Preliminary Results Indicate Carotid Intima-Media Thickness Is Biomarker of Atherosclerosis

Title: Preliminary Results Indicate Carotid Intima-Media Thickness Is Biomarker of Atherosclerosis: Presented at DALM


"Preliminary Results Indicate Carotid Intima-Media Thickness Is Biomarker of Atherosclerosis: Presented at DALM"By Crina Frincu-Mallos, PhD NEW YORK, NY -- October 12, 2007 -- Overall data from the IMPROVE trial support the concept that carotid intima-media thickness (IMT) and IMT progression constitute novel biomarkers of atherosclerotic disease, according to a study presented here on at the XVI International Symposium on Drugs Affecting Lipid Metabolism (DALM).


Elena Tremoli, MD, Professor and Director, Department of Pharmacological Sciences, University of Milan, and Research Coordinator, Centro Cardiologico Monzino, IRCCS, Milan, Italy, presented the data on October 6.


The Carotid IMT and IMT-PROgression as Predictors of Vascular Events in a High Risk European Population (IMPROVE) study is an ongoing prospective, multicentre, longitudinal study with 3,711 patients from six European countries. All patients were classified as being at high risk for cardiovascular disease with at least three vascular risk factors, said Dr. Tremoli.


Patient enrollment ended in April 2005; patients were recruited from Finland (n=1,050), Sweden (n=533), The Netherlands (n=532), France (n=501), and Italy (n=1,095).


This patient population consists of men and women in approximately a 1:1 ratio (aged 64 +- 5 years). The largest percentage of patients have familial hypercholesterolaemia (78.6%); 23.9% of patients have diabetes.


The study is designed to determine whether it is feasible to predict new vascular events based on the progression of carotid IMT, "alone or after integration with conventional and nonconventional risk factors," explained Dr. Tremoli. IMT, a novel surrogate marker of atherosclerosis, is measured by high-resolution B-mode ultrasound.


Preliminary results indicate a significant connection between high sensitivity C-reactive protein (hs-CRP) and gender in the overall population. "Hs-CRP is a determinant of carotid IMT in men only," said Dr. Tremoli. However, cigarette smoking unmasks the association between hs-CRP and carotid IMT in women, she added.

The study monitored the occurrence of cardiovascular events over a period of 36 months.

A total of 135 first events occurred in the 3,393 patients enrolled in the trial, the most common event being angina pectoris (n=45), angioplasty/stent (n=39), stroke (n=21), and coronary bypass (n=16).


In addition, the researchers observed a geographic (North-South) gradient in carotid IMT when they analysed the baseline data.


The preliminary data support the concept that carotid IMT is a biomarker of atherosclerotic disease, concluded Dr. Tremoli. Data on the predictive capacity of carotid IMT-progression should be available by the end of next year.


Funding for this study was provided by the Italian Ministry of Health, European Commission, and the IMPROVE project.


Presentation title: Carotid Intima Media Thickness as Marker of Atherosclerosis: Results of the IMPROVE Study. Abstract 159.

Statin Treatment in Children With Familial Hypercholesterolemia

Statin Treatment in Children With Familial Hypercholesterolemia
The Younger, the Better


Published online before print July 30, 2007, doi:10.1161/CIRCULATIONAHA.106.671016


Jessica Rodenburg, MD, PhD; Maud N. Vissers, PhD; Albert Wiegman, MD, PhD; A. S. Paul van Trotsenburg, MD, PhD; Anouk van der Graaf, MD; Eric de Groot, MD, PhD; Frits A. Wijburg, MD, PhD; John J.P. Kastelein, MD, PhD; Barbara A. Hutten, PhD

From the Departments of Vascular Medicine (J.R., M.N.V., A.v.d.G., E.d.G., J.J.P.K.), Paediatrics (A.W., A.S.P.v.T., F.A.W.), and Clinical Epidemiology, Biostatistics and Bioinformatics (B.A.H.), Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.


Background— We previously demonstrated in a randomized placebo-controlled trial that 2-year pravastatin treatment induced a significant regression of carotid intima-media thickness (IMT) in 8- to 18-year-old children with familial hypercholesterolemia. Subsequently, we continued to follow up these children to explore the relation between the age of statin initiation and carotid IMT after follow-up on statin treatment. We also examined safety aspects of statin therapy during this long-term follow-up.

Methods and Results— All 214 children who initially participated in the previous placebo-controlled study were eligible for the follow-up study. After completion of the placebo-controlled study, all children continued treatment with pravastatin 20 or 40 mg, depending on their age. Blood samples were taken on a regular basis for lipids and safety parameters, and a carotid IMT measurement was performed after an average treatment period of 4.5 years. Follow-up data for 186 children were available for the statistical analyses. Multivariate analyses revealed that age at statin initiation was an independent predictor for carotid IMT after follow-up with adjustment for carotid IMT at initiation of statin treatment, sex, and duration of treatment. Early initiation of statin treatment was associated with a subsequently smaller IMT. Furthermore, no serious laboratory adverse events were reported during follow-up, and statin treatment had no untoward effects on sexual maturation.

Conclusions— These data indicate that early initiation of statin treatment delays the progression of carotid IMT in adolescents and young adults. The present study shows for the first time that early initiation of statin therapy in children with familial hypercholesterolemia might be beneficial in the prevention of atherosclerosis in adolescence.

Primary source:

Circulation: Journal of the American Heart AssociationSource reference: Rodenburg J, et al "Statin Treatment in Children With Familial Hypercholesterolemia: The Younger, the Better" Circulation 2007;116: 664-668.