Cardiorespiratory fitness and cardiovascular risk in patients with ankylosing spondylitis: a cross-sectional comparative study.
ABSTRACT: To investigate the associations between cardiorespiratory fitness (CRF) and the level of cardiovascular (CV) risk factors in patients with ankylosing spondylitis (AS) and controls.In a cross-sectional comparative study, CRF was measured with a maximal treadmill test for estimation of peak oxygen uptake. Metabolic syndrome (MS), body composition, traditional CV risk factors, and inflammatory markers were assessed. Multivariable linear regression models were used to study the associations between CRF and CV risk factors. All models were adjusted for age, sex, and smoking, and for inflammation when C-reactive protein (CRP) level or erythrocyte sedimentation rate (ESR) were not already included as dependent variables.A total of 126 patients (mean ± SD age 47.9 ± 10.8 years) and 111 controls (mean ± SD age 52.1 ± 11.1 years) were included. There were significant inverse associations between CRF and body mass index, waist circumference, triglycerides, CRP level, and ESR (P < 0.001-0.03) for patients and controls. Also, significant associations were found between CRF and high-density lipoprotein (HDL) cholesterol (? = 0.03, P < 0.001) and blood pressure (BP; ? = -0.9 for systolic and ? = -0.6 for diastolic; P < 0.01) in controls, but these associations were not found in patients (? = 0, P = 0.69 for HDL cholesterol; ? = -0.04, P = 0.87 for systolic pressure; and ? = -0.14, P = 0.34 for diastolic pressure) (additional adjustments for medication). Higher CRF was associated with a lower risk for MS in both patients (odds ratio [OR] 0.91, P = 0.03) and controls (OR 0.89, P = 0.01).CRF was associated with favorable levels of CV risk factors and lower risk of MS in both AS patients and controls. However, established findings of an association between CRF and BP and HDL cholesterol in healthy adults were not confirmed in AS patients.
Project description:Lower levels of low-density lipoprotein (LDL) cholesterol may be associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). This study was undertaken to determine whether the complex relationship between levels of LDL and high-density lipoprotein (HDL) cholesterol and CV risk is different in RA patients as compared to non-RA controls.Using data from a US health insurance plan (2003-2012), we conducted a cohort study that included patients with RA and non-RA control subjects matched with regard to age, sex, and index date. The nonlinearity of associations between lipid levels and incidence of major adverse CV events (MACE) was tested. We used multivariable Cox proportional hazards regression models to examine for an interaction between lipid levels and RA status in relation to the risk of MACE, after adjustment for CV risk factors.In total, 16,085 RA patients and 48,499 non-RA controls were studied. The mean age was 52.6 years and 78.6% were women. The relationship between LDL cholesterol levels and incidence of MACE was nonlinear and similar between RA patients and non-RA controls (P for interaction?=?0.72). No significant increase in CV risk was observed between the lowest quintile of LDL cholesterol levels (?91.0 mg/dl) and the second, third, or fourth quintiles, whereas the highest quintile (>190.0 mg/dl) conveyed a 40% increase in risk of MACE (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.17-1.68). The relationship between HDL cholesterol levels and incidence of MACE was also nonlinear and similar between RA patients and non-RA controls (P for interaction?=?0.39). Compared to the lowest quintile of HDL cholesterol levels, each successive quintile was associated with a reduced risk of MACE (HR 0.45, 95% CI 0.48-0.72 for lowest quintile [?43.0 mg/dl] versus highest quintile [>71.0 mg/dl]).The complex relationship between LDL cholesterol levels, HDL cholesterol levels, and risk of MACE was nonlinear in RA patients and also not statistically significantly different from that in an age- and sex-matched non-RA cohort.
