Inflammation, Lipids Tied to CAD Risk in Psoriasis

Batya Swift Yasgur MA, LSW

September 26, 2018

Novel imaging techniques that assess vascular inflammation (VI) and novel lipid assays are elucidating the association between psoriasis and coronary artery disease (CAD).

Two studies conducted at the National Heart, Lung, and Blood Institute (NHLBI) investigated different ways to assess aortic VI and oxidation-modified lipids (OMLs), which are known drivers of CAD in individuals with psoriasis.

In a study published online September 12 in JAMA Cardiology, Aditya A. Joshi, MD, et al used a combination of imaging techniques to quantify aortic VI and found that it was associated with noncalcified coronary plaque burden (NCB), luminal stenosis, and high-risk plaques (HRP) in patients with psoriasis, suggesting that VI is a surrogate marker for early CAD in this population.

In a study published online September 11 in Circulation Research, Alexander V. Sorokin, MD, PhD, et al investigated the augmentation of traditional lipid parameters with OMLs in the assessment of inflammation in coronary plaques.

OMLs were found to capture the risk for the accumulation of lipid-rich plaque, particularly the NCB, thereby providing an additional clue to the risk for CAD in these patients.

"Both studies show that psoriasis is associated with increased vascular risk, with one study using a nuclear-imaging modality to demonstrate the utility of aortic VI as a reliable surrogate marker for future heart attack and frank CAD," said Nehal N. Mehta, MD, MSCE, chief, Inflammation and Cardiometabolic Diseases, NHLBI, National Institutes of Health, who was senior author of both studies.

The Sorokin study "demonstrated that oxidative stress, commonly seen in this skin disease, actually changed cholesterol and lipoproteins in a way that accelerated atherosclerosis and coronary plaque," he told theheart.org | Medscape Cardiology.

The VI–CAD Connection

"Psoriasis, a chronic inflammatory skin disorder, is associated with heightened cardiovascular risk, increased VI, and increased incidence of early cardiovascular events, including myocardial infarction (MI) and stroke," write Joshi et al.

Aortic VI, determined through fludeoxyglucose F18 positron emission tomography/computed tomography (18F-FDG PET/CT), has been used as a surrogate marker of cardiovascular risk and immune-mediated vascular disease.

"Our previous research using 18F-FDG PET/CT showed that aortic VI was increased in psoriasis and increased the risk of heart attack, but we wanted to know if it would also increase the risk of frank CAD," Mehta said.

The researchers also wanted to investigate the potential utility of coronary computed tomography angiography (CCTA), a technique that "provides qualitative assessment of coronary plaque composition and allows for the volumetric quantification of the burden of CAD while sparing the risks of invasive assessment tools."

NCB, as shown on CCTA, is elevated in psoriasis and associated with thin-cap fibroatheroma that increases the risk for plaque rupture. Moreover, total coronary plaque burden (TB) and NCB are helpful in predicting prospective cardiovascular outcomes.

The researchers used multimodal imaging (18F-FDG PET/CT and CCTA) to analyze the association between aortic VI and CCTA-based quantitative and qualitative CAD indices, including TB and NCB, luminal stenosis, and HRP characteristics.

High Risk for Rupture

The Joshi study involved 215 patients (mean [SD] age, 50.4 [12.6] years; 59% male), with moderate skin disease severity and a median psoriasis duration of 20 years.

Most participants were overweight, with a mean body mass index (BMI) of 29.6 (6.2) kg/m2 and a high prevalence of dyslipidemia (48%), despite near-normal lipid profiles.

Based on atherosclerotic cardiovascular disease 10-year risk calculation, patients with psoriasis were at low risk for cardiovascular disease (CVD); however, at baseline, aortic VI was found to be high.

The quantified TB at baseline was 1.14 (0.44) mm2, which was predominantly composed of NCB (mean [SD], 1.11 [0.46] mm2).

In roughly half the patients, luminal stenosis was greater than 25%, and 57 of 169 patients had prevalent HRP in at least one major epicardial coronary artery.

All patients underwent 18F-FDG PET/CT scans, but only 190 underwent CCTA scans.

Patients with had higher target-to-background ratio (TBR; median, 1.66) vs lower TBR were predominantly male, had higher BMI, lower high-density lipoprotein (HDL) cholesterol, and increased CVD risk.

Comparing the CCTA-based characteristics between patients with higher vs those with lower TBR found that quantitative TB was increased in patients with higher TBR (mean [SD], 1.33 [0.47] vs 0.97 [0.39]; P < .001), which was predominantly driven by NCB (mean [SD], 1.30 [0.47] vs 0.93 [0.37]; < .001).

Additionally, HRP prevalence was higher in those with higher TBR (42% vs 26%; P = .02), driven by the difference in low-attenuation plaque (LAP) score (odds ratio [OR], 5.63; 95% confidence interval [CI], 1.96 - 16.19; P = .001).

Patients with increased aortic VI were found to have increased TB (standardized β = 0.48; P < .001) and a higher prevalence of luminal stenosis (OR, 3.63; 95% CI, 1.71 - 7.70; P = .001) and HRP (OR, 3.05; 95% CI, 1.42 - 6.47; P = .004).

The aortic VI and TB association was primarily driven by NCB (β = 0.49; < .001), whereas the association between aortic VI and HRP was driven by LAP.

