Predictor Of Future Cardiovascular Events Research Articles

Aortic calcifications and arterial stiffness as predictors of cardiovascular events in incident renal transplant recipients

Renal transplant recipients have an increased risk of cardiovascular (CV) disease. Arterial stiffness (AS) and aortic calcifications (ACs) are well-known CV risk factors in patients with chronic kidney disease. We aimed to determine the prognostic value of AS and AC in incident renal transplant recipients (RTRs). We conducted a prospective study in 253 single RTR. AC were scored by means of lumbar X-ray. Carotid-femoral pulse wave velocity (PWV) was assessed in a subgroup of 115 patients. AC were present in 61% of patients. After a mean follow-up of 36months, 32 CV events occurred in the overall group and 13 events in the PWV subgroup. When we accounted for age, gender, and CV history, AC score (HR, hazard ratio 1.09 per 1 unit increase; 95% CI 1.02-1.17) and PWV (HR 1.45 per 1m/s; 95% CI 1.16-1.8) remained an independent predictor of CV events in Cox-regression analyses. Using receiver operating characteristics, the area under the curve for predicting CV events amounted to 0.80 and 0.72 for sum AC and PWV, respectively. Both AS and AC are strong predictors of future CV events in an incident RTR population. These vascular assessments are readily available and easy to perform, making them ideal tools for further risk stratification. (ClinicalTrials.gov number: NCT00547040).

Insulin resistance negatively affects long-term outcome in non-diabetic patients with coronary artery disease after therapies to reduce atherosclerotic risk factors

BackgroundInsulin resistance (IR) is a predictor of cardiovascular (CV) events even before the onset of diabetes. However, it is unclear whether changes in IR after a reduction of atherosclerotic burden may affect long-term outcome in patients with coronary artery disease (CAD). This study examined whether changes in IR after therapy to reduce atherosclerotic risk factors provides prognostic information on future CV events in non-diabetic patients with CAD. Methods and resultsThis study enrolled 175 non-diabetic patients with newly diagnosed CAD and IR. IR was defined as the homeostasis model assessment of IR (HOMA-IR)≧2.5. Evaluation of HOMA-IR was repeated at entry (1st test) and 6 months after individualized, optimized therapy including medications and lifestyle changes (2nd test). After the 2nd test, all patients were prospectively followed-up for 3 years or until the occurrence of one of the following events: CV death, nonfatal myocardial infarction, unstable angina requiring coronary revascularization, or ischemic stroke. IR was improved (HOMA-IR<2.5) after 6 months in 71 (41%) patients, whereas IR persisted in 104 (59%) patients. During the follow-up period, events occurred in 21 (20%) of the 104 patients with persistent IR and 3 (4%) of the 71 patients with improved IR (p<0.01). In multivariate stepwise Cox proportional hazards analysis, persistent IR was an independent predictor of future CV events (HR 4.8, 95% CI 1.4–11.2, p<0.01). ConclusionsThe presence of IR despite optimized therapies to reduce atherosclerotic risk factors represents an adverse outcome predictor in non-diabetic patients with CAD.

Evaluation of left atrial function using two-dimensional speckle tracking echocardiography in end-stage renal disease patients with preserved left ventricular ejection fraction