Project description:This study evaluated the prevalence and progression of subclinical carotid artery atherosclerosis in active rheumatoid arthritis (RA).Carotid arteries of RA patients were scanned using 3D ultrasound at baseline and 24 weeks for total plaque area, vessel wall volume, and intima-media thickness (IMT), as well as arterial stiffness measured using pulse wave velocity. Variables related to inflammation, lipids and cardiovascular (CV) risk were assessed for associations with plaque progression. Of 195 screened patients, 31 met inclusion criteria (66 Swollen joint count (SJC) plus 68 Tender joint count (TJC)?8 OR SJC plus TJC?4 with elevated acute phase reactants) and were enrolled (27 female; mean age 59.3±9.8years). Patients using lipid lowering drugs and uncontrolled comorbidities were excluded.Atherosclerotic plaque occurred in 35% and arterial wall hypertrophy (IMT?0.6mm) in 86% of patients. Most (68%) had an abnormal lipid profile characterized by reduced HDL and/or increased total cholesterol/HDL index, which was adversely affected by disease activity. Stepwise binary logistic regression analysis showed that Framingham risk score (OR=1.155, 95%CI:1.002-1.332, p=0.046) and ESR (OR=1.148, 95%CI:1.015-1.299, p=0.028) predicted plaque burden most strongly. Plaque progression was significantly associated with baseline higher hsCRP, ESR, and heavy smoking, but only hsCRP predicted plaque growth in multivariate regression analysis (p=0.004); and hsCRP was related to higher disease activity (r=0.443, p=0.016), LDL (r=0.544, p=0.007), and smoking (r=0.384, p=0.04).RA-related inflammation contributed to augmented CV burden in RA and might mediate its effect on atherosclerosis through hsCRP and modulation of the traditional CV risk factors, such as dyslipidemia.
Project description:Cardiovascular (CV) events are increased 36-fold in patients with end-stage renal disease. However, randomized controlled trials to lower LDL cholesterol (LDL-C) and serum total cholesterol (TC) have not shown significant mortality improvements. An inverse association of TC and LDL-C with all-cause and CV mortality has been observed in patients on chronic dialysis. Lipoproteins also may protect against infectious diseases. We used data from 37,250 patients in the international Monitoring Dialysis Outcomes (MONDO) database to evaluate the association between lipids and infection-related or CV mortality. The study began on the first day of lipid measurement and continued for up to 4 years. We applied Cox proportional models with time-varying covariates to study associations of LDL-C, HDL cholesterol (HDL-C), and triglycerides (TGs) with all-cause, CV, infectious, and other causes of death. Overall, 6,147 patients died (19.2% from CV, 13.2% from infection, and 67.6% from other causes). After multivariable adjustment, higher LDL-C, HDL-C, and TGs were independently associated with lower all-cause death risk. Neither LDL-C nor TGs were associated with CV death, and HDL-C was associated with lower CV risk. Higher LDL-C and HDL-C were associated with a lower risk of death from infection or other non-CV causes. LDL-C was associated with reduced all-cause and infectious, but not CV mortality, which resulted in the inverse association with all-cause mortality.
Project description:To evaluate long-term changes in cholesterol levels in patients with early rheumatoid arthritis (RA) who were randomized to begin treatment with methotrexate (MTX) monotherapy, MTX plus etanercept, or triple therapy (MTX plus sulfasalazine plus hydroxychloroquine) in the Treatment of Early Aggressive Rheumatoid Arthritis (TEAR) trial.Levels of total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol were analyzed in 416 patients participating in the TEAR trial, during 102 weeks of followup. Associations of cholesterol changes with disease activity and drug treatment were evaluated using repeated-measures analysis with mixed-effect linear models to model within-subject covariance over time.Mixed-effect models controlling for traditional cardiovascular (CV) risk factors, TEAR treatment, and baseline prednisone and statin use demonstrated significant inverse associations of RA disease activity with changes in cholesterol over time. Decreases in the 28-joint Disease Activity Score, the C-reactive protein level, or the erythrocyte sedimentation rate were associated with increases in levels of HDL cholesterol, LDL cholesterol, and total cholesterol in all treatment groups (P < 0.001-0.035). Triple therapy was strongly associated with higher levels of HDL cholesterol, lower levels of LDL cholesterol, and higher ratios of total cholesterol:HDL cholesterol (P < 0.001 for all) compared to MTX monotherapy or MTX plus etanercept therapy over the 2-year followup.Decreases in RA disease activity over long-term followup were associated with increases in cholesterol levels in patients with early RA treated with either biologic or nonbiologic therapies. The use of triple therapy during 2 years of followup was associated with higher HDL cholesterol levels, lower LDL cholesterol levels, and lower total cholesterol:HDL cholesterol ratios compared to those observed in patients who received MTX monotherapy or MTX plus etanercept combination therapy. Additional studies are needed to assess the effects of these cholesterol changes on CV events in patients with RA.