All associations of aortic VI remained significant after adjustment for cardiovascular risk factors (age, sex, BMI, diabetes, hypertension, smoking, hyperlipidemia, statin therapy, high-sensitivity C-reactive protein, and psoriasis treatment with systemic/biologic agents): aortic VI and TB (β = 0.23; P < .001), NCB (β = 0.24; < .001), luminal stenosis (OR, 3.40; 95% CI, 1.40 - 8.24; P = .007), and HRP (OR, 2.72; 95% CI, 1.08 - 6.83; = .03).

There was no association observed between aortic VI and dense-calcified coronary plaque burden.

"We found that people with psoriasis who had increased VI not only had more CAD, but also higher-risk coronary plaque that is ready to rupture," Mehta reported.

Oxidative Stress

Sorokin et al examined the types of lipids in patients with psoriasis and their potential contribution to coronary plaques and CVD.

They studied psoriasis patients with moderate skin disease (n = 232; mean [SD] age, 50.13 [12.64] years; 58% male) whose Framingham risk score indicated that they were at low cardiovascular risk (median [IQR], 4.02; [1 -6]).

Subjects with psoriasis were then compared to healthy volunteers (HV).

Almost half of the psoriasis cohort (45%) had been diagnosed with hyperlipidemia and, among them, 68% were on lipid-lowering treatment.

The psoriasis patients and control subjects were profiled for oxidation-modified low-density lipoprotein (oxLDL), oxidation-modified HDL (oxHDL), lipoprotein(a) (Lp[a]), oxidized Lp(a), cholesterol efflux capacity, lipoprotein particle size and number by NMR spectroscopy and paraoxonase (PON1) activity.

Compared with HVs, patients with psoriasis were older and had increased BMI and homeostatic model assessment of insulin resistance (HOMA-IR).

Subjects with psoriasis had increased in Lp(a) and oxHDL (P < .05 for all) with significant association of oxLDL (β = 0.10, = .020) and oxHDL (β = –0.11; = .007) with NCB.

Subjects with psoriasis also expressed significantly higher PON1 (kU/μL) activity compared with HVs (8.55 ± 3.21 vs 6.24 ± 3.82; = .01).

High-sensitivity C-reactive protein (hsCRP) was found to be higher in the psoriasis cohort than in the HVs (median [IQR], 4.48 [0.80 - 4.22] vs1.24 [0.60 - 1.00], = .002).

The researchers followed biologic-naïve psoriasis patients with moderate to severe illness who initiated biologic treatment during the study period and observed a statistically significant increase in TG along with increasing trend in Lp(a) compared with baseline, along with a decrease in oxHDL (203.79 ± 88.40 vs 116.36 ± 85.03; = .0005) at 3- to 5-month follow-up.

At 1-year follow-up, there was a reduction in TB (mean [SD], 1.09 [0.40] vs 1.00 [0.31]; = .01), primarily driven by a reduction in NCB (mean [SD], 1.04 [0.44] vs 0.95 [0.32]; = .03).

"You have to wonder why a skin disease like psoriasis would impact the coronary arteries," Mehta mused.

"The purpose of the study that appeared in Circulation was to demonstrate that the oxidative stress seen in the skin disease actually changes cholesterol and lipoproteins in a way that accelerates atherosclerosis," he said.

"This paper looked at the same patients and asked whether or not they have oxidative-modified lipids and the answer was yes, and whether these oxidative-modified lipids increased coronary plaque, and they did," he summarized.

Earlier Evaluation of Lipids

An editorial accompanying the study by Joshi et al commends the study's methodology, stating, "An imaging tool capable of providing information on the presence and extent of inflammation within vascular walls has a potential translational value, because inflammation contributes to the initiation, progression, and adverse outcomes of atherosclerosis."

The same research tools could have utility not only in psoriasis, but also in other autoimmune diseases and in multifactorial atherosclerosis, they suggest.

Commenting for theheart.org | Medscape Cardiology, Thomas McCormick, PhD, associate professor, Department of Dermatology, Case Western Reserve University, University Hospitals Cleveland Medical Center, who was not involved with the studies, call them "nicely complementary," and "elegant demonstrations of the usefulness of enhanced technologies to monitor surrogate markers for risk of developing atherosclerosis and cardiovascular disease in patients with chronic inflammation brought about by the autoimmune condition psoriasis."

The study of VI "demonstrates the correlative value of FDG-PET/CT imaging with CCTA, offering evidence that the extent of aortic VI predicts plaque burden quantified by CAD imaging," he said.

The study of lipids "takes advantage of the same CCTA technology and combines it with advanced measurements of oxidation-modified lipids to demonstrate the correlation among oxidized lipid moieties and coronary plaque status among psoriasis patients, compared with healthy controls."

"A crucial message for clinicians treating psoriasis patients is that relatively young patients already have increased clinical symptoms for advanced CAD, which places them at a higher risk for eventual cardiovascular failure," McCormick said.

Mehta agreed.

"Clinicians should consider lipid screening for patients with psoriasis earlier than they normally would in patients without psoriasis," he said.

The studies were supported by National Heart, Lung, and Blood Institute Intramural Research Program and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Mehta is a full-time US government employee and receives research grants to the National Heart, Lung, and Blood Institute from AbbVie, Janssen, Celgene, and Novartis. The other authors' disclosures are listed on the original papers. McCormick reveals no relevant conflicts of interest.

Circ Res. Published online September 11, 2018. Sorokin abstract

JAMA Cardiol. Published online September 12, 2018. Joshi abstract, Editorial

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