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1.  Characterization of Lipid Composition and High-Density Lipoprotein Function in HIV-Infected Individuals on Stable Antiretroviral Regimens 
Abstract
There is an increase in the cardiovascular disease (CVD) morbidity in individuals infected with HIV that may be due to inflammatory lipid modulation not captured by traditional lipid measures. The objective of this study was to perform advanced lipoprotein phenotyping inclusive of the high-density lipoprotein (HDL) cholesterol efflux capacity and lipoprotein particle concentration and size in a well-phenotyped group of 118 patients infected with HIV. We used simple and multivariable analyses to determine the associations between advanced lipoprotein parameters and known cardiometabolic risk factors. Participants were on stable antiretroviral therapy (ART) and had benign traditional lipid panels [median total cholesterol, low-density lipoprotein (LDL)-C, HDL-C, and triglycerides of 178 mg/dl, 108 mg/dl, 44 mg/dl, and 122.5 mg/dl, respectively]. However, advanced lipoprotein phenotyping demonstrated an elevation of LDL particle number (median of 1,233 nmol/liter) and a decrease in LDL size (median of 20.4 nm), along with a decrease in protective, large HDL particles (median of 3.15 μmol/liter) and reduced HDL cholesterol efflux capacity in comparison to controls of other studies. HDL cholesterol efflux capacity was associated with HDL levels (β=0.395, p<0.001), small LDL particle concentration (β=–0.198, p=0.031), insulin sensitivity by the Matsuda index (β=0.218, p=0.029), and the Framingham Risk Score (β=–0.184, p=0.046). We demonstrate an atherogenic lipoprotein profile by NMR spectroscopy and HDL efflux measurement in a group of HIV-infected patients on stable ART with normal lipid panels.
doi:10.1089/aid.2014.0239
PMCID: PMC4313425  PMID: 25416403
2.  IL-17A production in human psoriatic blood and lesions by CD146+ T Cells 
doi:10.1038/jid.2014.317
PMCID: PMC4267954  PMID: 25058615
CD146; Psoriasis; Th17; Tc17; Inflammation
5.  Quantification of Atherosclerotic Plaque Activity and Vascular Inflammation using [18-F] Fluorodeoxyglucose Positron Emission Tomography (PET)/Computed Tomography (CT) 
Conventional non-invasive imaging modalities of atherosclerosis such as coronary artery calcium (CAC)1 and carotid intimal medial thickness (C-IMT)2 provide information about the burden of disease. However, despite multiple validation studies of CAC3–5, and C-IMT2,6, these modalities do not accurately assess plaque characteristics7,8, and the composition and inflammatory state of the plaque determine its stability and, therefore, the risk of clinical events9–13.
[18F]-2-fluoro-2-deoxy-D-glucose (FDG) imaging using positron-emission tomography (PET)/computed tomography (CT) has been extensively studied in oncologic metabolism14,15. Studies using animal models and immunohistochemistry in humans show that FDG-PET/CT is exquisitely sensitive for detecting macrophage activity16, an important source of cellular inflammation in vessel walls. More recently, we17,18 and others have shown that FDG-PET/CT enables highly precise, novel measurements of inflammatory activity of activity of atherosclerotic plaques in large and medium-sized arteries9,16,19,20. FDG-PET/CT studies have many advantages over other imaging modalities: 1) high contrast resolution; 2) quantification of plaque volume and metabolic activity allowing for multi-modal atherosclerotic plaque quantification; 3) dynamic, real-time, in vivo imaging; 4) minimal operator dependence. Finally, vascular inflammation detected by FDG-PET/CT has been shown to predict cardiovascular (CV) events independent of traditional risk factors21,22 and is also highly associated with overall burden of atherosclerosis23. Plaque activity by FDG-PET/CT is modulated by known beneficial CV interventions such as short term (12 week) statin therapy24 as well as longer term therapeutic lifestyle changes (16 months)25.
