Long-term effects of large-volume liposuction on metabolic risk factors for coronary heart disease

Abdominal obesity is associated with metabolic risk factors for coronary heart disease (CHD). Although we previously found that using liposuction surgery to remove abdominal subcutaneous adipose tissue (SAT) did not result in metabolic benefits, it is possible that postoperative inflammation masked the beneficial effects. Therefore, this study provides a long-term evaluation of a cohort of subjects from our original study. Body composition and metabolic risk factors for CHD, including oral glucose tolerance, insulin resistance, plasma lipid profile, and blood pressure were evaluated in seven obese (39 +/- 2 kg/m(2)) women before and at 10, 27, and 84-208 weeks after large-volume liposuction. Liposuction surgery removed 9.4 +/- 1.8 kg of body fat (16 +/- 2% of total fat mass; 6.1 +/- 1.4 kg decrease in body weight), primarily from abdominal SAT; body composition and weight remained the same from 10 through 84-208 weeks. Metabolic endpoints (oral glucose tolerance, homeostasis model assessment of insulin resistance, blood pressure and plasma triglyceride (TG), high-density lipoprotein (HDL)-cholesterol, and low-density lipoprotein (LDL)-cholesterol concentrations) obtained at 10 through 208 weeks were not different from baseline and did not change over time. These data demonstrate that removal of a large amount of abdominal SAT by using liposuction does not improve CHD metabolic risk factors associated with abdominal obesity, despite a long-term reduction in body fat.     

Association of lecithin-cholesterol acyltransferase activity and low-density lipoprotein heterogeneity with atherosclerotic cardiovascular disease risk: a longitudinal pilot study

Background

Lecithin-cholesterol acyltransferase (LCAT) is believed to be involved in reverse cholesterol transport, which is known to play a key role in suppression of atherosclerosis. However, recent investigations have demonstrated that higher LCAT activity, measured in terms of the serum cholesterol esterification rate by an endogenous substrate method, is associated with increased formation of triglyceride (TG)-rich lipoproteins (TRLs), leading to a decrease in the low-density lipoprotein (LDL) particle size. The purpose of this hospital-based longitudinal study was to clarify the causal relationship between changes in the LCAT activity and changes in the LDL-particle size.

Methods

The subjects were a total of 335 patients, derived from our previous study cohort, with one or more risk factors for atherosclerotic cardiovascular disease (ASCVD). For this study, we measured the LDL-particle size (relative LDL migration [LDL-Rm value]) by polyacrylamide gel electrophoresis in the subjects, along with the changes in the LCAT activity, at the end of a follow-up period of at least 1 year.

Results

The results revealed that the absolute change (Δ) in the LDL-particle size increased significantly as the quartile of Δ LCAT activity increased (p =?0.01). A multi-logistic regression adjusted-analysis revealed that Δ LCAT activity in the fourth quartile as compared to that in the first quartile was independently predictive of an increased LDL-particle size (odds ratio [95% confidence interval]: 2.03 [1.02/4.04], p =?0.04). Moreover, the ? LCAT activity was also positively correlated with ? TRL-related markers (i.e., TG, remnant particle-like cholesterol [RLP-C], apolipoprotein B, apolipoprotein C-2, and apolipoprotein C-3).

Conclusions

The results lend support to the hypothesis that increased LCAT activity may be associated with increased formation of TRLs, leading to a reduction in the LDL-particle size in patients at a high risk for ASCVD. To reduce the risk of ASCVD, it may be important to focus not only on the quantitative changes in the serum LDL-cholesterol levels, but also on the LCAT activity.

Trial registration

UMIN (https://upload.umin.ac.jp/cgi-bin/ctr/ctr_reg_list.cgi) Study ID: UMIN000033228 retrospectively registered 2 July 2018.

     

The effects of surgically removing subcutaneous fat on the metabolic profile and insulin sensitivity in obese women after large-volume liposuction treatment.

