Kashif Jafri

Cholesterol Efflux Capacity, High-Density Lipoprotein Function, and Atherosclerosis

BACKGROUND High-density lipoprotein (HDL) may provide cardiovascular protection by promoting reverse cholesterol transport from macrophages. We hypothesized that the capacity of HDL to accept cholesterol from macrophages would serve as a predictor of atherosclerotic burden. METHODS We measured cholesterol efflux capacity in 203 healthy volunteers who underwent assessment of carotid artery intima-media thickness, 442 patients with angiographically confirmed coronary artery disease, and 351 patients without such angiographically confirmed disease. We quantified efflux capacity by using a validated ex vivo system that involved incubation of macrophages with apolipoprotein B-depleted serum from the study participants. RESULTS The levels of HDL cholesterol and apolipoprotein A-I were significant determinants of cholesterol efflux capacity but accounted for less than 40% of the observed variation. An inverse relationship was noted between efflux capacity and carotid intima-media thickness both before and after adjustment for the HDL cholesterol level. Furthermore, efflux capacity was a strong inverse predictor of coronary disease status (adjusted odds ratio for coronary disease per 1-SD increase in efflux capacity, 0.70; 95% confidence interval [CI], 0.59 to 0.83; P<0.001). This relationship was attenuated, but remained significant, after additional adjustment for the HDL cholesterol level (odds ratio per 1-SD increase, 0.75; 95% CI, 0.63 to 0.90; P=0.002) or apolipoprotein A-I level (odds ratio per 1-SD increase, 0.74; 95% CI, 0.61 to 0.89; P=0.002). Additional studies showed enhanced efflux capacity in patients with the metabolic syndrome and low HDL cholesterol levels who were treated with pioglitazone, but not in patients with hypercholesterolemia who were treated with statins. CONCLUSIONS Cholesterol efflux capacity from macrophages, a metric of HDL function, has a strong inverse association with both carotid intima-media thickness and the likelihood of angiographic coronary artery disease, independently of the HDL cholesterol level. (Funded by the National Heart, Lung, and Blood Institute and others.).

The Anti-Oxidative Capacity of High-Density Lipoprotein Is Reduced in Acute Coronary Syndrome But Not in Stable Coronary Artery Disease

OBJECTIVES This study examined an anti-inflammatory property of high-density lipoprotein (HDL) in subjects with acute coronary syndrome (ACS) and stable coronary artery disease (CAD) compared with control subjects. BACKGROUND HDL has anti-inflammatory properties in vitro, but its relationship to coronary disease in humans is unclear. The high-density lipoprotein inflammatory index (HII) measures the ability of HDL to mitigate oxidation of low-density lipoprotein; this function may be impaired in ACS and/or CAD. METHODS We measured HII in 193 patients undergoing angiography for symptoms of CAD. Control subjects (n = 99) had no angiographic CAD, chronic CAD subjects (n = 51) had ≥ 70% vessel stenosis, and ACS subjects (n = 43) had ≥ 20% vessel stenosis and ischemia or infarction. We also examined HII in a cohort of healthy subjects randomly assigned to a statin or placebo. RESULTS Subjects who had ACS had higher HII (less antioxidative capacity) compared with controls (1.57 vs. 1.17, p = 0.005) or those with chronic CAD (1.57 vs. 1.11, p = 0.006). HII was not different in subjects with stable CAD compared with controls. Furthermore, those subjects with higher HII were more likely to have ACS than no CAD (quartile 4 vs. 1, odds ratio [OR]: 1.74, p = 0.008). In a multivariate logistic regression model, HII was associated with ACS after adjusting for traditional cardiac risk factors (OR: 3.8, p = 0.003). There was a small improvement in HII after statin therapy compared with placebo (-14%, p = 0.03). CONCLUSIONS HDL has less anti-inflammatory capacity as assessed by HII in the setting of ACS compared with controls or subjects with chronic CAD.

Incidence and Management of Cardiovascular Risk Factors in Psoriatic Arthritis and Rheumatoid Arthritis: A Population‐Based Study

To examine the prevalence and incidence of cardiovascular (CV) risk factors, including hypertension, hyperlipidemia, diabetes mellitus (DM), and obesity among patients with psoriatic arthritis (PsA) and rheumatoid arthritis (RA) compared to the general population, and to examine the treatment of incident CV risk factors in PsA and RA compared to controls.

Immune Reconstitution Inflammatory Syndrome Associated with Biologic Therapy

The use of biologics in the treatment of autoimmune disease, cancer, and other immune conditions has revolutionized medical care in these areas. However, there are drawbacks to the use of these medications including increased susceptibility to opportunistic infections. One unforeseen risk once opportunistic infection has occurred with biologic use is the onset of immune reconstitution inflammatory syndrome (IRIS) upon drug withdrawal. Although originally described in human immunodeficiency virus (HIV) patients receiving highly active antiretroviral therapy, it has become clear that IRIS may occur when recovery of immune function follows opportunistic infection in the setting of previous immune compromise/suppression. In this review, we draw attention to this potential pitfall on the use of biologic drugs.