The current methodology for quantification of FDG uptake in atherosclerotic plaque involves measurement of the standardized uptake value (SUV) of an artery of interest and of the venous blood pool in order to calculate a target to background ratio (TBR), which is calculated by dividing the arterial SUV by the venous blood pool SUV. This method has shown to represent a stable, reproducible phenotype over time, has a high sensitivity for detection of vascular inflammation, and also has high inter-and intra-reader reliability26. Here we present our methodology for patient preparation, image acquisition, and quantification of atherosclerotic plaque activity and vascular inflammation using SUV, TBR, and a global parameter called the metabolic volumetric product (MVP). These approaches may be applied to assess vascular inflammation in various study samples of interest in a consistent fashion as we have shown in several prior publications9,20,27,28
doi:10.3791/3777
PMCID: PMC3466935  PMID: 22588186
FDG-PET/CT; atherosclerosis; vascular inflammation; quantitative radiology
6.  Endothelial Cell‐, Platelet‐, and Monocyte/Macrophage‐Derived Microparticles are Elevated in Psoriasis Beyond Cardiometabolic Risk Factors 
Background
Psoriasis, especially when severe, is a risk factor for cardiometabolic disease beyond traditional risk factors. The mechanism of atherogenesis in psoriasis remains unknown. Cell membrane vesicles (ie, microparticles), released upon cell activation or apoptosis, have recently been associated with cardiometabolic disease and may play a pathogenic role. Microparticle levels, particularly from endothelial cells and platelets, are elevated in patients with cardiovascular disorders, metabolic syndrome, other inflammatory diseases, autoimmune conditions, and have been shown to be predictive of cardiovascular outcomes.
Methods and Results
Concentrations of microparticles with positive expression for any of 7 cell surface markers (Annexin V, CD3, CD31, CD41a, CD64, CD105, and CD144) were measured in blood samples from psoriasis patients (n=53) and control subjects without psoriasis (n=41). Platelet‐free plasma was separated from whole blood by one‐step centrifugation for microparticle analysis. Microparticles were fluorescently labeled and characterized by flow cytometry. Higher concentrations of CD105 (5.5/μL versus 2.5/μL, P<0.001), CD31 (31/μL versus 18/μL, P=0.002), CD41a (50/μL versus 22/μL, P<0.001), and CD64 (5.0/μL versus 4.1/μL, P=0.02) singly positive microparticles corresponding to endothelial cell‐, platelet‐, and monocyte/macrophage‐derived microparticles, respectively, were found in psoriasis patients compared with controls. These differences persisted after adjustment for traditional cardiometabolic risk factors including body mass index.
Conclusions
Increased microparticle concentrations, independent of cardiometabolic risk factors, in patients with psoriasis suggest that the presence of increased endothelial cell, platelet, and monocyte/macrophage activation with cell turnover may contribute to the heightened atherogenesis associated with psoriasis.
doi:10.1161/JAHA.113.000507
PMCID: PMC3959700  PMID: 24584739
atherosclerosis; inflammation; microparticles endothelium; platelets; psoriasis; risk factor
7.  A comparison of vascular inflammation in psoriasis, rheumatoid arthritis, and healthy subjects by FDG-PET/CT: a pilot study 
Objective: Psoriasis (PSO) and rheumatoid arthritis (RA) increase cardiovascular diseases (CVD) beyond traditional risk factors. Vascular inflammation has previously been demonstrated to be present in PSO and RA using [18F]-fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) imaging. However, vascular inflammation has not been compared in these two disorders relative to a healthy reference population. Thus, vascular inflammation was quantitatively assessed in patients with PSO (n=10), RA (n=5), and healthy subjects (n=10) using FDG-PET/CT. Methods: FDG-PET/CT mean standardized uptake value (SUVmean) was determined slice by slice within the ascending, aortic arch, descending thoracic, suprarenal abdominal, and infrarenal abdominal aorta, and the mean metabolic volumetric product (MVPmean) was then calculated for each aortic subsegment. Plasma lipids and metabolic and inflammatory markers were also assessed. Results: CVD risk profiles were largely similar across groups. After adjustment for CV risk factors, regional aortic vascular inflammation based on MVPmean was elevated for both PSO (beta coefficients 0.31-1.47, p<0.001) and RA (beta coefficients 0.15-0.69, p<0.05) compared to healthy subjects. Conclusions: These observations using FDG-PET/CT to estimate vascular inflammation support epidemiological findings of premature atherosclerosis in PSO and RA. The use of FDG-PET/CT to investigate vascular inflammation across systemic inflammatory diseases warrants further examination in larger study populations.
