The comparison of cardiovascular disease risk prediction scores and evaluation of subclinical atherosclerosis in rheumatoid arthritis: a cross-sectional study.

OBJECTIVES: Primary objectives estimated prevalence of traditional cardiovascular disease (CVD) risk factors and compared different CVD risk prediction algorithms in an Indian rheumatoid arthritis (RA) population. Secondary objectives evaluated associations between carotid intima-media thickness (CIMT) and subclinical atherosclerosis (SCA) with CVD risk factors and CVD risk scores. METHODS: The presence of CVD risk factors were recorded, and 10-year CVD risk was predicted using Framingham risk scoring (FRS) using lipids (FRS-Lipids), FRS using body mass index (FRS-BMI), QRISK-2, SCORE, and the algorithm recommended by ACC/AHA (ASCVD). CIMT was measured on the far-wall of the common carotid artery. Subclinical atherosclerosis was defined as CIMT > 0.9 mm or the presence of carotid plaque. RESULTS: A total of 332 patents were enrolled, 12% had diabetes mellitus, 21.4% hypertension, and 6.9% were current/past smokers. Proportions of RA with predicted 10-year CVD risk > 10% varied from 16.2 to 41.9% between scores. Highest magnitude of risk was predicted by FRS-BMI. Agreement between scores in predicting risk was moderate in general. Mean CIMT was 0.70 ± 0.15 mm. Age, male sex, and extra-articular manifestations associated with greater CIMT. All risk scores except SCORE moderately correlated with CIMT. About one-seventh had SCA defined as CIMT > 0.9 mm or the presence of carotid plaques, associated with increasing age, male gender, or higher ratio of total cholesterol to high-density lipoprotein cholesterol. ASCVD and QRISK-2 scores had maximum area under curve for distinguishing SCA. CONCLUSION: Individual CVD risk scores predict 10-year CVD risk differently in Indian patients with RA, and require validation for predicting hard end points (CVD events, mortality). Key Points • Diabetes mellitus and hypertension are the most prevalent cardiovascular disease risk factors in Indian patients with RA. • Individual cardiovascular risk prediction scores predict risk differently in Indian patients with RA, highest risk being predicted by the FRS-BMI. • Carotid intima-media thickness in RA associated with increasing age, male sex and extra-articular manifestations. • 14% RA had subclinical atherosclerosis, associated with increasing age, male sex, and higher total cholesterol to HDL-C ratio, best distinguished by ASCVD and QRISK-2 scores.

The association of polymorphic variants, rs2267788, rs1333049 and rs2383207 with coronary artery disease, its severity and presentation in North Indian population.

BACKGROUND: The polymorphic alleles of APOA5 (rs2266788 (C), rs3135506 (G)), LPA (rs10455872 (A), rs3798220 (G)) and 9p21.3 (rs1333049 (C), rs2383207(A)) have been reported in association with susceptibility of coronary artery disease (CAD) from genome wide association studies. We aimed to assess the association of genetic variants with coronary angiogram proven CAD, severity scored with modified Gensini score and association of risk for myocardial infraction (MI) in North Indian population. METHODS: We recruited 512 angiographic proven CAD patients (mean age 58.1±10.2years) and 272 controls (mean age 50.3±11.1years) with normal coronaries from North Indian population. The genotyping technique polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was employed for rs2266788, rs3135506 and rs10455872. Amplified refractory mutation system-PCR (ARMS-PCR) was used for genotyping of rs1333049, rs2383207 and rs3798220 genetic variants. RESULTS: The polymorphic risk allele of variants rs2266788 (C), rs1333049 (C), rs2383207 (A) and heterozygous polymorphic alleles of rs2266788 (TC) were significantly associated with CAD. The homozygous alleles of rs22667788 (CC) and rs1333049 (CC) had also been significantly associated with CAD. The significance of association of rs2266788 (C, CC, TC) and rs1333049 (C, CC) increases with severity of CAD. The presence of mutant allele of rs2266788 (C) was associated with risk of MI and unstable angina (UA). Also, homozygous risk allele of rs2266788 (CC) significantly associated with risk of MI and UA in patients of chronic stable angina (CSA) patients. Whereas, the risk allele of rs1333049 (C) have shown the association with MI and UA compared to controls. The genetic variants of rs3135506 (G), rs10455872 (A) and rs3798220 (G) have low frequency in our population and reflected no association with CAD. CONCLUSION: The polymorphic variants of Apo-A5; rs2266788 (C), 9p21.3; rs1333049 (C) rs2383207 (A) are associated with CAD, its severity and exerts the risk of MI in North Indian population.

