortic stiffness and muscular type, medium-sized arterial stiffness, respectively. The heart rate-corrected augmentation index (AIx75) was estimated as a composite marker of wave reflections and arterial stiffness. Plasma fibrinogen was measured using immunonephelometry. RESULTS: The fibrinogen level and arterial function indices (PWVc-f, PWVc-r, AIx75) were significantly higher in hypertensive patients than controls. In the whole population, fibrinogen level correlated with PWVc-f and AIx75 in univariable analysis, but not with PWVc-r. In multivariable analysis, an independent association was established between fibrinogen level and PWVc-f after adjusting for age, sex, mean pressure, heart rate, height, body mass index, smoking status, and total cholesterol. In contrast, no significant relationship was observed between fibrinogen and AIx75 after adjusting for confounders. CONCLUSION: The plasma fibrinogen level is independently associated with aortic stiffening. This finding underlines the important role of fibrinogen as a marker of arterial damage, and implies a possible contribution of this compound to the pathophysiology of cardiovascular disease.

Nocturnal blood pressure fall and metabolic syndrome score in hypertensive patients.

BACKGROUND: Data relating dipping status to metabolic syndrome (MS) scores are not available. The purpose of this study is to investigate any possible association of different dipping patterns to MS scores in untreated patients with essential hypertension. METHODS: The study included 6256 consecutive, treatment-naive patients with essential hypertension who attended our outpatient clinics. All underwent repeated office blood pressure measurements, 24-h ambulatory blood pressure monitoring, and full clinical and laboratory evaluation. The diagnosis of MS was made according to the Adult Treatment Panel III criteria and patients were classified into five groups: group I (hypertension), group II (hypertension+any one component), group III (hypertension+any two components), group IV (hypertension+any three components), and group V (all five components). Dipping pattern was defined as 'dippers' with nocturnal systolic blood pressure (NSBP) falling >or=10 but <20%, 'nondippers' with NSBP falling >or=0% but <10%, 'extreme dippers' with NSBP falling >or=20%, and 'reverse dippers' with NSBP increasing. RESULTS: Hypertensive patients with MS (n=2573) had higher clinical and ambulatory blood pressure values (P<0.001), whereas the dominant dipping pattern in the non-MS group was nondippers (47.6%), and in the MS group, extreme dippers (37.8%). Furthermore, a considerable decrease in the prevalence of dippers was noticed with the increasing number of MS components (21.1 vs. 19.2 vs. 14.5 vs. 8.4 vs. 7.2%, P<0.001). In contrast, a significant rise in the prevalence of reverse dippers was observed with the increasing number of MS components (7.4 vs. 10.1 vs. 14.9 vs. 20.4 vs. 31.2%, P<0.001). CONCLUSIONS: It seems that hypertensive patients have an increased prevalence of abnormal dipping patterns as the number of MS components rises.

Beneficial effects of angiotensin II type 1 receptor blocker antihypertensive treatment on inflammation indices: the effect of smoking.

The effect of long-term angiotensin II type 1 receptor blocker (ARB) therapy on inflammation indices has not been fully investigated in a hypertensive population. The authors evaluated 323 consecutive nondiabetic patients (mean age, 57 years; 176 men; 92 smokers) with high renin activity and uncomplicated essential hypertension whose blood pressure levels normalized (from 163.9/100.7 mm Hg to 131.6/82.8 mm Hg) after 4 weeks of ARB or ARB/diuretic treatment. All patients underwent full laboratory evaluation (routine examination of blood and urine, liver, kidney, thyroid function, and lipid and glucose profiles), including measurement of high-sensitivity C-reactive protein and serum amyloid A levels, at drug-free baseline, which was repeated after 6 months of ARB or ARB/diuretic treatment. A significant (P<.001) overall decrease was noted in both high-sensitivity C-reactive protein (-0.41+/-1.56 mg/dL) and serum amyloid A (-0.62+/-2.03 mg/dL), but a smaller decrease in high-sensitivity C-reactive protein and serum amyloid A change was seen in the smoker subgroup compared with nonsmokers (P<.05), indicating that the ARB or ARB/diuretic anti-inflammatory effect may be adversely affected by smoking status.

Relationship between low-grade inflammation and arterial stiffness in patients with essential hypertension.

