100,000 Patient Meta-Analysis Shows Carotid Intima-Media Thickness Progression Can Be Used as a Surrogate Marker for Cardiovascular Risk

Sahar Memar Montazerin, MD
By Sahar Memar Montazerin, MD on

A recent meta-analysis of clinical trials with more than 100,000 patients has shown that the carotid intima-media thickness (cIMT) progression can be used as a surrogate marker for cardiovascular risk in the clinical trials. The results of this study published in Circulation. According to Dr. Willeit, the assessment of cIMT progression can provide a link for the development and license of new therapies for cardiovascular disease.

Carotid intima-media thickness (cIMT), a marker of early atherosclerosis, can be measured via ultrasound imaging. Recent studies have shown the efficacy of therapeutic interventions in slowing the progression of cIMT. However, the efficacy of these interventions in the CVD risk reduction remains unclear. Dr. Willeit and his colleagues conducted this study to address this uncertainty.

This comprehensive meta-analysis of randomized clinical trials included studies with the data on the measured cIMT at the baseline and follow-up visits as well as the incident of CVD outcomes. cIMT was defined as mean values at the common-carotid-artery or, in case of unavailability, maximum values at the common-carotid-artery or cIMT at other parts of the carotid artery. CVD events including myocardial infarction, stroke, revascularization procedures, or fatal CVD were considered the primary outcomes of the study.

A total of 119 studies involving 100,667 participants (mean age 62 years, 42% female)  included in the analysis. Upon a mean follow-up duration of 3.7 years, 12,038 patients experienced the primary outcomes. The study demonstrated that each 10 μm/year reduction of cIMT progression via therapeutic interventions would result in relative risk for CVD of 0.91 (95% credible interval (CI):0.87-0.94). These interventions also reduced the CVD risk and resulted in relative risk of  0.92 (95% CI:0.87-0.97) independent of their effects on cIMT progression. The study estimated the relative risk for a greater reduction of cIMT progression and yielded a relative risk of 0.63 (95% CI:0.52-0.74) for 40 μm/year reduction. It worth mentioning that the results of the study remained similar across different statistical analyses categorizing trials by type of intervention, time to ultrasound follow-up, type of cIMT measurement, and proportion of female patients. 

This study has some limitations that warrant consideration. First, the type of therapeutic intervention was different across the included trials and this may affect the cIMT surrogate value. Second, the participants of the included trials had different comorbidities.

Finally, the results of this large-scale meta-analysis showed that therapeutic interventions on cIMT progression were associated with a change in CVD risks. Using cIMT progression as a substitute for CVD risks may facilitate the development of new therapies for cardiovascular disease.

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