BackgroundAlthough statins reduce cardiovascular events, residual risk remains. Therefore, additional modalities are needed to reduce risk. We evaluated the effect of eicosapentaenoic acid and docosahexaenoic acid in pharmacologic doses added to statin treatment on coronary artery plaque volume.Methods and ResultsA total of 285 subjects with stable coronary artery disease on statins were randomized to omega‐3 ethyl‐ester (1.86 g of eicosapentaenoic acid and 1.5 g of docosahexaenoic acid daily) or no omega‐3 (control) for 30 months. Coronary plaque volume was assessed by coronary computed tomographic angiography. Mean (SD) age was 63.0 (7.7) years; mean low‐density lipoprotein cholesterol ≤80 mg/dL. In the intention‐to‐treat analysis, our primary endpoint, noncalcified plaque volume, was not different between groups (P=0.14) but approached significance in the per protocol analysis (P=0.07). When stratified by age in the intention‐to‐treat analysis, younger omega‐3 subjects had significantly less progression of the primary endpoint, noncalcified plaque (P=0.013), and fibrous, calcified and total plaque. In plaque subtype analysis, controls had significant progression of fibrous plaque compared to no change in the omega‐3 ethyl‐ester group (median % change [interquartile range], 5.0% [−5.7, 20.0] versus −0.1% [−12.3, 14.5], respectively; P=0.018). Among those on low‐intensity statins, omega‐3 ethyl‐ester subjects had attenuation of fibrous plaque progression compared to controls (median % change [interquartile range], 0.3% [−12.8, 9.0] versus 4.8% [−5.1, 19.0], respectively; P=0.032). In contrast, those on high‐intensity statins had no difference in plaque change in either treatment arm.ConclusionsHigh‐dose eicosapentaenoic acid and docosahexaenoic acid provided additional benefit to statins in preventing progression of fibrous coronary plaque in subjects adherent to therapy with well‐controlled low‐density lipoprotein cholesterol levels. The benefit on low‐intensity statin, but not high‐intensity statin, suggests that statin intensity affects plaque volume.Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01624727.

Level of DBP predicts coronary plaque with a DBP tertile ≤68 mmHg associated with the least amount of coronary plaque in subjects with LDL-C < 80 mg/dL.

Introduction: Hypertension is a major risk factor for coronary artery disease (CAD) and is associated with increased morbidity and mortality. The effect of systolic vs. diastolic blood pressure (BP) on coronary plaque volume has not been reported. Coronary blood flow occurs during diastole; shear stress affects plaque formation. Hypothesis: Diastolic BP may be a better predictor of plaque volume than systolic BP. Methods: 285 subjects with stable CAD underwent coronary computed tomographic angiography to assess the indexed volume (plaque volume [mm3] divided by segment length [mm]) of fatty, fibrous, non-calcified, calcified and total coronary plaque. Segments with significant calcium-blooming artifact were excluded. A backward linear regression model adjusted for age, gender, BMI, estimated glomerular filtration rate, total cholesterol, LDL-C, HDL-C and triglycerides. Results: Mean (SD) age was 63.1 ± 7.7 years (18% female). A significant increase was observed in volume of all plaque components across diastolic BP tertiles except for calcified which was borderline (p= 0.069) (Table). In contrast, there was no difference in systolic tertiles. In multivariate regression, diastolic BP tertile was a significant independent predictor of volume of all plaque components - fatty (β= 0.075; p=0.038), fibrous (β= 0.178; p= 0.004), non-calcified (β= 0.256; p= 0.008), calcified (β= 0.081; p= 0.007) and total (β= 0.353; p= 0.002) whereas no association was observed between systolic BP tertile and volume of any plaque component (Table). Conclusion: In patients with CAD, diastolic BP tertile independently predicts coronary plaque volume whereas systolic BP tertile does not. Since coronary blood flow occurs during diastole, a possible mechanism for the difference between systolic and diastolic BP is increased shear stress during diastolic blood flow. Therefore, control of diastolic BP may be an important factor in determining plaque volume.