Complex association of apolipoprotein E-containing HDL with coronary artery disease burden in cardiovascular disease.

BackgroundAlthough traditional lipid parameters and coronary imaging techniques are valuable for cardiovascular disease (CVD) risk prediction, better diagnostic tests are still needed.MethodsIn a prospective, observational study, 795 individuals had extensive cardiometabolic profiling, including emerging biomarkers, such as apolipoprotein E-containing HDL-cholesterol (ApoE-HDL-C). Coronary artery calcium (CAC) score was assessed in the entire cohort, and quantitative coronary computed tomography angiography (CCTA) characterization of total burden, noncalcified burden (NCB), and fibrous plaque burden (FB) was performed in a subcohort (n = 300) of patients stratified by concentration of ApoE-HDL-C. Total and HDL-containing apolipoprotein C-III (ApoC-III) were also measured.ResultsMost patients had a clinical diagnosis of coronary artery disease (CAD) (n = 80.4% of 795), with mean age of 59 years, a majority being male (57%), and about half on statin treatment. The low ApoE-HDL-C group had more severe stenosis (11% vs. 2%, overall P < 0.001), with higher CAC as compared with high ApoE-HDL-C. On quantitative CCTA, the high ApoE-HDL-C group had lower NCB (ß = -0.24, P = 0.0001), which tended to be significant in a fully adjusted model (ß = -0.32, P = 0.001) and altered by ApoC-III in HDL levels. Low ApoE-HDL-C was significantly associated with LDL particle number (ß = 0.31; P = 0.0001). Finally, when stratified by FB, ApoC-III in HDL showed a more robust predictive value of CAD over ApoE-HDL-C (AUC: 0.705, P = 0.0001) in a fully adjusted model.ConclusionApoE-containing HDL-C showed a significant association with early coronary plaque characteristics and is affected by the presence of ApoC-III, indicating that low ApoE-HDL-C and high ApoC-III may be important markers of CVD severity.Trial RegistrationClinicalTrials.gov: NCT01621594.FundingThis work was supported by the NHLBI at the NIH Intramural Research Program.

Nutritional Supplements for the Treatment of Neuropathic Pain.

Neuropathic pain affects 7-10% of the population and is often ineffectively and incompletely treated. Although the gold standard for treatment of neuropathic pain includes tricyclic antidepressants (TCAs), serotonin-noradrenaline reuptake inhibitors, and anticonvulsants, patients suffering from neuropathic pain are increasingly turning to nonpharmacologic treatments, including nutritional supplements for analgesia. So-called "nutraceuticals" have garnered significant interest among patients seeking to self-treat their neuropathic pain with readily available supplements. The supplements most often used by patients include vitamins such as vitamin B and vitamin D, trace minerals zinc and magnesium, and herbal remedies such as curcumin and St. John's Wort. However, evidence surrounding the efficacy and mechanisms of these supplements in neuropathic pain is limited, and the scientific literature consists primarily of preclinical animal models, case studies, and small randomized controlled trials (RCTs). Further exploration into large randomized controlled trials is needed to fully inform patients and physicians on the utility of these supplements in neuropathic pain. In this review, we explore the basis behind using several nutritional supplements commonly used by patients with neuropathic pain seen in rheumatology clinics.

Metabolic syndrome and its factors are associated with noncalcified coronary burden in psoriasis: An observational cohort study.

BACKGROUND: Psoriasis is associated with a heightened risk of cardiovascular disease and higher prevalence of metabolic syndrome. OBJECTIVE: Investigate the effect of metabolic syndrome and its factors on early coronary artery disease assessed as noncalcified coronary burden by coronary computed tomography angiography in psoriasis. METHODS: This cross-sectional study consisted of 260 participants with psoriasis and coronary computed tomography angiography characterization. Metabolic syndrome was defined according to the harmonized International Diabetes Federation criteria. RESULTS: Of the 260 participants, 80 had metabolic syndrome (31%). The metabolic syndrome group had a higher burden of cardiometabolic disease, systemic inflammation, noncalcified coronary burden, and high-risk coronary plaque. After adjusting for Framingham risk score, lipid-lowering therapy, and biologic use, metabolic syndrome (ß = .31; P < .001) and its individual factors of waist circumference (ß = .33; P < .001), triglyceride levels (ß = .17; P = .005), blood pressure (ß = .18; P = .005), and fasting glucose (ß = .17; P = .009) were significantly associated with noncalcified coronary burden. After adjusting for all other metabolic syndrome factors, blood pressure and waist circumference remained significantly associated with noncalcified coronary burden. LIMITATIONS: Observational nature with limited ability to control for confounders. CONCLUSIONS: In psoriasis, individuals with metabolic syndrome had more cardiovascular disease risk factors, systemic inflammation, and noncalcified coronary burden. Efforts to increase metabolic syndrome awareness in psoriasis should be undertaken to reduce the heightened cardiovascular disease risk.