Left atrial (LA) deformation analysis by two-dimensional speckle tracking echocardiography (2D-STE) has recently been proposed as an alternative approach for estimating left ventricular (LV) filling pressure and dysfunction. To assess the LA myocardial function using 2D-STE in end-stage renal disease (ESRD) patients with preserved LV ejection fraction (PLVEF) and to evaluate the relationship of the obtained results with echocardiographically estimated pulmonary capillary wedge pressure (ePCWP). Eighty-five ESRD patients and 60 healthy individuals were enrolled in the study. Images of the LA were acquired from apical two- and four-chamber views. The LA volumes (LAV) were calculated using the biplane area-length method. The LA volume indices (LAVI) were calculated by dividing the LA volumes by the body surface area. The LA strain (%) (LAS) parameters (systolic [LA(S-S)], early diastolic [LA(S-E)], late diastolic [LA(S-A)] during atrial contraction) were assessed, and the ePCWP was calculated according to the following formula: ePCWP = 1.25(E/E') + 1.9. LA stiffness was calculated non-invasively and based on the ratio of E/E' to LAS-S. In patients with ESRD, the LA(S-S) (32.22 ± 7.64% vs. 57.93 ± 8.71%; p < 0.001), LA(S-E) (-15.86 ± 5.7% vs. -33.37 ± 7.71%; p < 0.001), and the LA(S-A) (-15.41 ± 4.16% vs. -24.57 ± 4.68%; p < 0.001) values were observed to be lower than the healthy group; while the LA stiffness (0.4 ± 0.19 vs. 0.17 ± 0.05; p < 0.001) value was higher. When the patients with ESRD were divided into two groups as those with a maximum LAVI value over 31.34 mL/m² and those with a maximum LAVI below this value, the LA(S-S) (30.36 ± 8.32% vs. 34.11 ± 6.43%; p = 0.023) and the LA(S-E) (-14.97 ± 5.88% vs. -16.76 ± 5.42%; p = 0.039) values were lower in the group with a LAVI value over 31.34 mL/m²; while the LA(S-A) (-16.06 ± 4.44% vs. -14.75 ± 3.8%; p < 0.001) and LA stiffness (0.4 ± 0.19 vs. 0.17 ± 0.05; p < 0.001) values were higher. An association was observed between the ePCWP and LA(S-S) (p < 0.001), LAS-E (p = 0.01), LA(S-A) (p < 0.001), and LA stiffness (p < 0.001) values. The results of our study have demonstrated that LA myocardial function assessed using the 2D-STE method is associated with the ePCWP, which is an echocardiographically calculated marker of LV dysfunction. The LA deformation parameters may be used as echocardiographic findings to predict the LV dysfunction in ESRD patients with PLVEF. Further studies are needed to determine the independent prognostic power of the atrial strain measurement as a predictor of future cardiovascular events in ESRD patients.

Evaluation of Ankle-Brachial Pressure Index and Carotid Intima Media Thickness by Doppler Ultrasound in type two Diabetics.

Background: Atherosclerosis causes thickening of the artery walls. The intima-media thickness (IMT) of the common carotid artery (CCA) is widely used as an early indicator of the development of coronary artery disease, atherosclerosis, and independently cardiovascular disease (CVD). Diabetes increased the risk of cardiovascular disease, also accelerates the common IMT progression. The Sonographic measurement of carotid intima-media thickness is used as a valid simple and noninvasive method for the assessment of atherosclerosis disease.&#x0D; Also the ankle brachial index (ABI) is considered as a strong predictor for future cardiovascular events, and a golden standard for the diagnosis of peripheral arterial disease (PAD).&#x0D; Objectives: To estimate the validity of carotid IMT plus the ankle brachial index as a marker of atherosclerosis in diabetic patients.&#x0D; Materials and methods: This study involved (101) patients with type 2 Diabetes Mellitus, (37) with hypertension and (64) without hypertension. (46) normal volunteers represent the (Control group). The three groups were subjected to the routine laboratory tests including: fasting blood sugar, lipid profile. Measurements of blood pressure, BMI, waist circumference were taken, ECG, carotid intima media thickness and ABI by using Doppler ultrasound machine.&#x0D; Results: Statistical significant differences are found for the mean of the carotid intima media thickness, lipid profile, and systolic blood pressure for both arms and legs in type 2 D M patients with and without hypertension, and normal subjects. The diabetic patient's data revealed an increase in the carotid IMT more than the non diabetic subjects. Furthermore no significant differences were found to exist in ABI results among the diabetic and normal groups.&#x0D; Conclusion: The external examination by Doppler ultrasound of the carotid intima media thickness can be used to predict the occurrence of artery atherosclerosis, while ABI is less validated in this study with the selected type 2 diabetes mellitus patients without any cardiovascular disease.