Project description:<b>Background:</b> Findings for associations between cardiorespiratory fitness (CRF) and cardiometabolic risk (CMR) factors are inconsistent, and the interactive association between CRF and fatness with CMR factors is unclear in children. Our study aimed to examine whether CRF and fatness are independently and interactively associated with CMR factors. <b>Methods:</b> We included 5,869 children aged 6-13 years in the analysis. Physical examinations, blood tests, and CRF were measured at baseline and 1 year later. Cardiometabolic risk score (CMRS) was computed by summing <i>Z</i> scores of waist circumference (WC), averaged systolic and diastolic blood pressure, glucose, high-density lipoprotein cholesterol (HDL-C, multiplied by -1), and triglycerides. <b>Results:</b> There was a high correlation between fatness and CRF in both boys and girls. High baseline CRF was independently associated with favorable changes in CMRS, BMI, WC, percent body fat (PBF), total cholesterol, LDL-C, and HDL-C (all <i>P</i> < 0.025). Improved CRF was independently associated with favorable changes in CMRS, BMI, WC, PBF, total cholesterol, LDL-C, HDL-C, triglycerides, and fasting glucose (all <i>P</i> < 0.0321). Baseline BMI was positively associated with changes in CMRS, WC, blood pressure, triglycerides, insulin, and HOMA-IR (all <i>P</i> < 0.0462). Low PBF at baseline was associated with favorable changes in CMRS, BMI, WC, blood pressure, HDL-C, triglycerides, insulin, and HOMA-IR (all <i>P</i> < 0.0423). The percentage of the total effect of baseline CRF on changes in CMRS, triglycerides, HDL-C, PBF, and WC mediated by baseline BMI was 66.0, 61.6, 40.3, 20.7, and 9.2%, respectively. Baseline CRF was a significant mediator for the association between baseline BMI and changes in CMRS (mediated by 4.3%), triglycerides (5.1%), and HDL-C (12.0%). An inverse association was found between baseline CRF and CMRS in children with high baseline BMI/PBF only. Improved CRF was associated with decreased BMI and WC in children with low baseline CRF. <b>Conclusions:</b> Fatness and CRF are each independently associated with changes in CMR factors. Fatness is a major mediator for the association between CRF and CMR factors, whereas the association between fatness and CMR factors is also mediated by CRF. The beneficial effect of high CRF on CMR factors was more evident in obese or unfit children.
Project description:OBJECTIVE: Low-grade chronic inflammation has been hypothesized to underlie the constellation of cardiometabolic risk factors, possibly by inducing insulin resistance. In the present study, we investigated associations between inflammation markers, insulin sensitivity (expressed as the ratio of the M value to the mean plasma insulin concentrations measured during the final 40 min of the clamp [M/I]), and a range of cardiometabolic risk factors in a large, healthy population. RESEARCH DESIGN AND METHODS: The Relationship between Insulin Sensitivity and Cardiovascular Disease (RISC) cohort includes 1,326 nondiabetic European men and women, aged between 30 and 60 years. We measured cardiometabolic risk factors and performed a hyperinsulinemic-euglycemic clamp. We determined total white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) as markers of chronic inflammation. RESULTS: WBC and ESR were both strongly associated with M/I. WBC and ESR were further associated with a range of cardiometabolic risk factors. Associations between WBC and HDL cholesterol, triglycerides, heart rate, fasting C-peptide, and insulin and 2-h insulin in men and women and between WBC and 2-h glucose in women remained significant after adjustment for both M/I and waist circumference. Associations between ESR and HDL cholesterol, heart rate, fasting, and 2-h insulin in men and women and between ESR and fat mass in women remained significant after adjustment for M/I and waist circumference. CONCLUSIONS: This study showed that low-grade chronic inflammation is associated with the cardiometabolic risk profile of a healthy population. Insulin resistance, although strongly associated with inflammation, does not seem to play a large intermediary role.