Central Nervous System Manifestations of Systemic Lupus Erythematosus

Neuropsychiatric systemic lupus erythematosus (NPSLE) encompasses a variety of phenomena. Manifestations are focal or diffuse, and correlate with disease mechanisms. Recent understanding of the contribution of blood-brain barrier dysfunction to the passage of circulating antineuronal antibodies into the brain parenchyma has shed light on pathogenesis. Correct attribution of neuropsychiatric manifestations to SLE remains a challenge, but validated attribution models will help. Diagnosis relies on characteristic clinical manifestations, SLE disease activity, antibody measurements, cerebrospinal fluid findings, specific neuroimaging findings, and exclusion of alternative etiologies. Current treatment encompasses the identification and management of the inciting event, symptomatic treatment, and anticoagulation or immunosuppression.

Discordance of the Framingham cardiovascular risk score and the 2013 American College of Cardiology/American Heart Association risk score in systemic lupus erythematosus and rheumatoid arthritis

Despite the increasing use of the 2013 American College of Cardiology/American Heart Association (ACC/AHA) cardiovascular (CV) risk score in clinical practice, few studies have compared this score to the Framingham risk score among rheumatologic patients. We calculated Framingham and 2013 ACC/AHA risk scores in subjects with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) and assessed demographic, CV, and rheumatologic characteristics associated with discordant scores (high-risk ACC/AHA scores but low-risk Framingham scores). SLE and RA subjects drawn from two population-based cohort studies were assessed during in-person study visits. We used chi-squared tests and t tests to examine the association of discordant CV risk scores with baseline characteristics. Eleven (7.0%) of 157 SLE subjects and 11 (11.5%) of 96 RA subjects had discordant CV risk scores with high ACC/AHA scores and low Framingham scores. These findings did not significantly change when a 1.5 multiplier was applied to the Framingham score. Rheumatologic disease duration, high-sensitivity CRP levels, African-American race, diabetes, current use of anti-hypertensive medication, higher age, and higher systolic blood pressure were each significantly associated with discordant risk scores. Approximately 10% of SLE and RA subjects had discordant 10-year CV risk scores. Our findings suggest that the use of the 2013 ACC/AHA risk score could result in changes to lipid-lowering therapy recommendations in a significant number of rheumatologic patients. Prospective studies are needed to compare which score better predicts CV events in rheumatologic patients, especially those with risk factors associated with discordant risk scores.

Clinical Images: Ochronotic arthropathy

ogren’s syndrome–associated lymphoproliferation. Arthritis Rheum 2013;65:1085–96. 9. Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, et al, and the European Study Group on Classification Criteria for Sj€ ogren’s Syndrome. Classification criteria for Sj€ ogren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 2002;61:554–8. 10. Meffre E. The establishment of early B cell tolerance in humans: lessons from primary immunodeficiency diseases. Ann N Y Acad Sci 2011;1246:1–10. 11. Yurasov S, Wardemann H, Hammersen J, Tsuiji M, Meffre E, Pascual V, et al. Defective B cell tolerance checkpoints in systemic lupus erythematosus. J Exp Med 2005;201:703–11. 12. Kinnunen T, Chamberlain N, Morbach H, Cantaert T, Lynch M, Preston-Hurlburt P, et al. Specific peripheral B cell tolerance defects in patients with multiple sclerosis. J Clin Invest 2013;123:2737–41. 13. Shlomchik MJ, Craft JE, Mamula MJ. From T to B and back again: positive feedback in systemic autoimmune disease. Nat Rev Immunol 2001;1:147–53. 14. Kinnunen T, Chamberlain N, Morbach H, Choi J, Kim S, Craft J, et al. Accumulation of peripheral autoreactive B cells in the absence of functional human regulatory T cells. Blood 2013;121: 1595–603. 15. Ittah M, Gottenberg JE, Proust A, Hachulla E, Puechal X, Loiseau P, et al. No evidence for association between 1858 C/T single-nucleotide polymorphism of PTPN22 gene and primary Sj€ ogren’s syndrome. Genes Immun 2005;6:457–8.

Antimalarial myopathy in a systemic lupus erythematosus patient with quadriparesis and seizures: a case-based review

Weakness, seizures, and encephalopathy have a broad differential diagnosis in patients with systemic lupus erythematosus (SLE). We present a case of a 26-year-old female with a recent diagnosis of SLE who experienced a clinical deterioration with quadriparesis, seizures, and encephalopathy. Her quadriparesis was found to be secondary to biopsy-proven hydroxychloroquine-induced myopathy with concomitant inflammatory myopathy. Her seizures and encephalopathy were suspected to be multifactorial in the setting of sepsis and critical illness with possible contributions from neuropsychiatric manifestations of SLE and macrophage activation syndrome. She experienced a dramatic clinical recovery with discontinuation of hydroxychloroquine, treatment of lupus disease activity with mycophenolate mofetil and prednisone, and antibiotic treatment for methicillin-sensitive Staphylococcus aureus (MSSA) bacteremia. This case-based review provides a systematic approach to quadriparesis, seizures, and encephalopathy in patients with SLE and an evidence-based discussion of antimalarial myopathy, which is of critical importance given the widespread use of antimalarial medications for rheumatologic diseases.

Obesity Independently Associates with Worse Patient-Reported Outcomes in Women with Systemic Lupus Erythematosus

To determine whether obesity in women with systemic lupus erythematosus (SLE) is independently associated with worse patient‐reported outcomes (PROs).

A loss of sensation

The patient was in her usual state of good health until one week prior to presentation when she developed low back pain and numbness and tingling around her abdomen and lower back. Over the next several hours the numbness spread distally to involve her legs and feet, and it became difficult to walk. The following day she developed constipation and urinary retention. This article is protected by copyright. All rights reserved.