Relationship between Inflammatory Markers and New Cardiovascular Events in Patients with Acute Myocardial Infarction Who Underwent Primary Angioplasty

Introduction:The determination of inflammation markers in circulation has enabled an important improvement in the study of cardiovascular diseases. It was tested the hypothesis that non-specific markers such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and fibrinogen may provide prognostic information in patients with acute myocardial infarction with persistent ST-segment elevation (STEMI) undergoing primary angioplasty (PCI).Methods:Patients: A cohort of 197 consecutive patients with STEMI undergoing primary PCI was enrolled, evaluating during hospitalization, the peak values of the following markers of inflammation: ESR, CRP and fibrinogen. A telephone follow-up has been made in order to investigate any possible new cardiovascular events after hospital discharge and the procedure performed.Results:Higher values of CRP were statistically associated with adverse future events as composite endpoint and with the single endpoint of death. Furthermore, higher age, presence of hypertension, history of previous cardiovascular events, were statistically significantly associated with cardiac events at follow up. In this group were also overrepresented subjects with anterior myocardial infarction in the anterior localization and with an EF ≤ 35% at discharge.Conclusions:CRP appears to be a predictor of future cardiovascular events, confirming that a pro-inflammatory state promotes the progression of atherosclerotic disease and its complications.

OP-018 INCREASED EPICARDIAL FAT THICKNESS IS ASSOCIATED WITH LOW GRADE SYSTEMIC INFLAMMATION IN METABOLIC SYNDROME

OZET etabolic syndrome (MetS) is a cluster of several cardiovascular risk factors and is associated with an increased risk for cardiovascular disease.[1] Visceral obesity and insulin resistance have been reported to play a key role in the development of MetS. [2] Based on previous reports, we believe that visceral adipose tissue may also be an important risk factor for MetS. Epicardial fat tissue, which is defined as the adipose tissue between the surface of the myocardium and the epicardium, can easily be visualized and measured using standard two-dimensional echocardiography.[3] Epicardial fat thickness (EFT) is used a measure of visceral adiposity rather than of general obesity.[4] EFT correlates with MetS, insulin resistance, coronary artery disease (CAD), and subclinical atherosclerosis, and may also serve as a simple tool for the prediction of cardiometabolic risk.[3,5,6] Epicardial fat tissue functions as lipid storage that secretes hormones, inflammatory cytokines, and chemokines, and is hypothesized to play a causative role in the development of MetS.[7] MetS is considered to be a pro-inflammatory condition, and most of the components of MetS, especially visceral obesity, are associated with low-grade systemic inflammation.[2] C-reactive protein (CRP) is one of the most important markers of inflammation, and elevated high sensitive CRP (hs-CRP) is known to be associated with cardiovascular risk factors[8,9] and is recognized as a strong predictor of future cardiovascular events.[10] In this study, we aimed to assess the relationship between the components of MetS, echocardiographic EFT, and hs-CRP levels. PATIENTS AND METHODS

CORONARY ARTERY CALCIUM PROGRESSION AS A STRONG PREDICTOR OF ADVERSE FUTURE CORONARY EVENTS

Coronary artery calcium has been shown to be the most powerful predictor of future cardiovascular events. We aimed to evaluate the prognostic value of increasing CAC scores for predicting future coronary events. This study includes 319 asymptomatic individuals with CAC score >10 at baseline. Each

The Prognostic Role of Late Gadolinium Enhancement Magnetic Resonance Imaging in Patients With Cardiomyopathy

Cardiovascular magnetic resonance imaging (CMRI) is currently considered part of standard care at many academic centres for the evaluation of patients with ischemic or nonischemic cardiomyopathy. While CMRI provides unparalleled diagnostic versatility for the assessment of myocardial function, perfusion, and tissue health, evidence supporting its prognostic value for the prediction of important cardiovascular events is now emerging. Given the low specificity of currently available clinical markers in patients with cardiomyopathy, more-robust biomarkers aimed at identifying those at high risk of sudden cardiac death and other relevant outcomes are desirable. Late gadolinium enhancement (LGE) CMRI offers the novel capacity to quantify the burden of myocardial fibrosis, a common pathophysiological end point of most cardiomyopathy states. As such, it has the potential to be a robust and ubiquitous marker of cardiovascular events related to the presence of advanced tissue disease. This review paper focuses on the evidence to date supporting LGE imaging as a tool for the prediction of future cardiovascular events in patients with ischemic and nonischemic cardiomyopathy.

