Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.

BACKGROUND: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk. METHODS: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used. The primary outcome was a combined CVD end point defined as myocardial infarction, stroke, revascularization procedures, or fatal CVD. We estimated intervention effects on cIMT progression and incident CVD for each trial, before relating the 2 using a Bayesian meta-regression approach. RESULTS: We analyzed data of 119 randomized, controlled trials involving 100 667 patients (mean age 62 years, 42% female). Over an average follow-up of 3.7 years, 12 038 patients developed the combined CVD end point. Across all interventions, each 10 µm/y reduction of cIMT progression resulted in a relative risk for CVD of 0.91 (95% Credible Interval, 0.87-0.94), with an additional relative risk for CVD of 0.92 (0.87-0.97) being achieved independent of cIMT progression. Taken together, we estimated that interventions reducing cIMT progression by 10, 20, 30, or 40 µm/y would yield relative risks of 0.84 (0.75-0.93), 0.76 (0.67-0.85), 0.69 (0.59-0.79), or 0.63 (0.52-0.74), respectively. Results were similar when grouping trials by type of intervention, time of conduct, time to ultrasound follow-up, availability of individual-participant data, primary versus secondary prevention trials, type of cIMT measurement, and proportion of female patients. CONCLUSIONS: The extent of intervention effects on cIMT progression predicted the degree of CVD risk reduction. This provides a missing link supporting the usefulness of cIMT progression as a surrogate marker for CVD risk in clinical trials.

A Randomized Trial Comparing Short versus Prolonged Hemostasis with Rescue Recanalization by Ipsilateral Ulnar Artery Compression: Impact on Radial Artery Occlusion-The RESCUE-RAO Trial.

BACKGROUND: Despite the enormous benefits of radial access, this route is associated with a risk of radial artery occlusion (RAO). OBJECTIVE: We compared the incidence of RAO in patients undergoing transradial coronary angiography and intervention after short versus prolonged hemostasis protocol. Also we assessed the efficacy of rescue 1-hour ipsilateral ulnar artery compression if RAO was observed after hemostasis. Material and Methods. Patients referred for elective transradial coronary procedures were eligible. After 6 F radial sheath removal, patients were randomized to short (3 hours) (n = 495) or prolonged (8 hours) (n = 503) hemostasis and a simple bandage was placed over the puncture site. After hemostasis was completed, oximetry plethysmography was used to assess the patency of the radial artery. RESULTS: One thousand patients were randomized. Baseline characteristics were similar between both groups with average age 61.4 ± 9.4 years (71% male) and PCI performed on half of the patients. The RAO rate immediately after hemostasis was 3.2% in the short hemostasis group and 10.1% in the prolonged group (p < 0.001). Rescue recanalization was successful only in the short group in 56.2% (11/19); at hospital discharge, RAO rates were 1.4% in the short group and 10.1% in the prolonged group (p < 0.001). CONCLUSION: Shorter hemostasis was associated with significantly less RAO compared to prolonged hemostasis. Rescue radial artery recanalization was effective in > 50%, but only in the short hemostasis group.

Carotid and Aortic Stiffness in Patients with Heterozygous Familial Hypercholesterolemia.

BACKGROUND: The role of plasma cholesterol in impairing arterial function and elasticity remains unclear. We evaluated arterial stiffness, measured locally in the common carotid artery by high-resolution echo-tracking, and aortic stiffness, using carotid-femoral pulse wave velocity (PWV) (the "gold-standard" measurement of arterial stiffness), in treatment-naive patients with heterozygous familial hypercholesterolemia (FH). METHODS: The study included 66 patients with FH (10-66 years old) and 57 first-degree relatives without FH (11-61 years old). Carotid-femoral PWV was determined by SphygmoCor (AtCor, Australia). The parameters of carotid stiffness ß-index, Peterson elastic modulus and local PWV were assessed with regard to the common carotid artery at a distance of 1cm from the bifurcation (AlokaProsound Alpha7, Japan). RESULTS: FH patients showed significantly higher ß-index (6.3(4.8-8.2) vs. 5.2(4.2-6.4), p = 0.005), Ep (78(53-111) kPa vs. 62(48-79) kPa, p = 0.006), local PWV (5.4(4.5-6.4) m/c vs. 4.7(4.2-5.4) m/c, p = 0.005), but comparable values of carotid-femoral PWV (6.76(7.0-7.92) m/c vs. 6.48(6.16-7.12) m/c, p = 0.138). Carotid arteries and the aorta stiffened with age in patients with FH, but after 30 years, carotid arteries stiffened more significantly than the aorta. CONCLUSIONS: Our study demonstrated that treatment-naive patients with FH had stiffer carotid arteries than their relatives, but showed no difference in aortic stiffness. We also found out that the rate of reduction of elasticity of the aorta and carotid arteries in FH patients varies: it is observed earlier in carotid arteries than in the aorta.

Normative values for carotid intima media thickness and its progression: Are they transferrable outside of their cohort of origin?

BACKGROUND: The clinical use of carotid intima media thickness (cIMT) requires normal values, which may be subject to variation of geographical factors, ethnicity or measurement details. The influence of these factors has rarely been studied. The aim of this study was to determine whether normative cIMT values and their association with event risk are generalizable across populations. DESIGN: Meta-analysis of individual participant data. METHOD: From 22 general population cohorts from Europe, North America and Asia we selected subjects free of cardiovascular disease. Percentiles of cIMT and cIMT progression were assessed separately for every cohort. Cox proportional hazards models for vascular events were used to estimate hazard ratios for cIMT in each cohort. The estimates were pooled across Europe, North America and Asia, with random effects meta-analysis. The influence of geography, ethnicity and ultrasound protocols on cIMT values and on the hazard ratios was examined by meta-regression. RESULTS: Geographical factors, ethnicity and the ultrasound protocol had influence neither on the percentiles of cIMT and its progression, nor on the hazard ratios of cIMT for vascular events. Heterogeneity for percentiles of cIMT and cIMT progression was too large to create meaningful normative values. CONCLUSIONS: The distribution of cIMT values is too heterogeneous to define universal or regional population reference values. CIMT values vary widely between different studies regardless of ethnicity, geographic location and ultrasound protocol. Prediction of vascular events with cIMT values was more consistent across all cohorts, ethnicities and regions.

Ultrasound markers that describe plaques are more sensitive than mean intima-media thickness in patients with familial hypercholesterolemia.

A widely adopted ultrasound surrogate marker for predicting cardiovascular risk is mean intima-medial thickness (mean-IMT). There are, however, certain limitations to this methodology. We compared the severity of carotid atherosclerosis in adult patients with high cardiovascular risk (patients with familial hypercholesterolemia [FH] and without previous statin treatment) and in their adult FH-free first-degree relatives using not only mean-IMT, but also maximum-IMT, plaque number, plaque score and percent area stenosis. Mean-IMT has not differed in both groups (0.64 ± 0.18 mm vs. 0.58 ± 0.13 mm in the control group, p = 0.349). Maximum-IMT (0.99 ± 0.35 vs. 0.76 ± 0.19, p = 0.0057), plaque number (3 ± 3 vs. 1 ± 2, p = 0.0009), plaque score (5.14 ± 4.97 mm vs. 1.58 ± 3.09 mm, p = 0.0009) and percent area stenosis (38% ± 22% vs. 12% ± 20%, p = 0.0004) were significantly higher for FH patients than for their relatives. We have demonstrated that plaque number, plaque score and percent area stenosis markers were more sensitive than mean-IMT for cardiovascular risk estimation in patients with familial hypercholesterolemia.