The aim of this study was to identify the effects of surgically removing subcutaneous fat on the metabolic profile and insulin sensitivity in obese women after large-volume liposuction treatment. An open clinical trial with a non-intervention parallel group was carried out on 12 young, obese women. After randomization, six volunteers were selected to the surgical intervention consisting of large-volume liposuction; the other six women were considered as the non-intervention group. Metabolic profiles and insulin tolerance tests to assess insulin sensitivity were performed on all volunteers before intervention or non-intervention and 21 - 28 days afterwards. There were a significant decrease in glucose (4.9 +/- 0.4 vs. 4.6 +/- 0.2 mmol/l, p < 0.05) and uric acid (250.8 +/- 56.2 vs. 224.0 +/- 53.4 micromol/l, p < 0.05) levels after liposuction; insulin sensitivity improved after the surgical intervention (4.3 +/- 0.9 vs. 5.3 +/- 0.8 %/min, p = 0.046). In conclusion, surgical removal of subcutaneous fat by large-volume liposuction led to an improvement in insulin sensitivity and a decrease in glucose and uric acid concentrations.     

Metabolite signatures of diabetes with cardiovascular disease: a pilot investigation

Introduction

Type 2 diabetes (T2D) is an independent risk factor in the development of cardiovascular disease. However, there are significant limitations in the detection of the metabolic disturbances in hyperglycemia that lead to vascular dysfunction.

Objectives

The goals of the study were: (i) to identify circulating metabolites discriminating T2D and normoglycemia, and (ii) to assess phenotypic correlations of identified metabolites with other cardiometabolic risk traits (CMTs).

Methods

We have generated global and targeted metabolomic profiles using AB Sciex TripleTOF 5600 and Thermo Scientific Q Exactive Plus using serum samples of patients and healthy controls from a Punjabi population from India.

Results

In global profiling, we identified eight unknown molecules that currently do not match to any spectra in public databases. Additionally, serum levels of pyroglutamate, imidazole-4-acetate, tyramine-O-sulphate and 2,3-diphosphoglycerate were significantly elevated (2–5 fold) and betaine-aldehyde was reduced (fourfold) in patients. In targeted screening of amino acids and sugars, increased concentrations of serine, inositol, and threonine strongly correlated with T2D in both genders, while N-acetyl-l-alanine was reduced (58 fold) in men and glutamine was increased (fourfold) in women. Using random forest and ROC (AUC) analyses, we further cross-validated the predictive abilities of these molecules. Inositol, serine and threonine were among the top informative biomarkers in both genders while N-acetyl-l-alanine was highly confined to men.

Conclusions

Our study has identified several metabolites whose concentrations were altered in T2D. Although further study is needed in larger datasets, the identified metabolites (unknown or known) point towards shared etiological pathways underlie diabetes and vascular disease which can be targeted for potential therapeutics or biomarkers discovery.

     

Familial genetic risk factors in premature cardiovascular disease: a family study

Cardiovascular disease (CVD) is closely associated with familial predisposition. The aim of the present study was to investigate predisposing risk factors in the family of a young patient who underwent coronary artery bypass graft surgery due to CVD. The father and uncle of the patient died at an early age due to myocardial infarction. Various stages of CVD were identified in both of the patient’s brothers (28 and 32 years of age). Biochemical tests (fasting blood glucose, lipid profile, urea, creatinine and liver enzymes) and a complete blood count (haemoglobin, haematocrit, white blood cell count, and platelet count) were performed. Physiological coagulation inhibitory factors (protein C, protein S, and antithrombin III), prothrombotic genetic risk factors (factor V Leiden, plasminogen activator inhibitor-1, methylenetetrahydrofolate reductase A1C and C6T, angiotensin-converting enzyme, β-fibrinogen, glycoprotein IIIa and factor XIII) and homocysteine levels were evaluated in all cases. Defects were observed in many genetic factors and in the systems regulated by these factors. The results were compatible with those reported in the literature. In conclusion, it is possible to determine a specific family history in young adults with CVD. From this perspective, the emergence of more serious CVD may be prevented by providing disease-related information to the other family members and implementing preventive measures.     