Simultaneous Heart Rate Variability Monitoring Enhances the Predictive Value of Flow-Mediated Dilation in Ischemic Heart Disease

Endothelial dysfunction and autonomic nervous system imbalance are both risk markers of atherosclerotic vascular damage. The relationship between these 2 factors, however, has not been clarified concisely. Flow-mediated dilation (FMD) was measured in 47 patients with ischemic heart disease (IHD; mean age, 68.1±7.1 years) using an ultrasound semi-automatic measuring system (UNEXEF18G), and autonomic nervous system activity was evaluated by simultaneous measurements of heart rate variability. FMD was significantly correlated with standard deviation of normal-to-normal beats (r=0.33, P=0.022) and the power ratio of low-frequency power to high-frequency power (LF/HF; r=-0.38, P=0.0087). Furthermore, multiple regression analysis indicated that LF/HF was the most important predictor of the magnitude of FMD. This interaction was severely blunted by β-blockers and the presence of diabetes. Moreover, standardized FMD according to autonomic nervous system activity was a better predictor of future cardiovascular events than FMD. Subjects with cardiovascular events had a significantly smaller corrected FMD (event (+), 3.62±0.41; event (-), 5.10±2.35; P=0.001), and the higher corrected FMD was associated with longer event-free survival. Autonomic nervous system activity is an important regulatory factor of FMD in subjects with IHD. Assessment of this interaction can help provide more accurate risk stratification of subjects with IHD.

Clinical significance of provoked coronary spasm at chronic stage in patients who underwent successful complete coronary revascularization with first-generation drug-eluting stents

Background: Provoked spasm might have influence on cardiovascular events even after successful DES implantation. Methods and results: A consecutive 122 patients who underwent first-generation DES (CypherTM, and TaxusTM) implantation and had no residual stenosis at follow-up coronary angiography were included. All patients also underwent acetylcholine provocation test (ACh) at follow-up angiography. Age, sex, coronary risk factors (smoking, hypertension, diabetes mellitus, dyslipidemia), medication (calcium channel blockers, angiotensin receptor blockers, angiotensin converting enzyme inhibitors, nitrates, β blockers, statins), duration from stent implantation to follow-up angiography (15.5 ± 14.5 months), old myocardial infarction, Ach + were included as variables for multivariate analysis for cardiovascular events (angina pectoris without intervention, target lesion revascularization, acute myocardial infarction, definite or probable stent thrombosis, cardiac death, and stroke). ACh provocation test was positive in 64.8%. The following events occurred during a mean follow-up period of 26.9 ± 9.5 months; angina pectoris without intervention in 12, very late stent thrombosis in 1, acute myocardial infarction in 1, sudden death in 1, and stroke in 4. By Adjusted Cox hazard model, age was the independent predictor of future cardiovascular events. ACh was unbalanced data for Cox hazard model, and by logistic regression model, ACh was the strongest predictor. Conclusions: Coronary endothelial dysfunction at chronic stage is the strongest predictor of further prognosis in patients with first-generation DES.

Temporal changes of soluble ST2 after cardiovascular interventions

Soluble ST2 (sST2), a member of the IL-1 receptor family, has been proposed as a novel biomarker with predictive value for heart failure and mortality in patients suffering from cardiovascular diseases. The influence of clinical characteristics on variability of sST2 levels is relatively unexplored. Here, we studied the effect of cardiovascular interventions and clinical characteristics on plasma sST2 expression levels. In the current study, sST2 levels were assessed in the plasma of patients scheduled for coronary artery bypass grafting (CABG) (n=76), percutaneous coronary intervention (PCI) (n=68) or peripheral vascular surgery (n=27). Age was the only classical risk factor significantly correlating with sST2 levels. Soluble ST2 levels were significantly increased 1h after CABG (48 [33-70] vs. 61 [42-89] pg/mL, P=0·001) and increased even further after 24h (1116 [578-13666] pg/mL, P<0·001). An average threefold increase in sST2 levels was also observed in patients 24h after peripheral interventions (30 [21-41] vs. 98 [48-211] pg/mL, P<0·001). Two months after PCI, we found that sST2 levels were significantly higher compared with baseline levels (41 [29-61] vs. 48 [31-80] pg/mL, P=0·007, n=52). In addition, we did not observe an association between sST2 and any inflammatory or cardiac-specific markers that were measured in this study. Soluble ST2 increases significantly following cardiovascular interventions. The notion of a recent cardiovascular intervention is a strong determinant of sST2 levels and therefore needs to be taken into account when exploring sST2 as predictor of future cardiovascular events.