PMCID: PMC3819587  PMID: 24224139
Psoriasis; rheumatoid arthritis; atherosclerosis; vascular inflammation; FDG-PET/CT
9.  Abnormal Lipoprotein Particles and Cholesterol Efflux Capacity in Patients with Psoriasis 
Atherosclerosis  2012;224(1):218-221.
Objectives
Psoriasis is a Th-1/17 mediated inflammatory disease associated with increased risk of cardiovascular disease (CVD). Inflammation may modulate lipoprotein particle number and directly impair HDL functions, in particular reverse cholesterol transport (RCT). We sought to study how chronic in vivo inflammation modulates lipoprotein particle composition using nuclear magnetic resonance spectroscopy (NMR) and HDL efflux in psoriasis.
Methods and Results
We prospectively enrolled a consecutive sample of patients with psoriasis (n=122) and compared lipoprotein and metabolic risk factors to patients without psoriasis (n=134). Fasting lipids, insulin, glucose were measured by standard assays, and lipoprotein concentration and size were measured by NMR. In a random subset (n=100 each group), HDL efflux capacity was quantified using a validated ex vivo system involving the incubation of macrophages with apolipoprotein B-depleted serum from patients. Traditional lipid concentrations were similar in both groups except for HDL concentration which was lower in psoriasis (43 mg/dL (36–58) vs 50 (42–62), p<0.01). However, NMR showed an atherogenic profile in psoriasis similar to that observed in diabetes, with significant increase in LDL particle concentration [1210.5 (1002–1498) vs 1115 (935–1291), p=0.03] with decrease in LDL size [20.6 (20.3–21.1) vs 21.3 (20.6–21.1), p<0.001] beyond CV risk factors and HOMA-IR (p=0.001). Finally, HDL efflux capacity was lower in psoriasis compared to controls in fully adjusted models (beta −0.14, p=0.001).
Conclusions
These data support a more atherogenic lipoprotein profile by NMR and decreased HDL efflux capacity in psoriasis patients compared to controls beyond CVD risk factors. The abnormal lipoprotein particle composition and HDL efflux capacity in psoriasis may provide a link between psoriasis and CVD.
doi:10.1016/j.atherosclerosis.2012.06.068
PMCID: PMC3693845  PMID: 22858285
inflammation; atherosclerosis; HDL efflux; cholesterol; lipoprotein particles
10.  Monocyte Mayhem: Do Subtypes Modulate Distinct Atherosclerosis Phenotypes? 
doi:10.1161/CIRCGENETICS.111.962647
PMCID: PMC3670688  PMID: 22337925
editorial; monocytes; cardiovascular outcomes; inflammation
11.  A Genome-Wide Association Study in Europeans and South Asians Identifies Five New Loci for Coronary Artery Disease 
doi:10.1161/CIRCGENETICS.111.960989
PMCID: PMC3190399  PMID: 21846871
genomics; genetics; coronary artery disease; genome wide association; meta-analysis
12.  Fluorescent Green Plaques: Light at the End of the Catheter? 
Cell metabolism  2011;14(1):7-8.
The field of vascular molecular imaging is searching for the `holy grail' of an imaging technique that will quantitatively and reliably assess vulnerable coronary plaques. Fluorescence imaging with indocyanine green specifically identifies lipid-rich plaques in rabbits and in human plaques and represents a promising, though invasive, approach.
doi:10.1016/j.cmet.2011.06.005
PMCID: PMC3138117  PMID: 21723499
13.  Large-Scale Association Analysis Identifies 13 New Susceptibility Loci for Coronary Artery Disease 
doi:10.1161/CIRCGENETICS.111.960443
PMCID: PMC3125595  PMID: 21673312
genomics; genetics; coronary artery disease; genome wide association; metaanalysis
14.  Usefulness of Insulin Resistance Estimation and the Metabolic Syndrome in Predicting Coronary Atherosclerosis in Type 2 Diabetes Mellitus 
The American journal of cardiology  2011;107(3):406-411.