BACKGROUND: Arterial stiffness is an independent cardiovascular risk factor in hypertensive individuals. Inflammation is associated with increased arterial stiffness and is implicated in the pathogenesis of hypertension. OBJECTIVES: To examine whether low-grade inflammation contributes to arterial stiffness and wave reflections independently of blood pressure, in patients with essential hypertension and in controls. METHODS: We studied 235 consecutive patients with uncomplicated, never-treated essential hypertension and 103 sex- and age-matched controls. The level of inflammation was evaluated with high-sensitivity C-reactive protein (hsCRP) and serum amyloid A (SAA). Arterial stiffness was assessed with carotid-femoral (c-f) and carotid-radial (c-r) pulse wave velocity (PWV), and wave reflections with augmentation index (AIx). RESULTS: In the hypertensive group, in multiple regression analysis, both PWVc-f and PWVc-r were independently correlated with log hsCRP (beta = 0.56, P = 0.006 and beta = 0.45, P = 0.016, respectively), whereas no correlation was found between PWV and log SAA (P = NS). No significant correlation was observed between heart-rate-corrected AIx and log hsCRP (P = NS) and log SAA (P = 0.07) in the same group. Similarly, in the control group, an independent association was observed between PWVc-f and PWVc-r with log hsCRP (beta = 0.68, P = 0.05 and beta = 0.74, P = 0.05 respectively), but not with log SAA (P = NS). Furthermore, no significant association was shown between heart-rate-corrected AIx and log hsCRP or log SAA (P = NS) in the control group. CONCLUSIONS: In hypertensive individuals, hsCRP is related to PWV, a direct marker of arterial stiffness, but not to AIx, a measure of wave reflections. Whether inflammation might act as a pathogenetic or modulating factor in arterial stiffening in chronic hypertension has to be confirmed.

Office blood pressure is a predictor of aortic elastic properties and urinary protein excretion in subjects with white coat hypertension.

BACKGROUND: White coat hypertension (WCH) is related to target organ damage and increased cardiovascular risk. Arterial elastic properties and urinary protein excretion are determinants of cardiovascular performance and predictors of outcomes. We investigated whether office blood pressure (BP) is a better determinant of arterial and renal function than the ambulatory BP in WCH patients. METHODS: We studied 440 consecutive untreated non-diabetic patients with WCH (office BP >140/90 mmHg, mean daytime ambulatory BP <135/85 mmHg). Arterial function was evaluated with carotid-femoral pulse wave velocity (cfPWV), an index of aortic stiffness, and aortic augmentation index (AIx), a composite marker of aortic stiffness and wave reflections. In 24-hour urine, albumin excretion and albumin/creatinine ratio (ACR) were measured as markers of glomerular function and urinary α1-microglobulin was measured as a marker of renal tubular function. RESULTS: In univariate analysis, office systolic BP correlated significantly with cfPWV (r=0.245, P<0.001), AIx (r=0.31, P<0.001), albumin (r=0.134, P=0.005), ACR (r=0.199, P<0.001) and α1-microglobulin (r=0.118, P=0.013). In contrast, mean ambulatory systolic BP did not correlate with arterial function or urinary proteins (all P>0.5). Hierarchical multilevel linear regression analysis showed that office systolic BP is an independent determinant of cfPWV (P=0.050), AIx (P=0.029), albumin (P=0.002) and ACR (P=0.001) and has a borderline association with α1-microglobulin (P=0.088). CONCLUSIONS: In non-diabetic WCH individuals, office systolic BP is an independent predictor of aortic elastic properties and urinary protein excretion, whereas ambulatory BP is not. This finding suggests that office BP may be a marker of cardiovascular risk in subjects with WCH.

Inverse association of total testosterone with central haemodynamics and left ventricular mass in hypertensive men.

