Vitamin D deficiency is highly prevalent in Indian children of northern, western and southern states. Serum 25 hydroxy cholecalferol (ng/ml) was analyzed in 310 children and adolescents of pediatric hospital of Kolkata, India. Serum calcium (mg/dl), phosphorous (mg/dl) and alkaline phosphatase (IU/L) data was obtained. Median 25(OH)D was 19 ng/ml. 19.2 % of population had serum 25(OH)D < 10 ng/ml (severe deficiency), 52.9 % had <20 ng/ml (deficiency), 24.5 % had 20-29 ng/ml (insufficiency) and 22.6 % had >30 ng/ml (optimum). Deficiency was highest in adolescents (86.1 %), followed by school children (61.0 %), lowest in pre-school children (41.6 %). 25(OH)D concentrations was lowest in winters (P = 0.002) and spring (P = 0.03) compared to summer. There was no correlation with calcium (P = 0.99), phosphorous (P = 0.23) and ALP (P = 0.63). There is high prevalence of vitamin D deficiency in children and adolescents of eastern India. Prevalence was lower in younger subjects. 25(OH)D did not correlate with bone mineral markers.
IMPORTANCE Psoriasis, a chronic inflammatory skin disease associated with accelerated noncalcified coronary burden (NCB) by coronary computed tomography angiography (CCTA), accelerates lipoprotein oxidation in the form of oxidized modified lipoproteins. A transmembrane scavenger receptor for these oxidized modified lipoproteins is lectinlike oxidized low-density lipoprotein receptor-1 (LOX-1), which has been reported to be associated with coronary artery disease. It is unknown whether this receptor is associated with coronary artery disease in psoriasis.OBJECTIVE To assess the association between soluble LOX-1 (sLOX-1) and NCB in psoriasis over time. DESIGN, SETTING, AND PARTICIPANTSIn a cohort study at the National Institutes of Health, 175 consecutive patients with psoriasis were referred from outpatient dermatology practices between January 1, 2013, and October 1, 2017. A total of 138 consecutively recruited patients with psoriasis were followed up at 1 year.EXPOSURES Circulating soluble lectinlike oxidized low-density lipoprotein receptor-1 levels were measured blindly by field scientists running undiluted serum using an enzyme-linked immunosorbent assay. MAIN OUTCOMES AND MEASURESCoronary computed tomography angiography scans were performed to quantify NCB in all 3 major epicardial coronary arteries by a reader blinded to patient demographics, visit, and treatment status. RESULTS Among the 175 patients with psoriasis, the mean (SD) age was 49.7 (12.6) years and 91 were men (55%). The cohort had relatively low median cardiovascular risk by Framingham risk score (median, 2.0 [interquartile range (IQR), 1.0-6.0]) and had a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) suggestive of overweight profiles (29.6 [6.0]). Elevated sLOX-1 levels were found in patients with psoriasis compared with age-and sex-matched controls (median, 210.3 [IQR,.0]; P < .001), and were associated with Psoriasis Area Severity Index (PASI) score (β = 0.23; 95% CI, 0.082-0.374; P = .003). Moreover, sLOX-1 was associated with NCB independent of hyperlipidemia status (β = 0.11; 95% CI, 0.016-0.200; P = .023), an association which persisted after adjusting for traditional cardiovascular risk factors, statin use, and biologic psoriasis treatment (β = 0.10; 95% CI, 0.014-0.193; P = .03). At 1 year, in those who had clinical improvement in PASI (eg, >50% improvement), a reduction in sLOX-1 (median, 311.1 [IQR, 224.2 [IQR,]; P = .01) was associated with a reduction in NCB (β = 0.14; 95% CI, 0.028-0.246; P = .02). CONCLUSIONS AND RELEVANCESoluble lectinlike oxidized low-density lipoprotein receptor-1 levels were elevated in patients with psoriasis and were associated with severity of skin disease. Moreover, sLOX-1 associated with NCB independent of hyperlipidemia status, suggesting that inflammatory sLOX-1 induction may modulate lipid-rich NCB in psoriasis. Improvement of skin disease was associated with a reduction of sLOX-1 at 1 year, demonstrating the potential role of sLOX-1 in inflammatory ...
