Abstract
ObjectiveAim of this study was to evaluate the relationship of plasma PCSK9 with metabolic and inflammatory profile and coronary atherosclerotic burden in patients with suspected CAD enrolled in the EVINCI study.MethodsPCSK9 was measured in 539 patients (60.3 ± 8.6 years, 256 males) with symptoms of CAD characterized by risk factors, bio-humoral profiles, and treatment. N = 412 patients underwent coronary computed tomography angiography (CTA) to assess the presence and characteristics of coronary atherosclerosis. A CTA score, combining extent, severity, composition, and location of plaques was computed.ResultsPatients were divided according to PCSK9 quartiles: I (< 136 ng/mL), II–III (136–266 ng/mL), and IV quartile (> 266 ng/mL). Compared with patients in quartile IV, patients in quartile I had a higher prevalence of the metabolic syndrome and higher values of body mass index. LDL- and HDL-cholesterol were significantly lower in patients in the quartile I than in those in quartile IV. Coronary CTA documented normal vessels in 30% and obstructive CAD in 35% of cases without differences among PCSK9 quartiles. Compared with patients with the highest levels, patients with the lowest PCSK9 levels had a higher CTA score mainly due to higher number of mixed non-obstructive coronary plaques. At multivariable analysis including clinical, medications, and lipid variables, PCSK9 was an independent predictor of the CTA score (coefficient − 0.129, SE 0.03, P < 0.0001), together with age, male gender, statins, interleukin-6, and leptin.ConclusionIn patients with stable CAD, low PCSK9 plasma levels are associated with a particular metabolic phenotype (low HDL cholesterol, the metabolic syndrome, obesity, insulin resistance and diabetes) and diffuse non-obstructive coronary atherosclerosis.Trial registration ClinicalTrials.gov NCT00979199. Registered September 17, 2009
Highlights
Cardiovascular disease accounts for the largest proportion of deaths in Western countries [1]
We found a relationship of low Proprotein convertase subtilisin/kexin type 9 (PCSK9) levels with insulin resistance or diabetes, obesity or metabolic syndrome
We found no association between PCSK9 and some components of the metabolic syndrome such as triglycerides and hypertension, while we found a very strong association between low PCSK9 levels and high-density lipoprotein (HDL) cholesterol levels, independent of statin use
Summary
Cardiovascular disease accounts for the largest proportion of deaths in Western countries [1]. Most studies exploring the association between plasma PCSK9 and early coronary atherosclerosis demonstrated a not clear direct relationship [11,12,13,14,15,16,17,18] Both the clinical presentation of coronary artery disease (CAD) is changing over time and some risk factors such as obesity, diabetes and metabolic syndrome are emerging as major disease determinants in current populations [19, 20]. There are only few clinical studies evaluating the relationships between circulating levels of PCSK9, other circulating determinants of the atherosclerotic risk and a comprehensive description of coronary artery disease (CAD) phenotype [18]. Studies in this area may be useful to gain new insights on regulatory mechanisms of PCSK9 expression and its effects on CAD in contemporary populations
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