Metabolic syndrome (MS) definitions predict cardiovascular events beyond traditional risk factors in type 2 diabetic (DM) as well as non-diabetics subjects. We and other have shown that apolipoprotein B (apoB) and non-HDL cholesterol (non-HDL-C) are associated with coronary artery calcification (CAC) in DM. However, the relative value of MS, apoB lipoproteins and estimates of insulin resistance is unknown in predicting atherosclerosis in DM. We performed cross sectional analyses of white subjects in 2 community based studies (N= 611 type 2 diabetic subjects, N= 803 non-diabetic subjects) using multivariate analysis of traditional risk factors and then adding MS, apoB and homeostatic model assessment for insulin resistance (HOMA-IR). Incremental value was tested with likelihood ratio testing. Beyond traditional risk, HOMA-IR [Tobit regression ratio 1.86 (p=0.002)], apoB [1.55 (p=0.001)] and MS [2.37 (p=0.007)] were independently associated with CAC. In nested models, HOMA-IR added value to apoB [1.72 (p=0.008)], MS [1.72 (p=0.011)] and both apoB and MS [1.64 (p=0.021)]. ApoB showed a similar pattern when added to HOMA-IR [1.51 (p=0.004)], MS [1.46 (p=0.005)] and both HOMA-IR and MS [1.48 (p=0.006)]. MS added to apoB [1.99 (p=0.032)], but not HOMA-IR [1.54 (p=0.221)] or both apoB and HOMA-IR [1.32 (p=0.434)]. In conclusion, insulin resistance estimates add value to MS and apoB in predicting CAC scores in DM and warrant further evaluation in clinic for identification of DM patients at higher risk for atherosclerotic cardiovascular disease.
doi:10.1016/j.amjcard.2010.09.035
PMCID: PMC3040419  PMID: 21257006
insulin resistance; apolipoprotein B; coronary artery calcification; type 2 diabetes
15.  CXCL12: A New Player in Coronary Disease Identified through Human Genetics 
Trends in cardiovascular medicine  2010;20(6):204-209.
Genome-wide association studies (GWAS) in over 100,000 people have revealed novel loci associated with coronary artery disease (CAD) and myocardial infarction (MI) which present exciting opportunities to discover novel disease pathways. One such recently identified locus is on chromosome 10q11, near the gene for the chemokine CXCL12 which has been implicated in cardiovascular disease (CVD) in both mouse and human studies. These GWAS demonstrate that CXCL12 may emerge as a potential therapeutic target for atherosclerosis and thrombosis.
doi:10.1016/j.tcm.2011.08.002
PMCID: PMC3235407  PMID: 22137643
CXCL12; atherosclerosis; GWAS; cardiovascular disease; inflammation
16.  Systemic and Vascular Inflammation in Patients with Moderate to Severe Psoriasis as measured by [18F]-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (FDG-PET/CT): A Pilot Study 
Archives of dermatology  2011;147(9):1031-1039.
Objective
To evaluate the feasibility of utilizing [18F]-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET/CT) to detect and quantify systemic inflammation in psoriasis patients.
Design
Case series with a nested case-control study.
Setting
Referral dermatology and preventive cardiology practices.
Participants
Six patients with psoriasis affecting >10% body surface area and 4 controls age and sex matched to 4 psoriasis patients for a nested case-control study.
Main Outcome Measures
FDG uptake in the liver, musculoskeletal structures, and aorta measured by mean Standardized Uptake Value (SUV), a measure of FDG tracer uptake by macrophages and other inflammatory cells.
