Association between Low-Density Lipoprotein Cholesterol and Vascular Biomarkers in Primary Prevention.

Several noninvasive vascular biomarkers have been proposed to improve risk stratification for atherothrombotic events. To identify biomarkers suitable for detecting intermediate-risk individuals who might benefit from lipid-lowering treatment in primary prevention, the present study tested the association of plasma LDL-cholesterol with coronary artery calcification (CAC) Agatston score, high carotid and femoral intima-media thickness (IMT), low carotid distensibility and high carotid-femoral pulse-wave velocity in 260 asymptomatic individuals at intermediate cardiovascular risk and without diabetes and lipid-lowering treatment. High or low vascular biomarkers were considered when their value was above the 95th or below the 5th percentile, respectively, of the distribution in the healthy or in the study population. LDL-cholesterol was independently associated with the CAC score = 0 (OR 0.67; 95%CI 0.48-0.92, p = 0.01), CAC score > 100 (1.59; 1.08-2.39, p = 0.01) and high common femoral artery (CFA) IMT (1.89; 1.19-3.06, p < 0.01), but not with other biomarkers. Our data confirm that in individuals at intermediate risk, lipid-lowering treatment can be avoided in the presence of a CAC score = 0, while it should be used with a CAC score > 100. CFA IMT could represent a useful biomarker for decisions regarding lipid-lowering treatment. However, sex- and age-specific reference values should be established in a large healthy population.

Comparison between Carotid Distensibility-Based Vascular Age and Risk-Based Vascular Age in Middle-Aged Population Free of Cardiovascular Disease.

The concept of vascular age (VA) was proposed to provide patients with an understandable explanation of cardiovascular (CV) risk and to improve the performance of prediction models. The present study compared risk-based VA derived from Framingham Risk Score (FRS) and Systematic Coronary Risk Estimation (SCORE) models with value-based VA derived from the measurement of the common carotid artery (CCA) distensibility coefficient (DC), and it assessed the impact of DC-based VA on risk reclassification. In 528 middle-aged individuals apparently free of CV disease, DC was measured by radiofrequency-based arterial wall tracking that was previously utilised to establish sex- and age-specific reference values in a healthy population. DC-based VA represented the median value (50th percentile) for given sex in the reference population. FRS-based and SCORE-based VA was calculated as recommended. We observed a good agreement between DC-based and FRS-based VA, with a mean difference of 0.46 ± 12.2 years (p = 0.29), while the mean difference between DC-based and SCORE-based VA was higher (3.07 ± 12.7 years, p < 0.0001). When only nondiabetic individuals free of antihypertensive therapy were considered (n = 341), the mean difference dropped to 0.70 ± 12.8 years (p = 0.24). Substitution of chronological age with DC-based VA in FRS and SCORE models led to a reclassification of 28% and 49% of individuals, respectively, to the higher risk category. Our data suggest that the SCORE prediction model, in which diabetes and antihypertensive treatment are not considered, should be used as a screening tool only in healthy individuals. The use of VA derived from CCA distensibility measurements could improve the performance of risk prediction models, even that of the FRS model, as it might integrate risk prediction with additional risk factors participating in vascular ageing, unique to each individual. Prospective studies are needed to validate the role of DC-based VA in risk prediction.

Noninvasive carotid pressure-diameter loops to identify viscoelastic properties in ageing, hypertension and type 2 diabetes.

OBJECTIVES: Arterial stiffness as pulse wave velocity (PWV) predicts cardiovascular events independently of blood pressure (BP). PWV does not distinguish between stiffness in systole and diastole. This cross-sectional study aimed to test the hypothesis that viscous and elastic carotid wall properties differ between systole and diastole, distinguishing effects of ageing, hypertension and T2 diabetes (T2DM). METHODS: We examined carotid visco-elasticity in 307 people (180 men), with hypertension alone (n = 69), combined hypertension/T2DM (H-T2DM, n = 99), normotensive (N-T2DM, n = 25) and healthy controls (n = 114). Diameter (D)/pressure (P) waveforms were measured at right /left common carotid arteries, respectively. Local carotid PWV and distensibility in systole and diastole were evaluated by the D2P-loop method, and wall viscosity from hysteresis, the area (HA) within the P--D loop, as a dynamic measure of systolic loading and diastolic unloading. RESULTS: Controls' hysteresis fell quadratically with age (R2 = 0.23, P < 0.001). Yet mean HA in hypertensive patients (0.95, 95% CI 0.65-1.23) was six-fold higher than in age-matched controls (0.14, -0.20 to 0.49, P < 0.001) with a 2.5× difference between diastolic (dDs) to systolic (sDs) distensibility (P < 0.05) in hypertensive patients. HA was higher in hypertensive patients and H-T2DMs (0.80, 0.58-1.04) than N-T2DMs (0.20, -0.17 to 0.54, P < 0.05), but similar between controls and N-T2DMs. BP-adjusted carotid diameters in all T2DM were significantly greater compared with controls and hypertensive patients. CONCLUSION: Higher BP increased wall viscosity, hysteresis and relative difference between systolic and diastolic distensibility across groups. Carotid diameters were increased in all T2DMs, more in H-T2DM, probably altering BP-flow dynamics in T2DM.