The cardiovascular profile of soccer referees: an echocardiographic study

Background

Previous studies demonstrated a modest association between C-Reactive Protein (CRP), stenosis of carotid artery, and carotid Intima-Media Thickness (IMT) in general population. During present study, we aimed to evaluate the relationship between High Sensitivity C-Reactive Protein (hsCRP) and Common Carotid Intima-Media Thickness (CCIMT) in patients who candidate for Coronary Artery Bypass Grafting (CABG).

Methods

The study subjects were enrolled from patients with coronary arteries disease referred from Shahid Madani Hospital (Tabriz, Iran), who have been candidate for elective CABG from January 2005 to August 2007. The common carotid arteries were evaluated with high-resolution B-mode ultrasonography using a 7.5- MHz linear-array transducer to determine the IMT and grade of stenosis. Serum hsCRP level was measured using commercially available enzyme linked immunosorbent assay kit.

Results

Finally, information of 176 CABG candidates was analysed. The mean age of participants was 62.71 ± 9.45 years with 1.63 male to female ratio. The mean of CCIMT was 0.69 ± 0.54 mm. Although there was no significant correlation between serum hsCRP level and CCIMT in patients without carotid stenosis (p=0.113, r=0.186), participants with common carotid artery stenosis had higher levels of serum hsCRP than participants without stenosis (2.42+/-1.30 vs. 1.20+/-0.97 mg/dl; p=0.009).

Conclusion

Study results showed that there was no correlation between serum hsCRP level and CCIMT in patients without carotid stenosis, but patients with common carotid artery stenosis had higher levels of serum hsCRP than patients without stenosis.     

Lactation and cardiovascular risk factors in mothers in a population-based study: the HUNT-study

ABSTRACT: BACKGROUND: Lactation has beneficial short term effects on maternal metabolic health, but the long term effects are less well known. METHODS: We studied the association between lifetime duration of lactation and cardiovascular risk factors in mothers later in life among 21,368 parous women aged 20 to 85 years attending the second Nord-Trondelag Health Study (HUNT2) in 1995-1997, Norway, a cross-sectional population-based study. General linear modelling was used to calculate mean values of known cardiovascular risk factor levels in five categories of lifetime duration of lactation. Logistic regression was conducted to estimate odds ratios of hypertension, obesity and diabetes. RESULTS: Among women aged 50 years or younger, lifetime duration of lactation was significantly and inversely associated with body mass index (P-trend, < 0.001), waist circumference (P-trend, < 0.001), systolic and diastolic blood pressure (both P-trends, < 0.001), and serum levels of triglycerides, total cholesterol and low density lipoprotein cholesterol (all P-trends, < 0.001) after adjustment for covariates. Parous women aged 50 years or younger who had never lactated had higher prevalence of hypertension, obesity and diabetes. In this age group, compared to women who had lactated for 24 months or more, parous women who had never lactated had an OR for hypertension of 1.88 (95% CI 1.41, 2.51), an OR for obesity of 3.37 (95% CI 2.51, 4.51) and an OR for diabetes of 5.87 (95% CI 2.25, 15.3). Among women older than 50 years there were no clear associations. CONCLUSION: Lifetime duration of lactation was associated with long term reduced cardiovascular risk levels in mothers aged 50 years or younger.     

Adult patients with congenital adrenal hyperplasia have elevated blood pressure but otherwise a normal cardiovascular risk profile

Objective

Treatment with glucocorticoids and mineralocorticoids has changed congenital adrenal hyperplasia (CAH) from a fatal to a chronic lifelong disease. Long-term treatment, in particular the chronic (over-)treatment with glucocorticoids, may have an adverse effect on the cardiovascular risk profile in adult CAH patients. The objective of this study was to evaluate the cardiovascular risk profile of adult CAH patients.