Traditional cardiovascular disease (CVD) risk factors, such as hypertension, dyslipidemia and diabetes do not explain the increased CVD burden in systemic lupus erythematosus (SLE). The oxidized-LDL receptor, LOX-1, is an inflammation-induced receptor implicated in atherosclerotic plaque formation in acute coronary syndrome, and here we evaluated its role in SLE-associated CVD. SLE patients have increased sLOX-1 levels which were associated with elevated proinflammatory HDL, oxLDL and hsCRP. Interestingly, increased sLOX-1 levels were associated with patients with early disease onset, low disease activity, increased IL-8, and normal complement and hematological measures. LOX-1 was increased on patient-derived monocytes and low-density granulocytes, and activation with oxLDL and immune-complexes increased membrane LOX-1, TACE activity, sLOX-1 release, proinflammatory cytokine production by monocytes, and triggered the formation of neutrophil extracellular traps which can promote vascular injury. In conclusion, perturbations in the lipid content in SLE patients' blood activate LOX-1 and promote inflammatory responses. Increased sLOX-1 levels may be an indicator of high CVD risk, and blockade of LOX-1 may provide a therapeutic opportunity for ameliorating atherosclerosis in SLE patients.
Background Blockade of the lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1) is a potentially attractive mechanism for lowering inflammatory and lipid risk in patients with atherosclerosis. This study aims to assess the safety, tolerability, and target engagement of MEDI6570, a high‐affinity monoclonal blocking antibody to LOX‐1. Methods and Results This phase 1, first‐in‐human, placebo‐controlled study (NCT03654313) randomized 88 patients with type 2 diabetes to receive single ascending doses (10, 30, 90, 250, or 500 mg) or multiple ascending doses (90, 150, or 250 mg once monthly for 3 months) of MEDI6570 or placebo. Primary end point was safety; secondary and exploratory end points included pharmacokinetics, immunogenicity, free soluble LOX‐1 levels, and change in coronary plaque volume. Mean age was 57.6/58.1 years in the single ascending doses/multiple ascending doses groups, 31.3%/62.5% were female, and mean type 2 diabetes duration was 9.7/8.7 years. Incidence of adverse events was similar among cohorts. MEDI6570 exhibited nonlinear pharmacokinetics, with terminal half‐life increasing from 4.6 days (30 mg) to 11.2 days (500 mg), consistent with target‐mediated drug disposition. Dose‐dependent reductions in mean soluble LOX‐1 levels from baseline were observed (>66% at 4 weeks and 71.61–82.96% at 10 weeks in the single ascending doses and multiple ascending doses groups, respectively). After 3 doses, MEDI6570 was associated with nonsignificant regression of noncalcified plaque volume versus placebo (−13.45 mm 3 versus −8.25 mm 3 ). Conclusions MEDI6570 was well tolerated and demonstrated dose‐dependent soluble LOX‐1 suppression and a pharmacokinetic profile consistent with once‐monthly dosing. Registration URL: https://clinicaltrials.gov/ ; Unique identifier: NCT03654313.
Cardiac involvement is the most important prognostic factor in primary amyloidosis (AL). The clinical presentation of amyloid cardiomyopathy is varied and may manifest as heart failure, brady or tachyarrhythmias, syncope, angina and rarely with features of hypertrophic cardiomyopathy and advanced symptomatic conduction system disease. The management of amyloid cardiomyopathy has always been a dilemma, as most of the drugs used in congestive heart failure are contraindicated. This report describes a 70-year-old woman who presented with syncope, severe diastolic heart failure, features of hypertrophic cardiomyopathy and severe symptomatic conduction system disease requiring a pacemaker. Amyloidosis was diagnosed on endomyocardial biopsy after abdominal fat aspirate was negative for amyloid. The patient eventually expired due to end-stage congestive heart failure.
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