Computed tomography angiography defined vulnerable plaque in a patient with low high-density lipoprotein cholesterol and subsequent myocardial infarction

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Low levels of circulating high-density lipoprotein cholesterol (HDL-C) in asymptomatic patients represent a common and clinically challenging problem. We report a case of a 44-year-old man who experienced an ST-elevation myocardial infarction at the anterior wall in 2014; he was a smoker, sedentary, and heterozygous for a stop codon mutation leading to deficiency in apolipoprotein A-I (apoA-I), with decreased levels of HDL-C. In 2005, he was initially evaluated at our center as a member of a family with two documented homozygotes and eight additional heterozygotes for a mutation at codon-2, Q[-2]X in the APOA1 gene. The homozygotes presented with markedly decreased HDL-C, undetectable plasma apoA-I, tuboeruptive and planar xanthomas, mild corneal arcus and opacification, and severe premature coronary artery disease (CAD) 1. Conversely, all heterozygous patients were asymptomatic. The patient who we describe here had low HDL-C (19 mg/dl), low apoA-I (67 mg/dl), normal low-density lipoprotein-cholesterol (LDL-C; 120 mg/dl), and elevated triglyceride (324 mg/dl) levels. Moreover, ultracentrifugally isolated HDL subpopulations from this patient showed diminished cholesterol efflux capacity (−25%) and antioxidative activity (−48%) compared with age-matched and sex-matched controls 2. Anatomical analysis showed that this patient had only nonobstructive coronary atherosclerosis on computed tomography angiography (CTA) along with a coronary artery calcium score of zero (Fig. 1). Notably, 64-row CTA identified a noncalcific soft atherosclerotic plaque at the proximal segment of the left anterior descending (LAD) artery that resulted in only mild narrowing. We retrospectively evaluated tissue and plaque characteristics (QAngio CT RE 2.1; Medis Medical Imaging Systems, Leiden, the Netherlands) using a novel, research-dedicated, postprocessing software based on automated Housefield unit (HU) thresholding analysis 3. The tissue characterization showed a large lipid-rich necrotic core abutting the lumen suggestive of a thin-cap fibroatheroma, indicating vulnerable plaque. Nine years later, the coronary angiography showed a severely stenotic and ruptured plaque in the LAD at the site of the previous CTA lesion.
The patient had moderately low HDL-C levels mostly because of his heterozygosis for an APOA1 genetic deficiency. Extremely low levels of HDL-C, as found in the homozygotes of this family, are very rare and responsible for severe premature CAD. However, the finding of moderately low levels of HDL-C is not uncommon in heterozygotes. Here, we would like to discuss the prevention and management of cardiovascular disease in this patient with low levels of HDL-C and normal levels of LDL-C.
The intense interest in HDL-raising therapies is underpinned by an impressive body of epidemiological and basic research that has suggested a cardioprotective effect of HDL. Despite strong evidence showing that low HDL-C levels predict cardiovascular events across multiple populations, including patients aggressively treated for LDL-C, efforts to therapeutically target HDL-C have not yet translated into cardiovascular risk reduction. Four orally administered HDL-C-raising drugs, three cholesteryl ester transfer protein inhibitors, and niacin, in combination with statin therapy, failed in prospective intervention trials 4–7. Nonetheless, the residual risk of high-risk patients, despite statin treatment, and the complexity of HDL, explain the continuing efforts of scientific community to develop novel therapies focusing on HDL, including HDL infusion formulations and other agents with the potential to increase HDL function and HDL particles 8. Indeed, the use of HDL-C as the key metric for monitoring the pharmacological modulation of HDL has been questioned, in favor of HDL functionality and HDL particles 9,10. In this present case, the patient not only presented low HDL-C and apoA-I levels but also HDL subpopulations with markedly altered chemical composition and diminished cholesterol efflux capacity and antioxidative activity. Furthermore, he had a noncalcified atherosclerotic plaque in the LAD artery.

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