Design

Case-control study.

Patients and Measurements

In this case-control study the cardiovascular risk profile of 27 adult CAH patients and 27 controls, matched for age, sex and body mass index was evaluated by measuring ambulatory 24-hour blood pressure, insulin sensitivity (HOMA-IR), lipid profiles, albuminuria and circulating cardiovascular risk markers (PAI-1, tPA, uPA, tPA/PAI-1 complex, hsCRP, adiponectin, IL-6, IL-18 and leptin).

Results

24-Hour systolic (126.3 mmHg±15.5 vs 124.8 mmHg±15.1 in controls, P = 0.019) and diastolic (76.4 mmHg±12.7 vs 73.5 mmHg±12.4 in controls, P<0.001) blood pressure was significantly elevated in CAH patients compared to the control population. CAH patients had higher HDL cholesterol levels (P<0.01), lower hsCRP levels (P = 0.03) and there was a trend toward elevated adiponectin levels compared to controls. Other cardiovascular risk factors were similar in both groups.

Conclusion

Adult CAH patients have higher ambulatory blood pressure compared to healthy matched controls. Other cardiovascular risk markers did not differ, while HDL-cholesterol, hsCRP and adiponectin levels tended to be more favorable.     

A pilot Croatian survey of risk factor (CRO-SURF) management in patients with cardiovascular disease

A pilot survey was performed to determine the presence of known risk factors for cardiovascular disease in Croatian patients with diagnosed coronary heart disease (CHD) using a new questionnaire. The idea was to test this new and very simple questionnaire but also to compare the data collected in this pilot survey with the results of the last Croatian national survey (TASPIC-CRO V) and so to obtain the information whether secondary prevention has improved between 2003 and 2010. 122 patients with established CHD (88 men, 34 women, mean age 66.3 years) treated in Zagreb University Hospital Center were included. Data collection was based on filling the SURF questionnaire right after the clinical exam or later using review of medical records. Patients were hospitalized because of CABG (1%), PCI (8%), ACS (35%) or chronic stable angina (56%). The history of arterial hypertension had 95%patients (however, on admission mean systolic pressure was 130.1 mmHg, diastolic 76.8 mmHg), 90% had dyslipidaemia (total cholesterol <4.5 mmol/L had 43%; <4.0 mmol/L 33%; LDL-cholesterol <2.5 mmol/L 49%; <2.0 mmol/L 32%; HDL>1.2 mmol/L (women) or >1.0 mmol/L (men) had 67%), 25% had diabetes which was poorly regulated (mean HbA1c 8.2%), 18% were active smokers. After discharge only 24% performed cardiac rehabilitation. Mean body mass index of the patients was 28.3 kg/m2 (32% were obese, 72% overweight). Compared to TASPIC-CRO V there was lower usage of aspirin than recommended on discharge. This was also true for statin therapy. More patients were taking beta blockers, calcium antagonists and diuretics than 7 years ago. This pilot survey showed that CRO-SURF questionnaire is short, quick, effective and simple to use. It is a good and cost effective tool to collect data on CVD risk factors and their management. The results obtained by using it indicate that there is still a high prevalence of modifiable risk factors in Croatian patients with CHD.     

Carotid artery plaque in women with rheumatoid arthritis and low estimated cardiovascular disease risk: a cross-sectional study

