Article Abstract

Regression of coronary atherosclerosis with lipid-lowering and invasive strategies in Caucasian and East Asian populations: a systematic overview of 38 intravascular ultrasound imaging studies with 9,146 patients

Authors: Alexander N. Kharlamov


The atheroprotective potential of the lipid-lowering and invasive strategies remains disputable. The aim of the study was to estimate racial disparities in these studies. This hypothesis-generating pooled analysis comparatively evaluates baseline characteristics of the coronary anatomy and patterns of the regression of atherosclerosis in Caucasian and East Asian populations (EAP) of the different Y chromosome DNA (Y-DNA) haplogroups in 38 intravascular ultrasound (IVUS) imaging studies (N=9,146). The analysis has revealed 7 so called classic (51.1% of the total analyzed population) studies (conducted by the group of Nicholls/Nissen) with mostly Caucasian population (R1b, Q3, C4 and K4 Y-DNA dominant haplogroups), 18 clinical studies (31.7%) with White/Caucasian population (mostly Europeans of R1 haplogroup), and 13 trials (17.2%) with EAP [11 Japanese studies, 2 South Korean (SK), and 1 Chinese with O and D Y-DNA dominant haplogroups]. The classic trials perform superior with lower mean risk of bias (10.96%) if compare with the rest of Caucasian (21.62%) or EAP (28.88%) studies. The regression of atherosclerosis was documented in 18 of 38 studies. A –1.67%±5.99% means absolute reduction of plaque burden (PB) reported in all 38 studies with a –18.46%±20.35% decrease of low-density lipoprotein (LDL) cholesterol. The Glagovian threshold of a 40% PB with a baseline percent atheroma volume (PAV) above 40% was achieved in one study, a NANOM-FIM trial. The rule “the higher baseline PB the less atheroprotective effect” has been trending with a baseline PB <40.30% (P=0.14) and >65.50% (P=0.39). A pooled linear regression analysis revealed moderate association between LDL-C and PB (r=0.3314, P=0.008) with a LDL-C threshold of 106 mg/dL. The EAP studies substantially differ from Caucasian trials by the smaller size of both lesions and vessels. A baseline total atheroma volume (TAV) in EAP achieved 114.25±80.44 mm3 with a mean total vessel volume (TVV) of 216.31±150.15 mm3 if compare with 185.64±21.75 mm3 (P=0.007) TAV, and a 489.40±48.76 mm3 (P<0.0001) TVV in classic Caucasian trials. Unlike the modest 0.14%±0.94% (P=0.89) progression of atherosclerosis in classic studies (P=0.11) LDL-C reduction, the EAP demonstrate a –1.99%±3.57% (P=0.19) atheroregression amid a mean –31.29%±15.66% (P<0.0001) decrease of LDL-C. So, the relatively tiny size of coronary arteries and high baseline PB in East Asian studies drive the gains in these populations. Regretfully, unlike the invasive strategy, lipid-lowering therapy was not successful enough for regression of atherosclerosis despite substantial reduction of LDL-C. A race with a genetic haplogroup and a level of the per cent atheroma volume must be reckoned for the stages of study preparation and then analysis of the results.


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