Persistent expression and function of P-glycoprotein on peripheral blood lymphocytes identifies corticosteroid resistance in patients with systemic lupus erythematosus.

Corticosteroids (CS) are the mainstay of treatment in systemic lupus erythematosus (SLE) patients. However, some patients have poor response to CS treatment. Among the multiple mechanisms of CS resistance, overexpression of P-glycoprotein (P-gp) on peripheral blood lymphocytes (PBL) may be one of them as this result in efflux of CS from lymphocytes. Thus, we evaluated the role of P-gp protein on PBLs in patients with SLE in its response to CS therapy. SLE patients (n = 42) (fulfilling ACR revised criteria) who were naïve to CS and immunosuppressive drugs were enrolled. Disease activity was assessed using SLE disease activity index (SLEDAI) and expression, and function of P-gp was evaluated by flow cytometry at baseline and after 3 months of therapy with CS. At 3 months, patients with SLEDAI >4 and SLEDAI ≤4 were grouped as nonresponders and responders, respectively. P-gp expression was significantly increased on PBLs of SLE patients as compared to healthy controls (p < 0.001). P-gp expression and function correlated with SLEDAI (r = 0.49, p = 0.005; and r = 0.49, p = 0.001, respectively). P-gp expression and function were not different in responders and nonresponders at baseline. However, at 3 months of CS therapy, P-gp expression and function decreased in responders (p < 0.001 and p < 0.005, respectively), whereas in nonresponders, it remained unchanged. Persistent overexpression and activity of P-gp are associated with poor response to CS in CS naïve patients of SLE.

Multidrug resistance protein-1 expression, function and polymorphisms in patients with rheumatoid arthritis not responding to methotrexate.

OBJECTIVE: To study the expression, function and polymorphism of MDR-1 protein on the peripheral blood lymphocytes in patients with RA following treatment with MTX and its relationship with response to therapy. METHODS: RA patients naïve to MTX/DMARD- and glucocorticoid were enrolled. Expression and function of MDR-1 was carried out by flow cytometry at baseline and after 4 months of therapy. MDR-1 expression was measured by relative fluorescence intensities and percentage of positive cells. MDR-1 function was assessed by Rhodamine efflux in presence or absence of verapamil. Patients with reduction in disease activity score 28 ≥1.2 were defined as responders and <1.2 as non-responders. Three single nucleotide polymorphisms in MDR-1 gene, 3435T, 1236T and 2677T/A were studied. RESULTS: Fifty-two patients of RA were grouped into responders (n = 41), and non-responders (n = 11) as per the defined criteria. There was no difference between the groups in terms of age, sex ratio or duration of illness, MTX dose and follow-up duration. The expression and function of the MDR-1 protein reduced significantly in the responder group after the treatment with MTX when compared to the baseline evaluation. The decrease was significant when compared to the non-responders at the fourth month. MDR-1 expression and function either increased or remained the same in the non-responder group after treatment with MTX. MTX unresponsiveness was not related to any of the three polymorphisms studied. CONCLUSION: Persistent expression and function of MDR-1 identifies a subset of RA patients not responding to MTX. Its early recognition may help in appropriately modulating therapy.

Magnetic-nanoparticle-doped carbogenic nanocomposite: an effective magnetic resonance/fluorescence multimodal imaging probe.

A novel and facile approach is developed to synthesize a magnetic nanoparticle (iron oxide)-doped carbogenic nanocomposite (IO-CNC) for magnetic resonance (MR)/fluorescence imaging applications. IO-CNC is synthesized by thermal decomposition of organic precursors in the presence of Fe(3) O(4) nanoparticles with an average size of 6 nm. IO-CNC shows wavelength-tunable fluorescence properties with high quantum yield. Magnetic studies confirm the superparamagnetic nature of IO-CNC at room temperature. IO-CNC shows MR contrast behavior by affecting the proton relaxation phenomena. The measured longitudinal (r(1) ) and transverse (r(2) ) relaxivity values are 4.52 and 34.75 mM(-1) s(-1) , respectively. No apparent cytotoxicity is observed and the nanocomposite shows a biocompatible nature. In vivo MR studies show both T(1) and T(2) * contrast behavior of the nanocomposite. Fluorescence imaging indicates selective uptake of IO-CNC by macrophages in spleen.