IntroductionWe previously reported that most patients with rheumatoid arthritis (RA) and moderate cardiovascular disease (CVD) risk according to the Systematic COronary Evaluation score (SCORE) experience carotid artery plaque. In this study, we aimed to identify patient characteristics that can potentially predict carotid plaque presence in women with RA and a concurrent low CVD risk according to the SCORE.MethodsA cohort of 144 women with an evaluated low risk of CVD (SCORE value of zero) was assembled amongst 550 consecutive patients with RA that underwent CVD risk factor recording and carotid artery ultrasound. Participants had no established CVD, moderate or severe chronic kidney disease, or diabetes. We assessed carotid plaque(s) presence and its associated patient characteristics.ResultsCarotid artery plaque was present in 35 (24.3%) of women with RA. Age, the number of synthetic disease-modifying agents (DMARDs) and total cholesterol concentrations were independently associated with plaque in multivariable stepwise backward regression analysis (odds ratio (95% confidence interval) = 1.15 (1.07 to 1.24), P <0.0001, 1.51 (1.05 to 2.17), P = 0.03 and 1.66 (1.00 to 2.73) P = 0.04), respectively). The area under the curve (AUC) of the receiver operating curve (ROC) for the association with plaque was 0.807 (P <0.0001), 0.679 (P = 0.001) and 0.599 (P = 0.08) for age, total cholesterol concentrations and number of synthetic DMARDs used, respectively. The optimal cutoff value in predicting plaque presence for age was 49.5 years with a sensitivity and specificity of 74% and 75%, respectively, and for total cholesterol concentration, it was 5.4 mmol/l with a sensitivity and specificity of 63% and 70%, respectively. The plaque prevalence was 37.5% in patients (n = 80; 55.6%) with age >49.5 years or/and total cholesterol concentration of >5.4 mmol/l, respectively, compared to only 7.8% in those (n = 64; 44.4%) with age ≤49.5 years or/and total cholesterol concentration of ≤5.4 mmol/l, respectively.ConclusionsApproximately one-third of women with RA who experience a low SCORE value and are aged >49.5 years or/and have a total cholesterol concentration of >5.4 mmol/l, experience high-risk atherosclerosis, which requires intensive CVD risk management.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0576-7) contains supplementary material, which is available to authorized users.     

Cytokine profile, metabolic syndrome and cardiovascular disease risk in women with late-onset gestational diabetes mellitus

Inflammation is an important component of the metabolic syndrome (MetS) which could be the link between the metabolic and the cardiovascular consequences of this condition. Gestational diabetes mellitus (GDM) has been recognized as a significant risk factor for MetS and an inflammation component has been described in this disease. The aim of the study was to evaluate the relationships between cytokine concentrations, components of MetS and cardiovascular risk markers in women with late-onset GDM. Women (n=63) with late-onset GDM and 63 controls were enrolled. Clinical variables, and obstetrics and perinatal outcomes were recorded. Relationships between cytokines (TNF-α, leptin, IL6, adiponectin) and endothelial injury markers (VCAM, ICAM and selectine) were analyzed. Control vs. patient data indicated: pre-gestational body mass index (BMI) 23.46±3.73 vs. 26.97±5.07kg/m(2) (p=0.001); TNF-α 2.2±0.8 vs. 3.1±1.5pg/mL (p=0.002); leptin 18714.78±8859.08 vs. 27365.79±16209.67pg/mL (p=0.001); adiponectin 162.42±34.19 vs. 141.54±41.33ng/mL (p=0.04). Multivariate analyses showed that adiponectin had a protective effect (OR=0.9; p=0.02) and BMI carried a significant risk (OR=8.4; p=0.01) for GDM. No differences were found in endothelial injury markers. In conclusion, the cytokine profile in women with late-onset GDM is characterized by high concentrations of TNF-α and leptin and low adiponectin. This profile is related, in large extent, to an increased pregravid BMI which, potentially, may be linked to the future development of both metabolic and cardiovascular disease.     

