Epidemiology and Prevention Dietary Intervention to Reverse Carotid Atherosclerosis

Background—It is currently unknown whether dietary weight loss interventions can induce regression of carotid atherosclerosis. Methods and Results—In a 2-year Dietary Intervention Randomized Controlled Trial–Carotid (DIRECT-Carotid) study, participants were randomized to low-fat, Mediterranean, or low-carbohydrate diets and were followed for changes in carotid artery intima-media thickness, measured with standard B-mode ultrasound, and carotid vessel wall volume (VWV), measured with carotid 3D ultrasound. Of 140 complete images of participants (aged 51 years; body mass index, 30 kg/m; 88% men), higher baseline carotid VWV was associated with increased intima-media thickness, age, male sex, baseline weight, blood pressure, and insulin levels (P 0.05 for all). After 2 years of dietary intervention, we observed a significant 5% regression in mean carotid VWV ( 58.1 mm 95% confidence interval, 81.0 to 35.1 mm; P 0.001), with no differences in the low-fat, Mediterranean, or low-carbohydrate groups ( 60.69 mm, 37.69 mm, 84.33 mm, respectively; P 0.28). Mean change in intima-media thickness was 1.1% (P 0.18). A reduction in the ratio of apolipoprotein B100 to apolipoprotein A1 was observed in the low-carbohydrate compared with the low-fat group (P 0.001). Participants who exhibited carotid VWV regression (mean decrease, 128.0 mm; 95% confidence interval, 148.1 to 107.9 mm) compared with participants who exhibited progression (mean increase, 89.6 mm; 95% confidence interval, 66.6 to 112.6 mm) had achieved greater weight loss ( 5.3 versus 3.2 kg; P 0.03), greater decreases in systolic blood pressure ( 6.8 versus 1.1 mm Hg; P 0.009) and total homocysteine ( 0.06 versus 1.44 mol/L; P 0.04), and a higher increase of apolipoprotein A1 ( 0.05 versus 0.00 g/L; P 0.06). In multivariate regression models, only the decrease in systolic blood pressure remained a significant independent modifiable predictor of subsequent greater regression in both carotid VWV ( 0.23; P 0.01) and intima-media thickness ( 0.28; P 0.008) levels. Conclusions—Two-year weight loss diets can induce a significant regression of measurable carotid VWV. The effect is similar in low-fat, Mediterranean, or low-carbohydrate strategies and appears to be mediated mainly by the weight loss–induced decline in blood pressure. Clinical Trial Registration—http://www.clinicaltrials.gov. Unique Identifier: NCT00160108. (Circulation. 2010;121:1200-1208.)