MR-proANP and MR-proADM for risk stratification of patients with acute chest pain

ObjectiveTo evaluate mid-regional pro-adrenomedullin (MR-proADM) and mid-regional pro-atrial natriuretic peptide (MR-proANP) as prognostic biomarkers in a representative ‘real world’ cohort of patients with suspected acute coronary syndrome (ACS).DesignProspective observational multicentre...

Abstract 9735: Endothelial Vasomotor Function in the Brachial Artery is Associated with Long-term Cardiovascular Events in Patients after Implantation of Drug Eluting-Stent

Endothelial dysfunctionin systemic arteries is a predictor of long-term coronary events. Although drug eluting-stent (DES) implantation aggravates coronary artery endothelial vasomotor dysfunction, it remains unclear endothelial dysfunction in systemic arteries provides prognostic information in coronary artery disease (CAD) patients after implantation of DES. Thus, we examined whether endothelial dysfunction may predict future cardiovascular events in CAD patients after implantation of DES. Methods: This study included 231 consecutive patients with newly diagnosed CAD who had elective and successful PCI with DES in de novo lesions of native coronary arteries. Measurement of FMD (expressed as percent dilation from baseline brachial artery diameter) during reactive hyperemia was performed by high-resolution ultrasound at entry (before PCI) and after 6months. All patients had individualized, optimized therapies including medications and recommended life style changes to reduce risk factors for CAD according to AHA guidelines. Patients were prospectively followed up until the occurrence of 1 of the following events: cardiovascular death, recurrent or refractory angina pectoris, nonfatal myocardial infarction, and ischemic stroke. The impairment of FMD was defined as &lt; 5.5% (mean minus 1SD of FMD in 100 age- and sex-matched normal subjects in our hospital). Results: Impaired FMD (&lt;5.5%) was in 86 (37%) patients after 6months. During a follow-up period of 30 ± 0.8 months, events occurred in 19 patients of the 86 patients with impaired FMD after 6months. Using multivariate Cox hazards analysis, impaired FMD after 6months was a predictor of future cardiovascular events that was independent of impaired FMD at entry, use of medications, age, and traditional CAD risk factors (odds ratio 2.9, 95%CI 1.3 - 6.2, p &lt; 0.01) Conclusions: Endothelial dysfunction in the brachial artery represents an adverse outcome in CAD patients after implantation of DES. Measurement of FMD may be useful for risk stratification in CAD patients after implantation of DES.

Utility of High-Sensitivity C-Reactive Protein Versus Coronary Artery Calcium for the Detection of Obstructive Stenoses in Stable Patients

The inflammatory biomarker high-sensitivity C-reactive protein (hs-CRP) has emerged as a predictor of future cardiovascular events. Screening for coronary artery calcium (CAC) is an alternative method for stratifying subjects by their cardiovascular risk. It is unclear, however, how hs-CRP compares with CAC scoring for the detection of obstructive coronary artery stenoses. We, thus, evaluated the association, if any, between hs-CRP and CAC scores for the detection of obstructive stenoses in a low-risk population with well-controlled traditional cardiovascular risk factors. In the present study of 1,079 stable subjects, 38 (3.5%) severely obstructive stenoses were found initially by coronary computed tomographic angiography and confirmed subsequently using invasive coronary angiography. The univariate predictors of severely obstructive coronary artery disease included the use of antihypertensive agents (p = 0.03), angina (p <0.001), and an elevated CAC score (p <0.001). The biomarker hs-CRP was not significantly associated with the presence of a severely obstructive stenosis. As the CAC scores increased, the frequency of obstructive stenosis also increased (p for trend <0.001). In contrast, the frequency of obstructive stenoses was low when CAC was not detected. This relation remained significant after adjustment for antihypertensive medication use and angina. In conclusion, hs-CRP was not useful for the prediction of obstructive stenoses in stable subjects. CAC was found to be a better predictor of obstructive heart disease than hs-CRP.

