Konstantinos Aznaouridis

Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis.

OBJECTIVES The purpose of this study was to calculate robust quantitative estimates of the predictive value of aortic pulse wave velocity (PWV) for future cardiovascular (CV) events and all-cause mortality by meta-analyses of longitudinal studies. BACKGROUND Arterial stiffness is increasingly recognized as a surrogate end point for CV disease. METHODS We performed a meta-analysis of 17 longitudinal studies that evaluated aortic PWV and followed up 15,877 subjects for a mean of 7.7 years. RESULTS The pooled relative risk (RR) of clinical events increased in a stepwise, linear-like fashion from the first to the third tertile of aortic PWV. The pooled RRs of total CV events, CV mortality, and all-cause mortality were 2.26 (95% confidence interval: 1.89 to 2.70, 14 studies), 2.02 (95% confidence interval: 1.68 to 2.42, 10 studies), and 1.90 (95% confidence interval: 1.61 to 2.24, 11 studies), respectively, for high versus low aortic PWV subjects. For total CV events and CV mortality, the RR was significantly higher in high baseline risk groups (coronary artery disease, renal disease, hypertension) compared with low-risk subjects (general population). An increase in aortic PWV by 1 m/s corresponded to an age-, sex-, and risk factor-adjusted risk increase of 14%, 15%, and 15% in total CV events, CV mortality, and all-cause mortality, respectively. An increase in aortic PWV by 1 SD was associated with respective increases of 47%, 47%, and 42%. CONCLUSIONS Aortic stiffness expressed as aortic PWV is a strong predictor of future CV events and all-cause mortality. The predictive ability of arterial stiffness is higher in subjects with a higher baseline CV risk.

Quarterly Focus Issue: Prevention/OutcomeClinical Research: Cardiovascular RiskPrediction of Cardiovascular Events and All-Cause Mortality With Arterial Stiffness: A Systematic Review and Meta-Analysis

OBJECTIVES The purpose of this study was to calculate robust quantitative estimates of the predictive value of aortic pulse wave velocity (PWV) for future cardiovascular (CV) events and all-cause mortality by meta-analyses of longitudinal studies. BACKGROUND Arterial stiffness is increasingly recognized as a surrogate end point for CV disease. METHODS We performed a meta-analysis of 17 longitudinal studies that evaluated aortic PWV and followed up 15,877 subjects for a mean of 7.7 years. RESULTS The pooled relative risk (RR) of clinical events increased in a stepwise, linear-like fashion from the first to the third tertile of aortic PWV. The pooled RRs of total CV events, CV mortality, and all-cause mortality were 2.26 (95% confidence interval: 1.89 to 2.70, 14 studies), 2.02 (95% confidence interval: 1.68 to 2.42, 10 studies), and 1.90 (95% confidence interval: 1.61 to 2.24, 11 studies), respectively, for high versus low aortic PWV subjects. For total CV events and CV mortality, the RR was significantly higher in high baseline risk groups (coronary artery disease, renal disease, hypertension) compared with low-risk subjects (general population). An increase in aortic PWV by 1 m/s corresponded to an age-, sex-, and risk factor-adjusted risk increase of 14%, 15%, and 15% in total CV events, CV mortality, and all-cause mortality, respectively. An increase in aortic PWV by 1 SD was associated with respective increases of 47%, 47%, and 42%. CONCLUSIONS Aortic stiffness expressed as aortic PWV is a strong predictor of future CV events and all-cause mortality. The predictive ability of arterial stiffness is higher in subjects with a higher baseline CV risk.

Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis.

AIMS To calculate robust quantitative estimates on the predictive value of central pressures and derived central haemodynamic indices for cardiovascular (CV) outcomes and all-cause mortality by meta-analysis of longitudinal studies. METHODS AND RESULTS We meta-analysed 11 longitudinal studies that had employed measures of central haemodynamics and had followed 5648 subjects for a mean follow-up of 45 months. The age- and risk-factor-adjusted pooled relative risk (RR) of total CV events was 1.088 (95% CI 1.040-1.139) for a 10 mmHg increase of central systolic pressure, 1.137 (95% CI 1.063-1.215) for a 10 mmHg increase of central pulse pressure (PP), and 1.318 (95% CI 1.093-1.588) for a 10% absolute increase of central augmentation index (AIx). Furthermore, we found that a 10% increase of central AIx was associated with a RR of 1.384 (95% CI 1.192-1.606) for all-cause mortality. When compared with brachial PP, central PP was associated with marginally but not significantly higher RR of clinical events (P = 0.057). CONCLUSION Central haemodynamic indexes are independent predictors of future CV events and all-cause mortality. Augmentation index predicts clinical events independently of peripheral pressures, while central PP has a marginally but not significantly (P = 0.057) better predictive ability when compared with peripheral PP.

