Total cholesterol and LDL levels decrease before rheumatoid arthritis

Department of Health Sciences Research, Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Annals of the rheumatic diseases (Impact Factor: 10.38). 10/2009; 69(7):1310-4. DOI: 10.1136/ard.2009.122374
Source: PubMed

ABSTRACT To compare lipid profiles in patients with rheumatoid arthritis (RA) and in non-RA subjects during the 5 years before and 5 years after the RA incidence/index date.
Lipid measures were abstracted in a population-based incident cohort of patients with RA (1987 American College of Rheumatology criteria) first diagnosed between 1 January 1988 and 1 January 2008 and in non-RA subjects. Random-effects models adjusting for age, sex and calendar year were used to examine trends in lipid profiles, accounting for multiple measurements for each subject.
The study population included a cohort of 577 patients with RA (a total of 3088 lipid measurements) and 540 non-RA subjects (a total of 3048 lipid measurements). There were significant decreases in total (TC) and low-density lipoprotein cholesterol (LDL) levels in the RA cohort during the 5 years before RA, compared with the non-RA cohort (p<0.001). Decreases of 0.58 mmol/l for TC and 0.61 mmol/l for LDL were noted in RA compared with decreases of 0.09 mmol/l for TC and 0.22 mmol/l for LDL in the non-RA cohort. Trends in other lipid measures (triglycerides (TGs) and high-density lipoprotein cholesterol (HDL)) were similar in RA and non-RA cohorts during the 5 years before and 5 years after the RA incidence/index date. During the 5 years before the RA incidence/index date, the proportion of patients with RA with elevated TC or LDL measures, but not with abnormal HDL and TG measures, significantly decreased compared with non-RA subjects. Lipid-lowering drugs (statins in particular) were less often prescribed to patients with RA than to non-RA subjects (34% vs 41%; p=0.02).
TC and LDL levels and the prevalence of abnormal TC or LDL measures decreased significantly during the 5 years before the RA incidence/index date in patients with RA as compared with the non-RA cohort. These trends in lipid profile in RA are unlikely to be solely due to lipid-lowering treatment.

