Baseline levels of c‐reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis : A ten‐year followup study of a primary care–based inception cohort

Objective

To test the hypothesis that the C‐reactive protein (CRP) concentration at baseline is an independent predictor of death from cardiovascular disease (CVD) in newly diagnosed patients with inflammatory polyarthritis (IP).

Methods

Patients with IP (n = 506) who were recruited from the Norfolk Arthritis Register between 1990 and 1992 were followed up to the end of 2001, and complete data on mortality were obtained. At baseline, subjects underwent a structured interview and joint examination and completed a Health Assessment Questionnaire (HAQ). Blood was obtained and analyzed for rheumatoid factor (RF) and CRP concentration. Cox regression was used to calculate hazards ratios (HRs) for risk of death from CVD.

Results

The median followup was 10.1 years (interquartile range 9.3–10.8). There were 104 deaths, 40 of which were the result of CVD. Elevated CRP levels (≥5 mg/liter) predicted death from CVD in univariate analyses: HR 3.9 (95% confidence interval [95% CI] 1.2–13.4) for men, and HR 4.22 (95% CI 1.4–12.6) for women. After adjusting for age and sex, the CVD mortality association was strongest in the subgroup of patients who were RF positive at baseline (adjusted HR 7.4 [95% CI 1.7–32.2]). Multivariate analysis revealed that elevated CRP levels remained a significant independent predictor of death from CVD, even after adjusting for age, sex, smoking status, HAQ score, RF positivity, and swollen joint counts (HR 3.3 [95% CI 1.4–7.6]).

Conclusion

The CRP concentration at baseline is an important predictor of subsequent death from CVD in patients with new‐onset IP and is independent of other indicators of disease severity. This supports the theory that CRP may play a direct role in the pathogenesis of CVD.

     

Erosions in inflammatory polyarthritis are symmetrical regardless of rheumatoid factor status: results from a primary care-based inception cohort of patients

BACKGROUND AND AIMS: Symmetry is considered an important criterion for the differentiation of rheumatoid arthritis (RA) from other forms of inflammatory polyarthritis (IP), particularly those that are seronegative. Because of the inclusion of symmetry in the diagnostic and classification process, however, its true occurrence in RA cannot be assessed. As a surrogate, peripheral inflammatory arthropathies associated with rheumatoid factor production may be more likely to be symmetrical. We examined the degree of symmetry of erosions in an unselected cohort of patients with IP and tested the hypothesis that the presence of rheumatoid factor (RF) is associated with greater symmetry. METHODS: All patients registered with The Norfolk Arthritis Register (NOAR; a UK primary-care based cohort of patients with IP with annual follow-up) and who had radiographs performed at the fifth anniversary from notification were included in the analysis. Radiographs of the hands and feet were read using the Larsen method; a score of 2 or more in any particular joint indicated an erosion. Log-linear modelling was used to determine the symmetry of erosions between right and left for the following joint groups: wrists, metacarpophalangeal joints, proximal interphalangeal joints and metatarsophalangeal joints. Log-linear modelling was also used to determine the influence of RF on symmetry. RESULTS: Five hundred and thirty-seven patients contributed to the analysis. The median time to performing radiographs was 69 months (interquartile range 65.5-74.8) from the onset of symptoms. A total of 212 (39%) patients had erosive disease. Overall, IP was found to be a symmetrical disease. Despite there being more erosions in RF-positive patients, there was no greater excess of symmetry in RF-positive compared with RF-negative patients. CONCLUSION: Radiographically, IP is a symmetrical disease irrespective of RF status. The use of symmetry as an important feature in identifying subgroups of patients with IP, such as RA, is challenged.     

Five-year outcome of a primary-care-based inception cohort of patients with inflammatory polyarthritis plus psoriasis

OBJECTIVES: To establish whether patients with inflammatory arthritis plus psoriasis have a different outcome from those who do not have psoriasis. METHODS: Seventy-nine patients with inflammatory arthritis plus psoriasis were recruited by the Norfolk Arthritis Register (NOAR) in 1990-94 and followed for 5 yrs. Their outcome was compared with the remainder (n = 755) of the NOAR cohort. We then restricted the analysis to subjects who were rheumatoid factor (RF)-negative, and compared those with and without psoriasis. Outcomes studied included remission, deformed joint count, the presence and extent of erosive damage and physical function. RESULTS: Patients with psoriasis were younger, more likely to be male, less likely to be RF-positive and more likely to have been treated with disease-modifying drugs than patients without psoriasis. After adjustment for age, gender and treatment, the only differences between the psoriasis and non-psoriasis groups were in RF positivity (adjusted odds ratio 0.44; 95% CI 0.25, 0.78) and in the Larsen score in patients with erosions. CONCLUSIONS: Patients with inflammatory arthritis plus psoriasis have a similar outcome to other RF-negative patients with arthritis.     