Results
FDG-PET/CT identified numerous foci of inflammation in 6 patients with psoriasis within the skin, liver, joints, tendons, and aorta. Inflammation in the joints was observed in a patient with psoriatic arthritis as well as in 1 patient with no history of joint disease or joint symptoms. In a nested case-control study, FDG-PET/CT imaging demonstrated increased vascular inflammation in multiple segments of the aorta compared to controls. These findings persisted after adjustment for traditional cardiovascular risk factors in multivariate analysis (mean beta 0.33, p<0.001). Patients with psoriasis further demonstrated increased hepatic inflammation after adjusting for cardiovascular risk factors (beta 0.18, p<0.001), but the association was no longer significant when adjusted for alcohol intake (beta −0.25, p=0.07).
Conclusions
FDG-PET/CT is a sensitive tool for identifying inflammation and can be used to identify clinically observed inflammation in the skin and subclinical inflammation in the blood vessels, joints, and liver of patients with psoriasis.
doi:10.1001/archdermatol.2011.119
PMCID: PMC3158301  PMID: 21576552
17.  Attributable Risk Estimate of Severe Psoriasis on Major Cardiovascular Events 
The American journal of medicine  2011;124(8):775.e1-775.e6.
Background
Recent studies suggest that psoriasis, particularly if severe, may be a risk factor for major adverse cardiac events such as myocardial infarction, stroke, and mortality from cardiovascular disease. We compared the risk of major adverse cardiac events between patients with psoriasis and the general population and estimated the attributable risk of severe psoriasis.
Methods
We performed a cohort study in the General Practice Research Database. Severe psoriasis was defined as receiving a psoriasis diagnosis and systemic therapy (N=3,603). Up to 4 patients without psoriasis were selected from the same practices and start dates for each patient with psoriasis (N=14,330).
Results
Severe psoriasis was a risk factor for major adverse cardiac events (hazard ratio 1.53; 95% confidence interval 1.26, 1.85) after adjusting for age, gender, diabetes, hypertension, tobacco use and hyperlipidemia. After fully adjusted analysis, severe psoriasis conferred an additional 6.2% absolute risk of 10-year major adverse cardiac events.
Conclusions
Severe psoriasis confers an additional 6.2% absolute risk of 10-year rate of major adverse cardiac events compared to the general population. This potentially has important therapeutic implications for cardiovascular risk stratification and prevention in patients with severe psoriasis. Future prospective studies are needed to validate these findings.
doi:10.1016/j.amjmed.2011.03.028
PMCID: PMC3146037  PMID: 21787906
Psoriasis; major adverse cardiac events; inflammation; risk factors
18.  Activation of innate immunity modulates insulin sensitivity, glucose effectiveness and pancreatic β-cell function in both African ancestry and European ancestry healthy humans 
Objective
Insulin resistance is a risk factor for type 2 diabetes, and is associated with inflammatory cardiometabolic disease. Given differences between African ancestry (AA) and European ancestry (EA) in the epidemiology of type 2 diabetes as well as in response to inflammatory stress, we investigated potential race differences in glucose homeostasis responses during experimental endotoxemia in humans.
Methods
Healthy volunteers (age 18-45 years, BMI 18-30 kg/m2, 47% female, African-ancestry (AA, n=42) and European-ancestry (EA, n=106)) were recruited as part of the Genetics of Evoked Responses to Niacin and Endotoxemia (GENE) Study. Subjects underwent an inpatient endotoxin challenge (1ng/kg LPS) and two frequently-sampled intravenous glucose tolerance tests (FSIGTT). Insulin and glucose values obtained during FSIGTT pre- and 24-hours post-LPS were analyzed using the minimal model.
Results
FSIGTT derived insulin sensitivity index (SI), disposition index (DI) and glucose effectiveness (SG) decreased significantly following LPS (p<0.0001) while the acute insulin response to glucose (AIRg) increased (p<0.0001). Although expected race differences were observed in glucose homeostasis parameters at baseline prior to LPS e.g., lower SI (2.5 vs. 4.1 μU/L/min, p<0.0001) but higher AIRg (median 848 vs. 290 μU/L/min, p<0.0001) in AA vs. EA, the changes in glucose homeostasis responses to LPS were directionally and proportionally consistent across race e.g., SI median −35% in EA and −29% in AA and AIRg median +17% in EA and +26% in AA.