Association Among Noncalcified Coronary Burden, Fractional Flow Reserve, and Myocardial Injury in Psoriasis.

Background Myocardial infarction and premature death have been observed in patients with psoriasis. Although inflammation-driven accelerated atherosclerosis has been proposed as a mechanism, the relationship between subclinical noncalcified coronary burden (NCB), functional coronary flow impairment, and myocardial injury is unclear. Methods and Results In an ongoing longitudinal cohort study, 202 consecutive patients with psoriasis (168 at 1 year) underwent coronary computed tomography angiography to identify coronary plaque, quantify NCB, and calculate coronary fractional flow reserve by computed tomography. Serum high-sensitivity troponin-T (hs-cTn-T) was measured using a fifth-generation assay. Overall, patients were middle-aged, predominantly male, and low cardiovascular risk. A higher than median NCB associated with a positive hs-cTn-T (fully adjusted model [odds ratio (OR), 1.72; 95% CI, 1.10-2.69, P=0.018]) at baseline. Additionally, patients with a higher than median baseline NCB had higher odds of positive hs-cTn-T at 1 year in fully adjusted analyses (adjusted OR, 2.36; 95% CI, 1.47-3.79, P<0.001). Higher NCB was associated with a higher frequency of fractional flow reserve by computed tomography ≤0.80 (36.11% versus 25.11%, Pearson χ2=6.84, P=0.009, unadjusted OR, 2.09; 95% CI, 1.36-3.22, P<0.001) and higher frequency of a positive hs-cTn-T (54.36% versus 27.54%, Pearson χ2=32.23, P<0.001) in adjusted models (OR, 2.63; 95% CI, 1.56-4.42, P<0.001). Conclusions NCB was associated with hs-cTn-T at baseline as well as at 1 year. Furthermore, patients with high NCB had higher prevalence of fractional flow reserve by computed tomography ≤0.80 and a >2- fold higher odds of positive hs-cTn-T. These findings underscore the importance of early vascular disease in driving myocardial injury, and support conduct of myocardial perfusion studies to better understand these findings.

Chronic inflammation in psoriasis promotes visceral adiposity associated with noncalcified coronary burden over time.

BACKGROUNDPsoriasis is a chronic inflammatory skin disease associated with increased obesity, noncalcified coronary artery burden (NCB), and incident myocardial infarction. Here, we sought to assess the relationship among inflammation, visceral adipose tissue (VAT), and NCB. Furthermore, we evaluated whether improvement in VAT would be associated with reduction in NCB over time in psoriasis.METHODSConsecutive psoriasis patients underwent coronary CT angiography to quantify NCB and abdominal CT to calculate VAT at baseline (n = 237), 1 year (n = 176), and 4 years (n = 50).RESULTSPatients with high levels of high-sensitivity C-reactive protein (hs-CRP) had significantly greater visceral adiposity (17,952.9 ± 849.2 cc3 vs. 13370.7 ± 806.8 cc3, P < 0.001) and noncalcified coronary burden (1.26 ± 0.03 vs. 1.07 ± 0.02 mm2) than those with low levels of hs-CRP. Those with higher levels of VAT had more systemic inflammation (hs-CRP, median [IQR], 2.5 mg/L [1.0-5.3 mg/L] vs. 1.2 mg/L [0.6-2.9 mg/L]), with approximately 50% higher NCB (1.42 ± 0.6 mm2 vs. 0.91 ± 0.2 mm2, P < 0.001). VAT associated with NCB in fully adjusted models (ß = 0.47, P < 0.001). At 1-year follow-up, patients who had worsening hs-CRP had an increase in VAT (14,748.7 ± 878.1 cc3 to 15,158.7 ± 881.5 cc3; P = 0.03), whereas those who had improved hs-CRP improved their VAT (16,876.1 ± 915.2 cc3 to 16310.4 ± 889.6 cc3; P = 0.04). At 1 year, there was 10.3% reduction in NCB in those who had decreased VAT (ß = 0.26, P < 0.0001), which persisted in a subset of patients at 4 years (ß = 0.39, P = 0.003).CONCLUSIONSInflammation drives development of VAT, increased cardiometabolic risk, and NCB in psoriasis. Reduction of inflammation associated with reduction in VAT and associated with longitudinal improvement in NCB. These findings demonstrate the important role of inflammation in the development of VAT in humans and its effect on early atherogenesis.TRIAL REGISTRATIONClinicalTrials.gov NCT01778569.FUNDINGThis study was supported by the National Heart, Lung, and Blood Institute Intramural Research Program (HL006193-05), the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation (no. 2014194), the American Association for Dental Research, the Colgate-Palmolive Company, Genentech, and Elsevier as well as private donors.

Treatment of Psoriasis With Biologic Therapy Is Associated With Improvement of Coronary Artery Plaque Lipid-Rich Necrotic Core: Results From a Prospective, Observational Study.