BACKGROUND: There is evidence for inverse association between endogenous testosterone and blood pressure. Furthermore, low plasma testosterone is associated with increased risk of major cardiovascular events in middle-aged hypertensive men. Central (aortic) blood pressures determine left ventricular hypertrophy and predict cardiovascular mortality. The aim of the present study was to assess the relationship of total testosterone (TT) with central haemodynamics and left ventricular mass in hypertensive men. METHODS: We investigated 134 non-diabetic, middle-aged, hypertensive men and 60 age-matched normotensive males. All participants were subject to measurement of aortic systolic (aoSBP) and pulse pressure (aoPP) by pulse wave analysis using the SphygmoCor device. Wave reflections were assessed by the measurement of heart rate corrected augmentation index (AIx75). Echocardiography was performed in all individuals and left ventricular mass (LVM) was calculated using the Devereux's formula. Plasma TT was measured by enzyme immunoassay. RESULTS: In hypertensive men, univariate analysis showed an inverse, significant correlation between TT and aoSBP (r = -20, p = 0.02), aoPP (r = -0.21, p = 0.01), AIx75 (r = -0.22, p = 0.01) and LVM (r = -0.19, p = 0.008). Multivariate regression analysis demonstrated an independent inverse association of TT with aoPP (b = -0.21, p = 0.02), AIx75 (b = -0.19, p = 0.03) and LVM (b = -0.28, p = 0.005) after adjustment for age, BMI, smoking, total cholesterol, triglycerides, fasting glucose, mean arterial pressure, antihypertensive treatment and statin use. Independent associations were retained even after inclusion of normotensive subjects in the analysis. CONCLUSIONS: In hypertensive men, TT is independently and inversely associated with central pulse pressure, wave reflections and left ventricular mass. Considering the adverse prognostic role of central blood pressures and LV hypertrophy on cardiovascular outcomes in hypertensive patients, the present findings might explain part of the increased cardiovascular risk associated with low testosterone. Whether measurement of central haemodynamics may improve risk stratification in hypertensive men with low testosterone warrants further investigation.

Inflammation and Arterial Hypertension: From Pathophysiological Links to Risk Prediction.

Over the last years, ample data have demonstrated the pivotal role of low-grade inflammation in the pathophysiology of atherosclerosis and cardiovascular disease. It is well established that inflammatory activation, serving either as a substrate, in the chronic phase of atherosclerotic disease, or as a trigger, in the acute phase, increases cardiovascular events. Considering hypertension, the inflammatory process is implicated in its pathophysiology through a bidirectional relationship since arterial hypertension may enhance inflammation and vice versa. Inflammatory biomarkers such as high-sensitivity C-reactive protein, have shown predictive value for both the incidence of hypertension and the clinical outcomes in hypertensive patients. In the present review, data on the association between arterial hypertension and low-grade inflammation will be reported and potential pathophysiological pathways and clinical implications underlying this association will be discussed.

Association between pneumococcal vaccination and cardiovascular outcomes: a systematic review and meta-analysis of cohort studies.

AIMS: Streptococcus pneumoniae is the most common cause of community-acquired pneumonia (CAP) and CAP-related mortality in adults. Pneumococcal vaccination (PV) could protect subjects from cardiovascular events by reducing pneumonia severity or even preventing it. We sought to determine the ability of PV to protect from the risk of cardiovascular events. METHODS AND RESULTS: A comprehensive search of electronic databases was conducted up to March 2014. Cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CI) were included. Eleven studies were included (332,267 participants, mean follow-up 20.1 months). The pooled RRs for cardiovascular events and cardiovascular mortality were 0.86 (95% CI: 0.76-0.97) and 0.92 (95% CI: 0.86-0.98; fixed-effects), respectively, for subjects with PV versus without PV. Protective ability was more prominent in high cardiovascular risk populations and with older age. The protective role of PV was attenuated after 1 year (RR: 0.72; 95% CI: 0.59-0.88 vs RR: 1.03; 95% CI: 0.93-1.14; p = 0.002, for follow-up >1 year vs ≤1 year, respectively). It also increased as the presence of cardiovascular and pulmonary disease increased. Regarding myocardial infarction (MI) and cerebrovascular events, the protective role of PV was statistically significant only in the elderly (RR: 0.90; 95% CI: 0.817-0.999; fixed-effects and RR: 0.86; 95% CI: 0.75-0.99, respectively). CONCLUSION: PV is associated with decreased risk of cardiovascular events and mortality. This protective effect increases at older age and in high cardiovascular risk subjects and decreases as the time elapses from PV. PV decreases the risk of MI and cerebrovascular events in the elderly.