Polygenic risk scores in cardiovascular risk prediction: A cohort study and modelling analyses

BackgroundPolygenic risk scores (PRSs) can stratify populations into cardiovascular disease (CVD) risk groups. We aimed to quantify the potential advantage of adding information on PRSs to conventional risk factors in the primary prevention of CVD.Methods and findingsUsing data from UK Biobank on 306,654 individuals without a history of CVD and not on lipid-lowering treatments (mean age [SD]: 56.0 [8.0] years; females: 57%; median follow-up: 8.1 years), we calculated measures of risk discrimination and reclassification upon addition of PRSs to risk factors in a conventional risk prediction model (i.e., age, sex, systolic blood pressure, smoking status, history of diabetes, and total and high-density lipoprotein cholesterol). We then modelled the implications of initiating guideline-recommended statin therapy in a primary care setting using incidence rates from 2.1 million individuals from the Clinical Practice Research Datalink. The C-index, a measure of risk discrimination, was 0.710 (95% CI 0.703–0.717) for a CVD prediction model containing conventional risk predictors alone. Addition of information on PRSs increased the C-index by 0.012 (95% CI 0.009–0.015), and resulted in continuous net reclassification improvements of about 10% and 12% in cases and non-cases, respectively. If a PRS were assessed in the entire UK primary care population aged 40–75 years, assuming that statin therapy would be initiated in accordance with the UK National Institute for Health and Care Excellence guidelines (i.e., for persons with a predicted risk of ≥10% and for those with certain other risk factors, such as diabetes, irrespective of their 10-year predicted risk), then it could help prevent 1 additional CVD event for approximately every 5,750 individuals screened. By contrast, targeted assessment only among people at intermediate (i.e., 5% to <10%) 10-year CVD risk could help prevent 1 additional CVD event for approximately every 340 individuals screened. Such a targeted strategy could help prevent 7% more CVD events than conventional risk prediction alone. Potential gains afforded by assessment of PRSs on top of conventional risk factors would be about 1.5-fold greater than those provided by assessment of C-reactive protein, a plasma biomarker included in some risk prediction guidelines. Potential limitations of this study include its restriction to European ancestry participants and a lack of health economic evaluation.ConclusionsOur results suggest that addition of PRSs to conventional risk factors can modestly enhance prediction of first-onset CVD and could translate into population health benefits if used at scale.

Luanluan Sun and colleagues investigate whether adding polygenic risk scores to conventional risk factors of cardiovascular disease helps predict disease risk.     

Outcome study in liposuction breast reduction

Liposuction as a primary modality of treating breast hypertrophy has been reported in the literature; however, many of these reports are small series and personal experiences. This report is the first outcome study to attempt to validate the effectiveness of liposuction as a primary method of breast reduction surgery. Questionnaires were sent to 117 patients who had undergone liposuction breast reduction surgery in our office during a 4-year period. Seventy-eight questionnaires were returned (67 percent response rate). The patients were asked about their complaints, their surgical results, and their satisfaction with the operation. Complaints such as neck and back pain, shoulder ruts, and intertrigo were improved or eliminated in the vast majority of patients. Women returned to work in 5 days on average and resumed full exercise in 2 weeks. Eighty percent of patients were either very or completely satisfied with their outcomes, 87 percent would choose the liposuction method again, and 92 percent would recommend the liposuction method to a friend. This study demonstrates that liposuction breast reduction is an effective method of breast reduction surgery.     

Pharmacokinetics and safety of lidocaine and monoethylglycinexylidide in liposuction: a microdialysis study