Acute Systemic Inflammation Increases Arterial Stiffness and Decreases Wave Reflections in Healthy Individuals

Background— Aortic stiffness is a marker of cardiovascular disease and an independent predictor of cardiovascular risk. Although an association between inflammatory markers and increased arterial stiffness has been suggested, the causative relationship between inflammation and arterial stiffness has not been investigated. Methods and Results— One hundred healthy individuals were studied according to a randomized, double-blind, sham procedure-controlled design. Each substudy consisted of 2 treatment arms, 1 with Salmonella typhi vaccination and 1 with sham vaccination. Vaccination produced a significant (P<0.01) increase in pulse wave velocity (at 8 hours by 0.43 m/s), denoting an increase in aortic stiffness. Wave reflections were reduced significantly (P<0.01) by vaccination (decrease in augmentation index of 5.0% at 8 hours and 2.5% at 32 hours) as a result of peripheral vasodilatation. These effects were associated with significant increases in inflammatory markers such as high-sensitivity C-reactive protein (P<0.001), high-sensitivity interleukin-6 (P<0.001), and matrix metalloproteinase-9 (P<0.01). With aspirin pretreatment (1200 mg PO), neither pulse wave velocity nor augmentation index changed significantly after vaccination (increase of 0.11 m/s and 0.4%, respectively; P=NS for both). Conclusions— This is the first study to show through a cause-and-effect relationship that acute systemic inflammation leads to deterioration of large-artery stiffness and to a decrease in wave reflections. These findings have important implications, given the importance of aortic stiffness for cardiovascular function and risk and the potential of therapeutic interventions with antiinflammatory properties.

Prediction of Cardiovascular Events and All-Cause Mortality With Brachial-Ankle Elasticity Index A Systematic Review and Meta-Analysis

Brachial-ankle elasticity index (baEI; also known as brachial-ankle pulse wave velocity) has been proposed as a surrogate end point for cardiovascular disease. We performed a meta-analysis of longitudinal cohort studies for determining the ability of baEI to predict risk of cardiovascular events and all-cause mortality and dissecting factors influencing this predictive ability. Multiple online databases, reference lists from retrieved articles, and abstracts from international cardiovascular conventions were searched until April 2012. Longitudinal cohort studies that reported associations of baEI with clinical risk were included. Of the 18 studies included (8169 participants; mean follow-up, 3.6 years), 15 reported results on total cardiovascular events (5544 individuals), 7 on cardiovascular mortality (2274 individuals), and 9 on all-cause mortality (5097 individuals). The pooled relative risks for total cardiovascular events, cardiovascular mortality, and all-cause mortality were 2.95 (95% CI, 1.63–5.33), 5.36 (95% CI, 2.17–13.27), and 2.45 (95% CI, 1.56–3.86), respectively, for subjects with high versus low baEI (all P<0.001). An increase in baEI by 1 m/s corresponded with an increase of 12%, 13%, and 6% in total cardiovascular events, cardiovascular mortality, and all-cause mortality, respectively. We conclude that baEI is associated with increased risk of total cardiovascular events and all-cause mortality. Issues such as expansion of data to non-Asian populations, validation of path length estimation, determination of reference values, and prospective comparison with carotid-femoral pulse wave velocity remain to be resolved.

Prediction of Cardiovascular Events and All-Cause Mortality With Erectile Dysfunction A Systematic Review and Meta-Analysis of Cohort Studies

Background— Erectile dysfunction (ED) carries an independent risk for cardiovascular (CV) events. We conducted a meta-analysis of all longitudinal studies for determining the ability of ED to predict risk of clinical events and to dissect factors influencing this ability. Methods and Results— We conducted a comprehensive search of electronic databases through July 2012. Longitudinal studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) were included. Of the 14 studies included (92 757 participants; mean follow-up, 6.1 years; 16 articles), 13 (14 articles) reported results on total CV events (91 831 individuals), 4 on CV mortality (34 761 individuals), 4 on myocardial infarction (35 523 individuals), 6 on cerebrovascular events (27 689 individuals), and 5 on all-cause mortality (17 869 individuals). The pooled RRs for the above-mentioned end points were 1.44 (95% CI, 1.27–1.63), 1.19 (95% CI, 0.97–1.46), 1.62 (95% CI, 1.34–1.96), 1.39 (95% CI, 1.23–1.57), and 1.25 (95% CI, 1.12–1.39), respectively, for men with versus without ED. The RR was higher in intermediate- compared with high- or low-CV-risk populations and with younger age. The RR for studies that diagnosed ED with the use of a questionnaire compared with a single question was higher (RR, 1.61; 95% CI, 1.38–1.86 versus RR, 1.27; 95% CI, 1.18–1.37, respectively; P=0.006). Conclusions— ED is associated with increased risk of CV events and all-cause mortality. RR is higher at younger ages, in intermediate-risk groups, and when a questionnaire is used instead of a single question.