Abstract 19506: The Role of Mir-16 on Endothelial Dysfunction in Rat with Atherosclerotic Diet with a Chronic Model of Femoral Artery Occlusion and Carotid Balloon Injury

Background: Peripheral artery disease (PAD) is associated to coronary endothelial dysfunction and is an important predictor of future cardiovascular events. MicroRNAs play a critical role in modulating a variety of cellular processes by post-transcriptional regulation of their target genes. They are highly expressed in human endothelial cells (ECs), playing key role in essential biological processes. Thus, the aim of the present study was to evaluate the role, if any, of miRNAs in endothelial dysfunction in a model of PAD. Methods and Results: Male Wistar rats were provided of a standard atherogenic, high cholesterol diet and divided into 4 groups: no treatment (sham); rat subjected to vascular injury by balloon catheter (B.I.); rats underwent common femoral artery ligation (PAD); rats subjected to common femoral artery ligation and, after 21 days, subject to balloon injury (PAD+B.I.). RNA from intima was separately obtained from carotid arteries and evaluated for endothelial specific miRNAs using a stem-loop real-time-PCR. Interestingly, among the most important miRNAs expressed, real time RT-PCR showed an important up-regulation of miR-16 in ECs extracted by injured carotid artery of PAD+BI group respect the ECs of the others groups. A bioinformatics approach revealed highly conserved binding sites for miR-16 in the 3’UTR of SMAD7, an inhibitor of TGF-β1 signaling. The expression level of SMAD7 was measured in ECs treated with antagomiR-16 using immunoblotting analysis. Up-regulation of miR-16 revealed a reduction of SMAD7 levels. Also, we evaluated the effects of miR-16 inhibition in ECs on mRNA and protein levels of eNOS and NF-kB, regulators of endothelial dysfunction. Real-time PCR showed an increased expression of eNOS mRNA in ECs treated with antagomiR-16. Furthermore, immunoblotting revealed increased eNOS protein production as well as its activation in ECs by miR-16 inhibition. Finally, we showed an increased NF-kB activation in ECs after up-regulation of miR-16. Conclusions: Our data demonstrated that in rat with PAD and atherosclerotic diet, miR-16 is up-regulated in endothelial cell of carotid arteries after balloon injury. This findings might of importance to assess future strategies in patients with PAD.

Ultrasonic Tissue Characterization of Carotid Plaque Improves the Prediction of Cardiovascular Events in Diabetic Patients

OBJECTIVEThe aim of this study is to evaluate whether noninvasive ultrasonic tissue characterization of carotid plaque using integrated backscatter (IBS) analysis can be a predictor of future cardiovascular events (CVE) in asymptomatic type 2 diabetic patients.RESEARCH DESIGN AND METHODSWe prospectively evaluated the association between Calibrated-IBS value, an ultrasonic marker for tissue characteristics of carotid plaque, and CVE in 85 asymptomatic type 2 diabetic patients with carotid plaque.RESULTSThe median follow-up period was 7.9 years, and there were 20 new CVE. The risk of CVE was significantly higher in the subjects with low Calibrated-IBS values (<−17.1 dB; n = 42) as compared with those with high values (≥−17.1 dB; n = 43) (P = 0.004, log-rank test). Cox proportional hazards regression analysis revealed that both Calibrated-IBS value (hazard ratio [HR] 0.802 [95% CI 0.710–0.906]; P < 0.0001) and plaque thickness (1.938 [1.170–3.213]; P = 0.010) were independently associated with CVE, even after adjustment for the 10-year risk for a general cardiovascular disease estimated by Framingham risk scoring (FRS). Time-dependent receiver operating characteristic curve analysis for CVE at 10 years after the baseline examinations revealed that area under the curve for Calibrated-IBS was 0.76 (0.60–0.90) and substantially higher than those for plaque thickness (0.60 [0.45–0.79]) and FRS (0.60 [0.40–0.78]). These analyses also revealed that the addition of both plaque thickness and Calibrated-IBS value to conventional risk factors significantly improved the event prediction.CONCLUSIONSCalibrated-IBS value could improve the risk prediction of CVE in asymptomatic type 2 diabetic patients with carotid plaque.