Genetic and nutritional factors determining circulating levels of lipoprotein(a): results of the "Montignoso Study".

Increasing evidence shows an association between high lipoprotein(a) [Lp(a)] levels and atherothrombotic diseases. Lp(a) trait is largely controlled by kringle-IV type 2 (KIV-2) size polymorphism in LPA gene, encoding for apo(a). Environmental factors are considered to determinate minor phenotypic variability in Lp(a) levels. In the present study, we investigated the possible gene-environment interaction between KIV-2 polymorphism and Mediterranean diet adherence or fish weekly intake in determining Lp(a) levels. We evaluated Lp(a), KIV-2 polymorphism, fish intake and Mediterranean diet adherence in 452 subjects [median age (range) 66 (46-80)years] from Montignoso Heart and Lung Project (MEHLP) population. In subjects with high KIV-2 repeats number, influence of Mediterranean diet adherence in reducing Lp(a) levels was observed (p = 0.049). No significant difference in subjects with low KIV-2 repeats according to diet was found. Moreover, in high-KIV-2-repeat subjects, we observed a trend towards influence of fish intake on reducing Lp(a) levels (p = 0.186). At multivariate linear regression analysis, high adherence to Mediterranean diet remains a significant and independent determinant of lower Lp(a) levels (ß = - 64.97, standard error = 26.55, p = 0.015). In conclusion, this study showed that only subjects with high KIV-2 repeats can take advantage to lower Lp(a) levels from correct nutritional habits and, in particular, from Mediterranean diet.

Radiofrequency-based wall tracking for noninvasive assessment of local carotid pulse pressure: comparison with applanation tonometry and association with organ damage.

OBJECTIVES: Central pulse pressure (PP) has been suggested a better predictor of cardiovascular risk than brachial PP, and its routine noninvasive assessment can be useful for risk stratification. The present study evaluated the capability of a radiofrequency-based carotid wall tracking to estimate central PP from distension curves, comparing the values of carotid PP as obtained by wall tracking with those provided by applanation tonometry. Furthermore, the associations of carotid PP with intermediate markers of cardiovascular risk, like carotid intima-media thickness (IMT) and left ventricular mass (LVM), were assessed. METHODS: Carotid PP was measured by wall tracking and applanation tonometry during the same session in 346 individuals (healthy controls, patients with hypertension and diabetes). IMT was measured in all individuals and LVM was measured in 253. RESULTS: Carotid PP values as measured by wall tracking and applanation tonometry were highly correlated [r = 0.87; slope 0.90 (0.85-0.95); P < 0.0001; mean difference = 3.1 ±â€Š6.8 mmHg], and were independently determined by the same variables (age, heart rate, triglycerides, blood pressure-lowering therapy). Carotid IMT and LVM correlated more strongly with carotid PP (r = 0.44 and 0.50; P < 0.0001 for both) than with brachial PP (r = 0.34 and 0.42; P < 0.0001 for both). Patients with carotid PP at least 50 mmHg had higher IMT, LVM, and prevalence of LV hypertrophy than those with PP less than 50 mmHg (P = 0.0001 to <0.0001). CONCLUSIONS: Local carotid PP as estimated by wall tracking is comparable to that obtained by applanation tonometry, and it shows a better association with target organ damage than brachial blood pressure. Assessment of carotid PP during routine ultrasound examination of extracranial carotid tree may provide additional information for individual risk stratification.

Multimodality imaging in preoperative assessment of left atrial appendage transcatheter occlusion with the Amplatzer Cardiac Plug.

AIMS: Percutaneous left atrial appendage occlusion (LAAO) with the Amplatzer Cardiac Plug (ACP) emerged as a valid alternative in patients with a formal contraindication to oral anticoagulant therapy. Transoesophageal echocardiography (TEE), cardiac computed tomography angiography (CCTA), intracardiac echocardiography (ICE), and conventional cardiac angiography (CCA) are used to evaluate LAA diameters. The aim of our study was to compare pre- and intraprocedural imaging techniques in determining the correct selection of the device size, with a retrospective evaluation of the results obtained at post-procedural CCTA follow-up. METHODS AND RESULTS: Between September 2009 and July 2013, 66 consecutive patients underwent to LAAO with the ACP at our institution. Preoperative LAA evaluation was realized with TEE, CCTA, ICE, and CCA. Fifty-eight (58) patients underwent to post-procedural CCTA to confirm the LAA complete exclusion, the number and extent of the residual leaks, and the positioning of the device. LAA diameters measured by CCTA correlate with the diameters obtained with CCA and ICE, but they are sized slightly larger than the others. TEE has a lower correlation with every other imaging method and a likely tendency to underestimate. The distribution of the leaks and the positioning of the device in post-procedural CCTA show no substantial differences between the devices used greater or equal to the one selected with CCTA in terms of LAA exclusion. CONCLUSION: The sizing of the device decided using CCTA in the phase of maximum LAA expansion reduces the risk of high-flow leaks and device malposition due to undersizing.