Effect of coffee on endothelial function in healthy subjects: the role of caffeine

Coffee is one of the most widely used pharmacologically active beverages. The present study was designed to evaluate the acute effect of coffee ingestion on endothelial function in healthy individuals, and the potential role of caffeine. We studied 17 healthy young adults (28.9+/-3.0 years old; nine men), who were regular non-heavy coffee drinkers. The endothelial performance was estimated by endothelium-dependent FMD (flow-mediated dilatation) of the brachial artery before and 30, 60, 90 and 120 min after ingestion of a cup of caffeinated coffee (80 mg of caffeine) or the corresponding decaffeinated beverage (< 2 mg of caffeine) in two separate sessions, following a randomized single-blind cross-over design. There was no difference in baseline FMD values between the two sessions [7.78 compared with 7.07% after caffeinated and decaffeinated coffee respectively; P = NS (not significant)]. Caffeinated coffee led to a decline of FMD (7.78, 2.86, 2.12, 4.44 and 4.57% at baseline, 30, 60, 90 and 120 min respectively; P < 0.001). This adverse effect was focused at 30 (P = 0.004) and 60 min (P < 0.001). No significant effect on FMD was found with the decaffeinated coffee session (7.07, 6.24, 5.21, 7.41 and 5.20%; P = NS). The composite effect of the type of coffee consumed over time on FMD was significantly different (P = 0.021). In conclusion, coffee exerts an acute unfavourable effect on the endothelial function in healthy adults, lasting for at least 1 h after intake. This effect might be attributed to caffeine, given that decaffeinated coffee was not associated with any change in the endothelial performance.

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 (β = 0.56, P = 0.006 and β = 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 (β = 0.68, P = 0.05 and β = 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.

Increased arterial stiffness and impaired endothelial function in nonalcoholic Fatty liver disease: a pilot study.

BACKGROUND Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease both in the general and pediatric population and has been associated with increased cardiovascular risk. Arterial function and early atherosclerotic changes are markers of cardiovascular disease and independent predictors of the corresponding risk. Through a global approach, we investigated the relationships between NAFLD and functional arterial changes and early atherosclerosis. METHODS A total of 23 consecutive patients (mean age 55 ± 14 years, 11 males) with biopsy evidence of NAFLD and 28 control subjects matched for age, gender, body mass index, and other cardiovascular risk factors participated in the study. RESULTS Compared to controls, NAFLD subjects had significantly higher carotid-femoral pulse wave velocity (PWV; 8.2 ± 1.3 m/s vs. 6.9 ± 1.3 m/s, P = 0.001), higher carotid intima-media thickness (IMT; 0.79 ± 0.18 mm vs. 0.67 ± 0.13 mm, P = 0.01), and reduced flow-mediated dilatation (FMD; 1.92 ± 2.11% vs. 4.8 ± 2.43%, P < 0.001). In multivariable analysis, presence of NAFLD was an independent determinant of both PWV and FMD, whereas leptin was an independent determinant of PWV (B = 0.036, P < 0.05), and adiponectin was independently associated with FMD (B = 0.104, P < 0.05). In addition, histological activity of liver disease expressed by the global Brunt Grade was associated independently with FMD (B = -1.054, P < 0.05). CONCLUSIONS NAFLD is associated with arterial stiffness and endothelial dysfunction. Given the important independent prognostic role of these arterial indexes, these findings have important implications for increased cardiovascular risk in patients with NAFLD.

Clinical appraisal of arterial stiffness: the Argonauts in front of the Golden Fleece

Interest in evaluating arterial elastic properties has grown in parallel with the widespread availability of non-invasive methods for assessing arterial stiffness. A clinically useful diagnostic index must be pathophysiologically relevant, must be readily measurable, and must indicate the severity of the disease and predict the corresponding risk. Interventional modification of this index must parallel disease regression and benefit prognosis. The current evidence for the clinical value of estimating arterial stiffness (mainly of large, elastic-type arteries, such as the aorta and the carotids) in the contemporary era of cardiovascular medicine is reviewed.