Predicting Coronary Heart Disease: From Framingham Risk Score to Ultrasound Bioimaging

Atherosclerosis is the leading cause of death and disabling disease. Whereas risk factors are well known and constitute therapeutic targets, they are not useful for prediction of risk of future myocardial infarction, stroke, or death. Therefore, methods to identify atherosclerosis itself have been tested and found useful (ie, coronary calcium detection by computed tomography scanning, reduction in ankle-brachial index, and ultrasound scanning of the carotid arteries). This review will focus on the latter technique. Detection of thickened carotid intima-media by ultrasound has been used in many large epidemiological studies, but although it has been found to be associated with increased risk of cardiovascular death, its clinical utility is limited. Detection of carotid plaque has, on the other hand, been found to be associated with a substantial risk of future events. Similarly, detection of plaque in the femoral arteries is associated with increased risk, and plaque in the femoral as well as carotid arteries predicts even higher risk. Furthermore, quantification of plaque size (plaque area), such as quantification of amount of coronary calcium on computed tomography scanning, improves predictability-the larger the plaques, the higher the risk. So far, studies using ultrasound all have been performed with 2-dimensional ultrasound imaging. Recently, 3-dimensional ultrasound imaging has been introduced, which allows for more accurate quantification of atherosclerosis. Small studies pioneering its use have indicated the utility of measuring changes in vessel-wall volume and plaque volume with respect to treatment effect. The High-Risk Plaque Initiative BioImage Study is currently investigating the predictive value of total carotid plaque volume with respect to prediction of future cardiovascular events.

Arterial stiffening: Causes and consequences

Increased arterial stiffness, as measured by pulse wave velocity, is increasingly recognised as an important predictor of future cardiovascular events. At present, the mechanisms leading to stiffening of large arteries and the processes underlying the association between arterial stiffness and cardiovascular disease remain unclear. One suggestion is that stiffening may be a caused by atherosclerosis along the aorta, explaining its association with cardiovascular disease. However, age-related stiffening of large arteries can occur independently of atherosclerosis and development of atherosclerosis does not necessarily contribute to increased aortic stiffness. Vascular calcification, extracellular matrix degradation and inflammation are likely to contribute to arterial stiffening. One consequence of increased large artery stiffness is an increase in pulse pressure, which, in older subjects, is the blood pressure components most closely correlated with cardiovascular events. The association between arterial stiffness and cardiovascular events may be explained, at least in part, by the adverse haemodynamic consequences of increased stiffness. This review summarises the potential mechanisms of arterial stiffening and its haemodynamic consequences.

Characteristics of High-Risk Plaques as Identified on Coronary Computed Tomography Angiography

Computed tomography (CT) is a non-invasive imaging technique that permits the assessment of coronary arteries for the presence of stenosis and plaque. Improved image quality with the newest CT technology has resulted in the ability to perform detailed analysis of coronary atherosclerotic plaque. Multiple cross-sectional studies described morphologic features of plaques associated with acute coronary syndrome. Further, the prognostic value of coronary plaque characteristics for the prediction of future cardiovascular events has been explored. In this article, we review the available literature on characteristics of high-risk plaques as identified by coronary CT angiography.

Blood pressure as a drug target: what should we be measuring?

Clinicians and researchers have traditionally relied on esti-mates of systolic and diastolic pressure in the brachialartery to predict cardiovascular risk and guide individualtherapy. There is overwhelming evidence that usual BPmeasured in this way is a powerful predictor of future car-diovascular events [1],but the mechanistic link(s) betweenpressure and pathology (atheromatous disease and arte-rial thrombosis) is (are) incompletely understood.The dis-tinguished statistician Ronald Fisher (of‘Fisher’s exact test’)pointed out the excellent correlation between the inci-dence of lung cancer in the twentieth century and sales ofwashing machines in a tobacco-industry funded pamphletmocking the then available evidence that smoking causescancer. His point was that association does not prove cau-sality, but nor does it disprove it, and the subsequent evi-dence assembled by Richard Doll resolved the smoking/cancer issue definitively.Evidence from placebo-controlled randomized trialsshows that experimental interventions that lower brachialartery blood pressure also reduce cardiovascular events[2]. This not only underpins clinical decision making butalso supports the notion that high BP actually causes car-diovascular disease,rather than being a consequence of it.However, this is not the end of the story. Systolic and dias-tolic BP (SBP,DBP) are correlated with one another,both arelowered by drug treatment, but DBP behaves strikinglydifferently from SBP in predicting future risk.Subjects aged50–79 years in the Framingham cohort were groupedaccording to SBP ( 160 mmHg) tocontrol for the strong association between SBP on DBP andreduce the effect of SBP on risk within each group [3].DBPin each group was found to be