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) [...].

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.

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.

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.

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.

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.

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.

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.

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.

Testosterone deficiency: a determinant of aortic stiffness in men.

OBJECTIVE: Low testosterone levels and increased aortic stiffness are predictors of cardiovascular events. The influence of androgen level on the age- and blood pressure-related increase in aortic stiffness is unknown. METHODS: From January 2007 to June 2011 we enrolled 455 consecutive men with no evidence of cardiovascular disease from a large cohort followed in our Department for arterial function studies. Their total testosterone (TT) levels were measured and carotid-femoral pulse wave velocity (PWVc-f) was measured as an index of aortic stiffness. RESULTS: In multivariable analysis, PWVc-f values were inversely correlated to TT after adjustment for confounders (ß = -0.365, P < 0.001). In younger age categories (<50 yrs and 50-59 yrs), patients with testosterone deficiency (TD) had higher blood pressure-adjusted PWVc-f (P < 0.001 and P = 0.005, respectively) compared to subjects with normal TT, indicating an "aging effect" of 10 years, whereas in older age categories such a difference was not observed. Furthermore, in men with a higher mean pressure (102-108 mmHg and >108 mmHg), patients with TD had higher age-adjusted PWVc-f (P < 0.001) compared to subjects with normal TT, indicating a synergistic unfavorable effect of testosterone deficiency and blood pressure on aortic stiffness. CONCLUSIONS: TT levels are independently associated with aortic stiffening. The effect of low testosterone concentration on aortic stiffness is more prominent in young men and in subjects with higher blood pressure levels. These findings identify testosterone as a marker of arterial damage with special emphasis on young and hypertensive individuals and support its role as predictor of events.

Macro- and microvascular alterations in patients with metabolic syndrome: sugar makes the difference.

Metabolic syndrome (MS) is associated with adverse cardiovascular events, although its prognostic significance over and beyond the clustering risk factors is controversial. Moreover, there are no data on the possible differentiation of target organ damage among patients with MS according to the grade of its distinct components. We studied 500 hypertensive patients with MS and we assessed vascular damage according to glucose metabolic status (1, normal glucose metabolism (NG); 2, impaired fasting glucose (IFG); 3, impaired glucose tolerance (IGT); and 4, diabetes mellitus II (DM II)). Macrovascular damage was assessed with arterial stiffness by measuring carotid-femoral pulse wave velocity (PWV). Microvascular damage was assessed with albumin excretion by estimating the albumin-creatinine ratio (ACR). There was a significant progressive increase in PWV from group 1 to group 4 (from 7.97 to 8.83 to 8.94 to 10.27 m s(-1), respectively) that remained statistically significant even after adjustment for several confounders (P<0.001). Similar trends were also observed for ACR (from 27.44 to 29.94 to 36.26 to 73.07 mg g(-1), P<0.001). In multiple regression analysis, both PWV and ACR were independently related to glucose metabolic status (P=0.001 and P<0.001, respectively). Vascular alterations among patients with MS differ according to the grade of glucose dysregulation. Considering the adverse prognostic role of arterial stiffness and microalbuminuria, it might be argued that the cardiovascular risk is not homogeneously distributed among patients with MS but is largely determined by glucose metabolic status.