BACKGROUND: Lipid-rich necrotic core (LRNC), a high-risk coronary plaque feature assessed by coronary computed tomography angiography, is associated with increased risk of future cardiovascular events in patients with subclinical, nonobstructive coronary artery disease. Psoriasis is a chronic inflammatory condition that is associated with increased prevalence of high-risk coronary plaque and risk of cardiovascular events. This study characterized LRNC in psoriasis and how LRNC modulates in response to biologic therapy. METHODS: Consecutive biologic naïve psoriasis patients (n=209) underwent coronary computed tomography angiography at baseline and 1-year to assess changes in LRNC using a novel histopathologically validated software (vascuCAP Elucid Bioimaging, Boston, MA) before and after biologic therapy over 1 year. RESULTS: Study participants were middle-aged, predominantly male with similar cardiometabolic and psoriasis status between treatment groups. In all participants at baseline, LRNC was associated with Framingham risk score (ß [standardized ß]=0.12 [95% CI, 0.00-0.15]; P=0.045), and psoriasis severity (ß=0.13 [95% CI, 0.01-0.26]; P=0.029). At 1-year, participants receiving biologic therapy had a reduction in LRNC (mm2; 3.12 [1.99-4.66] versus 2.97 [1.84-4.35]; P=0.028), while those who did not receive biologic therapy over 1 year demonstrated no significant change with nominally higher LRNC (3.12 [1.82-4.60] versus 3.34 [2.04-4.74]; P=0.06). The change in LRNC was significant compared with that of the nonbiologic treated group (ΔLRNC, -0.22 mm2 versus 0.14 mm2, P=0.004) and remained significant after adjusting for cardiovascular risk factors and psoriasis severity (ß=-0.09 [95% CI, -0.01 to -0.18]; P=0.033). CONCLUSIONS: LRNC was associated with psoriasis severity and cardiovascular risk factors in psoriasis. Additionally, there was favorable modification of LRNC in those on biologic therapy. This study provides evidence of potential reduction in LRNC with treatment of systemic inflammation. Larger, longer follow-up prospective studies should be conducted to understand how changes in LRNC may translate into a reduction in future cardiovascular events in psoriasis.

Coronary Computed Tomography Angiography From Clinical Uses to Emerging Technologies: JACC State-of-the-Art Review.

Evaluation of coronary artery disease (CAD) using coronary computed tomography angiography (CCTA) has seen a paradigm shift in the last decade. Evidence increasingly supports the clinical utility of CCTA across various stages of CAD, from the detection of early subclinical disease to the assessment of acute chest pain. Additionally, CCTA can be used to noninvasively quantify plaque burden and identify high-risk plaque, aiding in diagnosis, prognosis, and treatment. This is especially important in the evaluation of CAD in immune-driven conditions with increased cardiovascular disease prevalence. Emerging applications of CCTA based on hemodynamic indices and plaque characterization may provide personalized risk assessment, affect disease detection, and further guide therapy. This review provides an update on the evidence, clinical applications, and emerging technologies surrounding CCTA as highlighted at the 2019 National Heart, Lung and Blood Institute CCTA Summit.

Relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease in psoriasis: Findings from a longitudinal observational cohort study.

BACKGROUND AND AIMS: Amygdalar 18F-fluorodeoxyglucose (FDG) uptake represents chronic stress-related neural activity and associates with coronary artery disease by coronary computed tomography angiography (CCTA). Allostatic load score is a multidimensional measure related to chronic physiological stress which incorporates cardiovascular, metabolic and inflammatory indices. To better understand the relationship between chronic stress-related neural activity, physiological dysregulation and coronary artery disease, we studied the association between amygdalar FDG uptake, allostatic load score and subclinical non-calcified coronary artery burden (NCB) in psoriasis. METHODS: Consecutive psoriasis patients (n = 275 at baseline and n = 205 at one-year follow-up) underwent CCTA for assessment of NCB (QAngio, Medis). Amygdalar FDG uptake and allostatic load score were determined using established methods. RESULTS: Psoriasis patients were middle-aged, predominantly male and white, with low cardiovascular risk by Framingham risk score and moderate-severe psoriasis severity. Allostatic load score associated with psoriasis severity (ß = 0.17, p = 0.01), GlycA (a systemic marker of inflammation, ß = 0.49, p < 0.001), amygdalar activity (ß = 0.30, p < 0.001), and NCB (ß = 0.39; p < 0.001). Moreover, NCB associated with amygdalar activity in participants with high allostatic load score (ß = 0.27; p < 0.001) but not in those with low allostatic load score (ß = 0.07; p = 0.34). Finally, in patients with an improvement in allostatic load score at one year, there was an 8% reduction in amygdalar FDG uptake (p < 0.001) and a 6% reduction in NCB (p = 0.02). CONCLUSIONS: In psoriasis, allostatic load score represents physiological dysregulation and may capture pathways by which chronic stress-related neural activity associates with coronary artery disease, emphasizing the need to further study stress-induced physiological dysregulation in inflammatory disease states.