Project description:The relation between testosterone (T) plasma concentration and cardiovascular (CV) risk is unclear, with evidence supporting increased risk in men with low and high T levels. Few studies have assessed CV risk as a function of plasma T levels using objective biomarkers.To determine the relation between T levels and high-sensitivity CV risk biomarkers.Ten thousand forty-one male patients were identified in the database of a commercial clinical laboratory performing biomarker testing. Patients were grouped by total T concentration and associations with the following biomarkers were determined: cardiac troponin I (cTnI), endothelin-1 (ET-1), interleukin-6 (IL-6), tumor necrosis factor-? (TNF-?), interleukin-17A, N-terminal pro-B-type natriuretic peptide (NTproBNP), high-density lipoprotein (HDL) cholesterol, high-sensitivity C-reactive protein (hs-CRP), hemoglobin A1c (HbA1c), and leptin.Association of CV risk markers with levels of T in men.The median age of the cohort was 58 years (interquartile range = 48-68), and the median plasma T level was 420 ng/dL (interquartile range = 304-565); T levels did not vary with patient age. An inverse relation between plasma T levels and CV risk was observed for 9 of 10 CV markers: cTnI, ET-1, IL-6, TNF-?, NTproBNP, HDL cholesterol, hs-CRP, HbA1c, and leptin. Even after adjusting for age, body mass index, HbA1c, hs-CRP, and HDL cholesterol levels, the CV markers IL-6, ET-1, NTproBNP, and leptin were significantly associated with a T level lower than 250 ng/dL.Men with low T levels could be at increased risk for increased CV disease as seen by increased CV risk markers.This study was performed in a group of 10,041 men and is the first study to examine CV risk associated with circulating T levels using a large panel of 10 objective biomarkers. This study is limited by an absence of clinical data indicating whether men had pre-existing CV disease or other CV risk factors.Men with low plasma T levels exhibit increases in CV risk markers, consistent with a potential increased risk of CV disease. Pastuszak AW, Kohn TP, Estis J, Lipshultz LI. Low Plasma Testosterone Is Associated With Elevated Cardiovascular Disease Biomarkers. J Sex Med 2017;14:1095-1103.
Project description:OBJECTIVE:Patients with rheumatoid arthritis (RA) have an increased risk of coronary heart disease (CHD). Some RA therapies may modify this risk, but the underlying mechanisms are unclear. The cholesterol efflux capacity of high-density lipoprotein (HDL) is associated with a reduced CHD risk in non-RA populations; however, inflammation may impair the function of HDL. The aim of this study was to evaluate whether reduced inflammation resulting from treatment with methotrexate (MTX), adalimumab (ADA), or tocilizumab (TCZ) would increase the net cholesterol efflux capacity of HDL in patients with RA. METHODS:A longitudinal multicenter study repository (Treatment Efficacy and Toxicity in Rheumatoid Arthritis Database and Repository) provided clinical information for and serum samples from 70 patients with RA before and 6 months after starting treatment with a new drug (MTX [n?=?23], ADA [n?=?22], or TCZ [n?=?25]). Disease activity was measured using the Disease Activity Score in 28 joints using the erythrocyte sedimentation rate (DAS28-ESR). The net cholesterol efflux capacity was measured in paired serum samples using THP-1 macrophages, and total cellular cholesterol was measured by fluorometric assay. RESULTS:The DAS28-ESR decreased with all treatments (P?<?0.001). Net cholesterol efflux capacity was not significantly changed after 6 months of new RA therapy (mean?±?SD 36.9?±?17.3% units at baseline versus 38.0%?±?16.9% units at 6 months [P?=?0.58]). However, change in net cholesterol efflux capacity was associated with change in the DAS28-ESR (??=?-0.25, P?=?0.04). In a post hoc analysis of patients with impaired net cholesterol efflux capacity at baseline, treatment with TCZ resulted in significant improvement in net cholesterol efflux capacity (21.9?±?14.7% units at baseline versus 31.3%?±?12.8% units at 6 months [P?<?0.02]), but this was not observed with MTX or ADA. CONCLUSION:Net cholesterol efflux capacity of HDL cholesterol did not change significantly after 6 months of new RA therapy, except in patients with impaired baseline cholesterol efflux capacity who were receiving TCZ. Change in disease activity was associated with change in the net cholesterol efflux capacity.