C-reactive protein in the prediction of cardiovascular and overall mortality in middle-aged men: a population-based cohort study

Aims Cut-offs for C-reactive protein concentrations have beenrecommended for risk stratification, but little is known abouthow these cut-offs predict cardiovascular risk in population-basedcohorts. We therefore assessed the association of C-reactiveprotein levels with cardiovascular mortality in a population-basedcohort of 2321 middle-aged men stratified by the presence ofcardiovascular disease (CVD) at baseline. Methods and results C-reactive protein concentrations were categorizedaccording to current recommendations (1 and 3 mg/L). Duringthe 15 year follow-up, 77 men without CVD and 121 men with CVDat baseline died of CVD. In men without CVD at baseline (n=1476),age-adjusted cardiovascular mortality was 4.1-fold higher (95%CI 2.1–8.2) for C-reactive protein levels between 3.0and 9.9 mg/L at baseline than for C-reactive protein levels<1.0 mg/L. In men with CVD at baseline (n=845), thecorresponding age-adjusted cardiovascular mortality was 3.3-foldhigher (95% CI 2.0–5.3). Adjustment for conventional CVDrisk factors attenuated the risk somewhat. Further adjustmentfor dietary and lifestyle factors and factors related to insulinresistance did not affect the association. Classification ofC-reactive protein by tertiles gave qualitatively similar results,but identified twice as many men at high risk. C-reactive proteinlevels also predicted overall mortality. Conclusion Currently, recommended cut-offs for C-reactive proteinlevels identify men at risk for cardiovascular and overall deathindependently of conventional and other risk factors in a population-basedsample of middle-aged men with and without CVD at baseline.Lower cut-offs may better identify men at high risk for cardiovasculardeath, but improvement of current recommendations will requirestandardization of C-reactive protein assays.     

High ten-year risk of cardiovascular disease in newly diagnosed rheumatoid arthritis patients: a population-based cohort study

OBJECTIVE: To estimate the 10-year absolute risk of cardiovascular (CV) events in newly diagnosed rheumatoid arthritis (RA) patients and the potential contribution of CV risk factors to absolute risk assessment. METHODS: A population-based incidence cohort of RA patients (defined according to the American College of Rheumatology 1987 criteria) was assembled and compared with an age- and sex-matched non-RA cohort. Data were collected on CV risk factors and CV events. Cox regression models were used to estimate the 10-year risk of a combined CV end point, adjusting for CV risk factors. Subjects were classified into 5 risk categories based on their 10-year absolute risk. RESULTS: The absolute CV risk in RA patients was similar to that in non-RA subjects who were 5-10 years older. The absolute risk varied substantially according to the presence of CV risk factors. The 10-year absolute CV risk among 60-69-year-old RA patients with no risk factors was 16.8%, but rose to 60.4% if risk factors such as smoking, hypertension, dyslipidemia, diabetes, and obesity were present. Among RA patients with a low body mass index, in addition to the above risk factors, the 10-year absolute CV risk rose to 86.2%. CONCLUSION: More than half of the newly diagnosed RA patients who were 50-59 years of age and all of those >60 years of age had a >10% risk of CV disease within 10 years of their RA incidence and should be targeted for specific CV risk reduction strategies tailored to their personal risk profiles.     