High doses of lidocaine are administered to patients undergoing liposuction. Monoethylglycinexylidide, the active metabolite of lidocaine, is 80 to 90 percent as potent as lidocaine, and its relative toxicity is approximately that of lidocaine. Monoethylglycinexylidide has not previously been measured in studies on lidocaine in liposuction. The aims of this study were to characterize systemic exposure to lidocaine and monoethylglycinexylidide and to measure lidocaine and monoethylglycinexylidide levels within the tissues. Five female volunteers between the ages of 29 and 40 years underwent liposuction. Lidocaine (1577 to 2143 mg, corresponding to 19.9 to 27.6 mg/kg) was infiltrated during the procedure. Levels of lidocaine and monoethylglycinexylidide in blood and lipoaspirate were assessed perioperatively. Tissue lidocaine and monoethylglycinexylidide levels were measured postoperatively using a microdialysis technique in vivo. The peak (maximal) concentration of lidocaine plus monoethylglycinexylidide was 2.2 to 2.7 microg/ml. Time to peak lidocaine plus monoethylglycinexylidide was 8 to 28 hours after infiltration began. Absorbed lidocaine was estimated to be 911 to 1596 mg; therefore, 45 to 93 percent (mean, 64 percent) of the infiltrated dose was ultimately absorbed. Lipoaspirate analysis showed that 9.1 to 10.8 percent (mean, 9.7 percent) of the infiltrated dose was removed during the procedure. Tissue lidocaine levels below 5 microg/ml were demonstrated from 4 to 8 hours postoperatively. The peak lidocaine plus monoethylglycinexylidide concentration was within safe limits in this group of subjects. Time to peak lidocaine plus monoethylglycinexylidide signifies a delayed peak and therefore a longer period of potential lidocaine toxicity than was originally thought. Microdialysis results demonstrated that tissue lidocaine levels may be subtherapeutic within 4 to 8 hours of the procedure. Investigation into factors controlling the resorption of lidocaine during liposuction is warranted in an effort to improve the duration of effect. Furthermore, considering the active metabolite monoethylglycinexylidide, longitudinal studies are necessary to determine whether improving the side effect profile of lidocaine by reducing the dose administered during liposuction may be possible without decreasing the perioperative analgesic effect.     

Postural control deficits in people with fibromyalgia: a pilot study

Introduction  

Postural instability and falls are increasingly recognized problems in patients with fibromyalgia (FM). The purpose of this study was to determine whether FM patients, compared to age-matched healthy controls (HCs), have differences in dynamic posturography, including sensory, motor, and limits of stability. We further sought to determine whether postural instability is associated with strength, proprioception and lower-extremity myofascial trigger points (MTPs); FM symptoms and physical function; dyscognition; balance confidence; and medication use. Last, we evaluated self-reported of falls over the past six months.     

Disease-modifying antirheumatic drugs are associated with a reduced risk for cardiovascular disease in patients with rheumatoid arthritis: a case control study

Rheumatoid arthritis (RA) is characterized by inflammation and an increased risk for cardiovascular disease (CVD). This study investigates possible associations between CVD and the use of conventional disease-modifying antirheumatic drugs (DMARDs) in RA. Using a case control design, 613 RA patients (5,649 patient-years) were studied, 72 with CVD and 541 without CVD. Data on RA, CVD and drug treatment were evaluated from time of RA diagnosis up to the first cardiovascular event or the end of the follow-up period. The dataset was categorized according to DMARD use: sulfasalazine (SSZ), hydroxychloroquine (HCQ) or methotrexate (MTX). Odds ratios (ORs) for CVD, corrected for age, gender, smoking and RA duration, were calculated per DMARD group. Patients who never used SSZ, HCQ or MTX were used as a reference group. MTX treatment was associated with a significant CVD risk reduction, with ORs (95% CI): 'MTX only', 0.16 (0.04 to 0.66); 'MTX and SSZ ever', 0.20 (0.08 to 0.51); and 'MTX, SSZ and HCQ ever', 0.20 (0.08 to 0.54). The risk reductions remained significant after additional correction for the presence of rheumatoid factor and erosions. After correction for hypertension, diabetes and hypercholesterolemia, 'MTX or SSZ ever' and 'MTX, SSZ and HCQ ever' showed significant CVD risk reduction. Rheumatoid factor positivity and erosions both increased CVD risk, with ORs of 2.04 (1.02 to 4.07) and 2.36 (0.92 to 6.08), respectively. MTX and, to a lesser extent, SSZ were associated with significantly lower CVD risk compared to RA patients who never used SSZ, HCQ or MTX. We hypothesize that DMARD use, in particular MTX use, results in powerful suppression of inflammation, thereby reducing the development of atherosclerosis and subsequently clinically overt CVD.