Conclusion
Both EA and AA samples modulated glucose and insulin homeostasis similarly during endotoxemia.
Implications
Race differences in response to environmental inflammatory stress are unlikely to be a substantial contributor to the observed difference in diabetes incidence and complications between EA and AA.
doi:10.1016/j.metabol.2014.12.007
PMCID: PMC4346476  PMID: 25579865
Insulin sensitivity; Glucose effectiveness; LPS; Race differences
20.  Lipoprotein Concentration, Particle Number, Size and Cholesterol Efflux Capacity are associated with Mitochondrial Oxidative Stress and Function in an HIV Positive Cohort 
Atherosclerosis  2014;239(1):50-54.
Background
Association of lipoprotein particle size/number and HDL function with mitochondrial oxidative stress and function may underlie the excess cardiovascular (CVD) risk in HIV.
Methods and Results
Among HIV infected individuals on stable highly active antiretroviral therapy, we related standard and novel lipid measures [plasma total cholesterol, triglycerides, HDL-C, LDL-C, lipoprotein particle (-P) subclass size and number and HDL function (via cholesterol-efflux capacity)] with oxidative stress [peripheral blood mononuclear cell’s mitochondrial-specific 8-oxo-deoxyguanine (8-oxo-dG)] and function markers [oxidative phosphorylation (OXPHOS) NADH dehydrogenase (Complex I) and cytochrome c oxidase (Complex IV) enzyme activities]. Multivariable-adjusted logistic and linear regression analyses were employed adjusting for age, gender, CD4 nadir, viral load, smoking, diabetes, HOMA-IR, hypertension and lipid medications. Among 150 HIV-infected persons (mean age 52 years, 12% women, median CD4 count 524 cell/mm3), low HDL-C and high total cholesterol/HDL-C ratio were related to PBMC 8-oxo-deoxyguanine (p=0.01 and 0.02 respectively). Large HDL-P and HDL-P size were inversely related to PBMC 8-oxo-deoxyguanine (p=0.04). Small LDL-P (p=0.01) and total LDL-P (p=0.01) were related to decreased OXPHOS Complex I activity. LDL-P was related to decreased OXPHOS Complex IV activity (p=0.02). Cholesterol efflux capacity was associated with increased OXPHOS Complex IV activity.
Conclusions
HDL concentration and particle size and number are related to decreased PBMC mitochondrial oxidative stress whereas HDL function is positively related to mitochondrial oxidative function. The association we find between atherogenic lipoprotein profile and increased oxidative stress and function suggests these pathways may be important in the pathogenesis of cardiometabolic disease in HIV disease.
doi:10.1016/j.atherosclerosis.2014.12.005
PMCID: PMC4370782  PMID: 25574857
atherosclerosis; cardiovascular disease; lipids; NMR spectroscopy; oxidative phosphorylation; cholesterol efflux capacity; HDL
21.  Effect of Psoriasis Severity on Hypertension Control: A Population-Based Study in the United Kingdom 
JAMA dermatology  2015;151(2):161-169.
Importance
Hypertension is prevalent among patients with psoriasis. The effect of psoriasis and its severity on hypertension control is unknown.
Objective
To determine the association between uncontrolled blood pressure and psoriasis, both overall and according to objectively measured psoriasis severity, among patients with diagnosed hypertension.
Design, Setting, and Participants
Population-based cross-sectional study nested in a prospective cohort drawn from The Health Improvement Network (THIN), an electronic medical records database broadly representative of the general population in the United Kingdom. The study population included a random sample of patients with psoriasis (n = 1322) between the ages of 25 and 64 years in THIN who were included in the Incident Health Outcomes and Psoriasis Events prospective cohort and their age- and practice-matched controls without psoriasis (n = 11 977). All included patients had a diagnosis of hypertension; their psoriasis diagnosis was confirmed and disease severity was classified by their general practitioners.