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Available from: Hilal Maradit Kremers, Nov 26, 2014
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    • "Such an autoimmune “pattern” has been reported in the TARF study [12, 27]. Reduced levels of LDL-cholesterol have been reported to similarly precede the clinical onset of rheumatoid arthritis [28]. Epidemiological data showing paradoxical inverse association of lipid levels with cardiovascular disease risk in rheumatoid arthritis patients have been reviewed [29]. "
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    ABSTRACT: Background The definition of glomerular hyperfiltration has not been agreed upon and the pathophysiological mechanisms have not been well explored. Low serum creatinine concentrations may be associated with increased risk of coronary heart disease (CHD) or cardiopulmonary events the impact of which needs further study. Methods Consecutive applicants to a cardiovascular hospital free of moderate/severe chronic kidney disease (age 55.6 ± 8.2 years) were grouped into those without (“healthy”, n = 469) and with CHD (320 stable and acute coronary syndrome cases) at baseline and into sex-specific quartiles of CKD-EPI equation-estimated glomerular filtration rate (eGFR). New or recurrent cardiovascular (myocardial infarction, stroke, heart failure [HF]) events, obstructive pulmonary disease (COPD) and death were determined during 3-years’ follow-up. Results Among 25 deaths and 75 cardiopulmonary events, HF was the leading nonfatal event. Age, serum uric acid and left ventricular ejection fraction proved the best independent inverse covariates of eGFR in the “healthy” sample. The highest eGFR quartile (“hyperfiltrators”), exhibiting significantly lower serum LDL-cholesterol levels, significantly predicted the combined outcome (at a RR of 6) in “healthy” subjects, after adjustment for sex, age, body mass index, smoking status and presence of hypertension. This finding was paralleled by the highest eGFR quartile calculated also by the MDRD equation, replicating this also in the CHD group. Conclusion Renal “hyperfiltrators” represent individuals with autoimmune activation (involving serum creatinine, partly escaping assay), are misclassified into optimal renal function and actually are at significantly higher risk of death, HF or cardiopulmonary events. Low serum creatinine levels may represent a clue to the existence of autoimmune activation.
    BMC Nephrology 10/2014; 15(1):160. DOI:10.1186/1471-2369-15-160 · 1.69 Impact Factor
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    • ". 9. A precipitous decline in serum levels of total and LDL cholesterol was reported to precede the incidence of clinical rheumatoid arthritis [4]. Excess cardiovascular risk in rheumatoid arthritis also seems to be preceded by a lowering of total cholesterol and is followed by immune processes typically illustrated by positivity of rheumatoid factor [5]. 10. "
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    ABSTRACT: Insight is provided herein into the novel mechanisms of cardiometabolic risk. Previous reports, including the epidemiological work of the Turkish Adult Risk Factor study, indicated that proinflammatory state and oxidative stress are crucial for evaluating cardiometabolic risk. Autoimmune pathways in the course of oxidative stress are major determinants of cardiorenal and metabolic risk. The latter encompasses metabolic syndrome, type 2 diabetes, coronary heart disease, and chronic kidney disease (CKD). Along with platelet-activating factor, acetylhydrolase, creatinine, thyroid stimulating hormone, acylation-stimulating protein, asymmetric dimethylarginine, and serum lipoprotein[Lp](a) are triggers of systemic low-grade inflammation and enhanced autoimmune reactions. Related studies are analyzed in the current review. Lp(a) plays a crucial role by taking part in the immune activation, thereby accelerating the course of diabetes, CKD, and other chronic disorders. Populations prone to impaired glucose tolerance, and particularly peri- and postmenopausal women, are at high risk of developing related vascular complications.
    Current pharmaceutical design 04/2013; 20(4). DOI:10.2174/138161282004140213145551 · 3.45 Impact Factor
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    • "Patients in the GO-BEFORE trial were MTX-naïve, and many responded well to MTX, which may explain why patients in this trial who received MTX monotherapy also had favourable changes in many of these markers. Others have shown that TC and LDL levels decrease during the 5 years prior to an RA diagnosis, suggesting a possible relationship to inflammation.28 This may partially account for the increase in lipid levels among patients responding to treatment (MTX alone, golimumab alone or combination therapy). "
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    ABSTRACT: Objectives To assess the effect of golimumab, with or without methotrexate (MTX), on serum lipids and inflammatory markers of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) in two phase 3, randomised, placebo-controlled trials (GO-BEFORE and GO-FORWARD). Methods Patients in GO-BEFORE (n=637, MTX-naïve) and GO-FORWARD (n=444, MTX-inadequate response) were randomised to placebo+MTX, golimumab 100 mg+placebo, golimumab 50 mg+MTX, or golimumab 100 mg+MTX. Subcutaneous injections (placebo and golimumab) were given every 4 weeks. Patients with an insufficient response entered early escape at week 16 (GO-FORWARD) or 28 (GO-BEFORE). All placebo+MTX patients in GO-FORWARD crossed over to golimumab 50 mg+MTX at week 24. Changes from baseline to weeks 14 (GO-FORWARD) or 24 (GO-BEFORE), and 52 in serum lipid levels and inflammatory markers were assessed. Results At week 14 in the GO-FORWARD trial, total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) increased in golimumab+MTX patients versus MTX-only patients (16.00 vs 2.00 (p<0.001); 3.00 vs 0.00 (p<0.05); 8.00 vs 4.00 (p<0.001); respectively); favourable changes in LDL subfractions were only observed in golimumab-treated patients. At week 24 in GO-BEFORE, TC and LDL increased, and LDL subfractions improved in the MTX-only and golimumab+MTX groups. Inflammatory markers of CVD risk improved significantly with golimumab+MTX versus placebo+MTX in both studies and were generally maintained through week 52. Atherogenic indices were generally stable. Conclusions While TC and LDL levels increased mildly in RA patients receiving golimumab+MTX, atherogenic indices generally remained stable, favourable changes in LDL subfractions were observed, and inflammatory markers improved.
    Annals of the rheumatic diseases 01/2013; 73(1). DOI:10.1136/annrheumdis-2012-202089 · 10.38 Impact Factor
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