Lipid-lowering therapy plays a central role in reducing cardiovascular events. Over the past few decades, clinical trials utilizing several imaging techniques have consistently shown that lipid-lowering therapy can reduce the coronary plaque burden and improve plaque composition. Although intravascular ultrasound has been the most extensively used modality to assess plaque burden, other invasive modalities, such as optical coherence tomography and near-infrared spectroscopy, provide relevant data on plaque vulnerability, and computed tomography angiography detects both plaque volume and characteristics non-invasively. A large body of evidence supports the notion that reducing low-density lipoprotein cholesterol using statins combined with ezetimibe and proprotein convertase subtillisin/kexin type 9 inhibitors consistently shows improvements in plaque burden and favorable morphological changes. This review summarizes previously obtained data on the impact of lipid-lowering treatment strategies on atherosclerotic plaque regression, as assessed using several imaging modalities.

BACKGROUND: Elevated Lp(a) (lipoprotein[a]) is a risk marker for atherosclerotic disease, but the underlying mechanisms remain elusive. We examined the association of Lp(a) with changes in coronary atherosclerosis following intensive lipid-lowering therapy. METHODS: In the PACMAN-AMI trial (Effects of the PCSK9 Antibody Alirocumab on Coronary Atherosclerosis in Patients With Acute Myocardial Infarction), 300 patients with acute myocardial infarction were randomized to receive biweekly alirocumab 150 mg or placebo in addition to high-intensity statins. Patients underwent serial 2-vessel intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy in the non–infarct-related arteries at baseline and after 52 weeks. The main end points were percent atheroma volume by intravascular ultrasound, minimum fibrous cap thickness by optical coherence tomography, and maximum lipid core burden index within 4 mm (maxLCBI _4mm ) by near-infrared spectroscopy. RESULTS: A total of 265 patients had serial intravascular ultrasound data (mean age, 58±9 years; 16% women). Alirocumab resulted in greater reductions in percent atheroma volume and maxLCBI _4mm , as well as a greater increase in minimum fibrous cap thickness, compared with placebo. In the alirocumab group, the reduction in maxLCBI _4mm was smaller in patients with higher baseline Lp(a), defined by the highest quartile (Q4, ≥98 nmol/L; n=30), than in those with lower baseline Lp(a) (Q1–Q3, <98 nmol/L; n=99; −40.2 [−91.1 to 10.7] versus −91.4 [−113.9 to −68.9], respectively; P =0.01 after adjustment for clinically relevant baseline variables), and was comparable to the maxLBI _4mm reduction in the placebo group (−37.60 [−57.40 to −17.80]; n=134). These findings were consistent when higher baseline Lp(a) was defined by cut-off values of ≥75 versus <75 nmol/L (n=35 versus 94, respectively, in the alirocumab group) and ≥125 versus <125 nmol/L (n=23 versus 106, respectively). Changes in percent atheroma volume and minimum fibrous cap thickness did not differ in relation to baseline Lp(a). CONCLUSIONS: In patients with acute myocardial infarction, elevated Lp(a) at baseline is associated with attenuation of plaque lipid regression despite intensive treatment with alirocumab plus high-intensity statin. This finding may explain the residual cardiovascular risk associated with high Lp(a) despite optimal control of lipid levels. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03067844.

We evaluated whether underweight status is associated with poor prognosis in patients with peripheral artery disease (PAD) with claudication, excluding critical limb ischemia. We identified 441 claudicants hospitalized for cardiovascular disease between 2005 and 2012. Patients were divided into 4 groups according to body mass index (BMI): an underweight group (BMI < 18.5 kg/m ² ; n = 48), a normal group (BMI = 18.5-25.0 kg/m ² ; n = 286), an overweight group (BMI = 25.0-30.0 kg/m ² ; n = 92), and an obese group (BMI ≥ 30.0 kg/m ² ; n = 15). The mean follow-up period was 3.5 ± 1.9 years. The underweight group had significantly lower levels of hemoglobin, albumin, estimated glomerular filtration rate, triglycerides, and hemoglobin A _1c ; higher levels of C-reactive protein and B-type natriuretic peptide; and a higher prevalence of hemodialysis. The incidence of all-cause death and cardiovascular death was significantly higher in the underweight group (underweight vs normal, 77.1% vs 33.0%; P < .001 and 43.3% vs 14.4%; P < .001, respectively). In a multivariate Cox analysis, underweight status was an independent predictor of all-cause death (hazard ratio, 2.53; 95% confidence interval, 1.58-4.18; P < .001). Therefore, promoting weight gain, as well as managing cardiovascular disease, may be important for underweight patients with PAD.