Main outcomes and measures
Uncontrolled hypertension was defined as a systolic blood pressure of 140 mm Hg or higher or a diastolic blood pressure of 90 mm Hg or higher based on the blood pressure recorded closest in time to the assessment of psoriasis severity.
Results
There was a significant positive dose-response relationship between uncontrolled hypertension and psoriasis severity as objectively determined by the affected body surface area in both unadjusted and adjusted analyses that controlled for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs (adjusted odds ratio [aOR], 0.97; 95% CI, 0.82-1.14 for mild psoriasis; aOR, 1.20; 95% CI, 0.99-1.45 for moderate psoriasis; and aOR, 1.48; 95% CI, 1.08-2.04 for severe psoriasis; P = .01 for trend). The likelihood of uncontrolled hypertension among psoriasis overall was also increased, although not statistically significantly so (aOR, 1.10; 95% CI, 0.98-1.24).
Conclusions and Relevance
Among patients with hypertension, psoriasis was associated with a greater likelihood of uncontrolled hypertension in a dose-dependent manner, with the greatest likelihood observed among those with moderate to severe psoriasis defined by 3% or more of the body surface area affected. Our data suggest a need for more effective blood pressure management, particularly among patients with more severe psoriasis.
doi:10.1001/jamadermatol.2014.2094
PMCID: PMC4728300  PMID: 25322196
22.  Accumulating Evidence for the Association and Shared Pathogenic Mechanisms between Psoriasis and Cardiovascular–Related Co-morbidities 
The American journal of medicine  2014;127(12):1148-1153.
The International Psoriasis Council (IPC), a global non-profit organization dedicated to advancing psoriasis research and treatment, led an initiative to better define the association of various cardiometabolic comorbidities with psoriasis. In November 2013, a workshop was held in Boston, MA. By assembling a panel of global dermatology, immunology and cardiovascular experts, the objective was to better define the current status of the science that explains the association of psoriasis with various cardiometabolic-related comorbidities. IPC has played a historical role in associating psoriasis with various comorbidities by integrating multidisciplinary expertise to advance the scientific and clinical knowledge through publications and clinical trials. This report synthesizes the current understanding of psoriasis with various cardiometabolic risk factors by exploring the potential shared pathogenic mechanisms and genetic connectivity.
doi:10.1016/j.amjmed.2014.08.008
PMCID: PMC4259841  PMID: 25149424
cardiovascular; cardiovascular disease; psoriasis; atherosclerosis; inflammation; inflammatory pathway; metabolic syndrome; Il-17
23.  Management of hyperlipidemia among patients with rheumatoid arthritis in the primary care setting 
Background
Rheumatoid arthritis (RA) has been associated with an increased risk of cardiovascular morbidity and mortality but this has not translated to optimal management of traditional cardiovascular risk factors such as hyperlipidemia. The objectives of this study were to 1) determine the prevalence of screening for hyperlipidemia in patients with RA followed by primary care practitioners (PCP); 2) examine initiation of lipid-lowering therapy in patients with an indication, and 3) assess whether proposed modifications to cardiovascular risk calculations change the percentage of RA patients with an indication for therapy.
Methods
We performed a retrospective cohort study using an academic medical center-based medical record database in the United States. Patients with RA defined by the presence of at least one ICD-9 code between 2005–2010 and followed by a PCP within the health care system were included. The positive predictive value of ICD-9 codes for accurately identifying patients with RA was 96.7 %. Descriptive statistics were used to report the prevalence of screening and use of lipid-lowering therapy among those with an indication. Factors associated with not receiving lipid screening were examined using logistic regression models. Indication for and receipt of therapy were then assessed before and after the application of the European Union League Against Rheumatism (EULAR) recommended multiplier to the Framingham risk score.
Results
Among 1,056 patients with RA followed by PCPs and eligible for lipid screening, lipid screening was ordered for 539 (51 %) within the 3-year follow-up period. Patients with diabetes, hypertension, chronic kidney disease, obesity or age >50 were more likely to be screened. Of those with lipid results (N = 290), 25 (9 %) patients had an indication for lipid-lowering therapy based on Adult Treatment Panel III guidelines. Ten (40 %) patients with an indication for lipid-lowering therapy received therapy did not receive therapy. Applying the EULAR multiplier only changed the indication for lipid-lowering therapy in two patients.