Project description:We aimed to study the independent associations of sedentary time (ST), moderate-to-vigorous physical activity (MVPA), and objectively measured cardiorespiratory fitness (CRF) with clustered cardio-metabolic risk and its individual components (waist circumference, fasting glucose, HDL-cholesterol, triglycerides and blood pressure). We also investigated whether any associations between MVPA or ST and clustered cardio-metabolic risk were mediated by CRF. MVPA, ST, CRF and individual cardio-metabolic components were measured in a population-based sample of 341 adults (age 53.8 ± 8.9 years; 61% men) between 2012 and 2014. MVPA and ST were measured with the SenseWear pro 3 Armband and CRF was measured with a maximal exercise test. Multiple linear regression models and the product of coefficients method were used to examine independent associations and mediation effects, respectively. Results showed that low MVPA and low CRF were associated with a higher clustered cardio-metabolic risk (? = -0.26 and ? = -0.43, both p<0.001, respectively). CRF explained 73% of the variance in the association between MVPA and clustered cardio-metabolic risk and attenuated this association to non-significance. After mutual adjustment for MVPA and ST, CRF was the most important risk factor for a higher clustered cardio-metabolic risk (? = -0.39, p<0.001). In conclusion, because of the mediating role of CRF, lifestyle-interventions need to be feasible yet challenging enough to lead to increases in CRF to improve someone's cardio-metabolic health.
Project description:Aside from a decrease in the high-density lipoprotein (HDL) cholesterol levels, qualitative abnormalities of HDL can contribute to an increase in cardiovascular (CV) risk in end-stage renal disease (ESRD) patients undergoing chronic hemodialysis (HD). Dysfunctional HDL leads to an alteration of reverse cholesterol transport and the antioxidant and anti-inflammatory properties of HDL. In this study, a quantitative proteomics approach, based on iTRAQ labeling and nanoflow liquid chromatography mass spectrometry analysis, was used to generate detailed data on HDL-associated proteins. The HDL composition was compared between seven chronic HD patients and a pool of seven healthy controls. To confirm the proteomics results, specific biochemical assays were then performed in triplicate in the 14 samples as well as 46 sex-matched independent chronic HD patients and healthy volunteers. Of the 122 proteins identified in the HDL fraction, 40 were differentially expressed between the healthy volunteers and the HD patients. These proteins are involved in many HDL functions, including lipid metabolism, the acute inflammatory response, complement activation, the regulation of lipoprotein oxidation, and metal cation homeostasis. Among the identified proteins, apolipoprotein C-II and apolipoprotein C-III were significantly increased in the HDL fraction of HD patients whereas serotransferrin was decreased. In this study, we identified new markers of potential relevance to the pathways linked to HDL dysfunction in HD. Proteomic analysis of the HDL fraction provides an efficient method to identify new and uncharacterized candidate biomarkers of CV risk in HD patients.