Conclusions
Screening and management of traditional cardiovascular risk factors, including hyperlipidemia, need to be optimized.
doi:10.1186/s12891-015-0700-5
PMCID: PMC4559905  PMID: 26336889
24.  Stromal Cell-Derived Factor 1 (SDF-1) as a Biomarker of Heart Failure and Mortality Risk 
Objective
CXCL12 encodes stromal cell-derived factor 1 alpha (SDF-1), which binds to the receptor encoded by CXCR4. Variation at the CXCL12 locus is associated with coronary artery disease (CAD) and endothelial progenitor cell (EPC) numbers, while variation at the CXCR4 locus is associated with leukocyte telomere length (LTL), which has been shown to be associated with CAD. We therefore examined the relations of plasma SDF-1 levels to cardiovascular disease (CVD)-related outcomes, risk factors, LTL, and EPCs.
Approach and Results
SDF-1 was measured in 3359 Framingham Heart Study participants. We used Cox regression to examine relations of SDF-1 to new-onset CVD, myocardial infarction (MI), heart failure (HF), and all-cause mortality; we used linear regression to evaluate associations of SDF-1 with risk factors, LTL, and CD34+ cell phenotypes. In multivariable models, higher SDF-1 levels were associated with older age, lower levels of HDL cholesterol, and cigarette smoking. Higher SDF-1 levels were associated with lower CD34+ cell frequency (p=0.02), but not with LTL. During follow-up (median 9.3 years), there were 263 new-onset CVD events, 160 MIs, 200 HF events, and 385 deaths. After adjusting for clinical risk factors, SDF-1 levels were associated with HF (p=0.04) and all-cause mortality (p=0.003), but not with CVD (p=0.39) or MI (p=0.10). The association of SDF-1 levels with MI was attenuated after adjustment for HDL cholesterol.
Conclusions
After adjusting for traditional CVD risk factors, SDF-1 is associated with HF and all-cause mortality risk. Further studies are needed to determine whether measurement of SDF-1 levels has clinical utility.
doi:10.1161/ATVBAHA.114.303579
PMCID: PMC4142677  PMID: 25060794
Cardiovascular disease; epidemiology; myocardial infarction; heart failure; mortality; stromal cell-derived factor 1; progenitor cells
25.  Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort study 
European Heart Journal  2013;35(31):2115-2122.
Aims
Genome-wide association studies revealed an association between a locus at 10q11, downstream from CXCL12, and myocardial infarction (MI). However, the relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors, incident MI, and death is unknown.
Methods and results
We analysed study-entry plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI or death. Plasma CXCL12 levels were positively associated with several cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia), lower estimated glomerular filtration rate (eGFR), and higher inflammatory cytokine levels (P < 0.05). In fully adjusted models, higher study-entry CXCL12 was associated with increased odds of prevalent CVD (OR 1.23; 95% confidence interval 1.14, 1.33, P < 0.001) for one standard deviation (SD) increase in CXCL12. Similarly, one SD higher CXCL12 increased the hazard of incident MI (1.26; 1.09,1.45, P < 0.001), death (1.20; 1.09,1.33, P < 0.001), and combined MI/death (1.23; 1.13–1.34, P < 0.001) adjusting for demographic factors, known CVD risk factors, and inflammatory markers and remained significant for MI (1.19; 1.03,1.39, P = 0.01) and the combined MI/death (1.13; 1.03,1.24, P = 0.01) after further controlling for eGFR and urinary albumin:creatinine ratio.
Conclusions
In CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death. Further studies are required to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a tool for genomic and therapeutic trials.
doi:10.1093/eurheartj/eht481
PMCID: PMC4132636  PMID: 24306482
Atherosclerosis; Chemokines; Myocardial infarction; CXCL12

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