Association of the HLA-DRB1 gene with premature death, particularly from cardiovascular disease, in patients with rheumatoid arthritis and inflammatory polyarthritis

OBJECTIVE: To examine the role of the variants of the PTPN22 and HLA-DRB1 genes as predictors of mortality in inflammatory polyarthritis (IP) and rheumatoid arthritis (RA). METHODS: Patients were recruited from a primary care-based inception cohort of patients with IP and were followed up prospectively. For patients who died, the cause and date of death was obtained. Cox proportional hazards regression models were used to assess the association of the HLA-DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti-cyclic citrullinated peptide (anti-CCP) status, adjusted by age at symptom onset and sex. RESULTS: DNA samples were available from 1,022 IP patients. During followup, 751 of them (74%) satisfied the American College of Rheumatology 1987 criteria for RA, and 242 of them (24%) died. Carriage of 2 copies of SE alleles predicted death from all causes (hazard ratio [HR] 1.57 [95% confidence interval (95% CI) 1.1-2.2]) and from CVD (HR 1.68 [95% CI 1.1-2.7]). This effect was most marked for individuals with the HLA-DRB1*01/*04 combination. An interaction of smoking, SE alleles, and anti-CCP antibodies was observed and was associated with the greatest risk of death from CVD (HR 7.81 [95% CI 2.6-23.2]). No association of the PTPN22 gene with mortality was detected. CONCLUSION: SE alleles, particularly compound heterozygotes, are associated with death from all causes and from CVD, independently of autoantibody status. However, the combination of SE, smoking, and anti-CCP antibodies is associated with a high risk of premature death in patients with IP and RA, which raises the possibility of a targeted strategy to prevent CVD in these patients.     

Complementary and alternative medicine in patients with inflammatory bowel disease: The results of a population-based inception cohort study (IBSEN)

Background and aimsThe use of complementary and alternative medicine (CAM) has been increasing in recent decades. Our aim was to determine the proportion of CAM use among patients with inflammatory bowel disease (IBD) in a longitudinal, population-based cohort and to identify predictive factors for CAM use.MethodsThe Inflammatory Bowel South-Eastern Norway (IBSEN) study is a population-based IBD cohort that has been followed prospectively for 10 years. The ten-year follow-up was conducted from 2000 to 2004 and included a questionnaire regarding CAM, a structured interview, a review of hospital records, a clinical examination, laboratory tests, and an ileocolonoscopy.ResultsOf the 620 patients evaluated at the ten-year follow-up, 517 (84%) completed the CAM questionnaire, 353 had ulcerative colitis (UC), 164 had Crohn's disease (CD), and 50% were male. Thirty percent reported the use of CAM at some point since their IBD diagnosis, and 7.5% reported current CAM use. More CD patients than UC patients reported CAM use (38% vs. 27%, respectively; p = 0.01). Younger age, female gender, and higher education level predicted CAM use in UC, whereas younger age was the only predictor of CAM use in CD. Thirty-six percent of the CAM users were mostly satisfied or very satisfied with the treatment.ConclusionOne third of the patients in this population-based cohort had used CAM at some point during a ten-year disease course, but only 7.5% reported current CAM use. CAM use was more common in the CD than in the UC patients. Only socio-demographic factors, such as age, gender and education, predicted CAM use.     

Ethnic differences in inflammatory bowel disease: Results from the United Kingdom inception cohort epidemiology study

BACKGROUND The current epidemiology of inflammatory bowel disease(IBD) in the multiethnic United Kingdom is unknown. The last incidence study in the United Kingdom was carried out over 20 years ago.AIM To describe the incidence and phenotype of IBD and distribution within ethnic groups.METHODS Adult patients( 16 years) with newly diagnosed IBD(fulfilling Copenhagen diagnostic criteria) were prospectively recruited over one year in 5 urban catchment areas with high South Asian population. Patient demographics, ethnic codes, disease phenotype(Montreal classification), disease activity and treatment within 3 months of diagnosis were recorded onto the Epicom database.RESULTS Across a population of 2271406 adults, 339 adult patients were diagnosed with IBD over one year: 218 with ulcerative colitis(UC, 64.3%), 115 with Crohn's disease(CD, 33.9%) and 6 with IBD unclassified(1.8%). The crude incidence of IBD, UC and CD was 17.0/100000, 11.3/100000 and 5.3/100000 respectively. The age adjusted incidence of IBD and UC were significantly higher in the Indian group(25.2/100000 and 20.5/100000) compared to White European(14.9/100000,P = 0.009 and 8.2/100000, P 0.001) and Pakistani groups(14.9/100000, P = 0.001 and 11.2/100000, P = 0.007). The Indian group were significantly more likely to have extensive disease than White Europeans(52.7% vs 41.7%, P = 0.031). There was no significant difference in time to diagnosis, disease activity and treatment.CONCLUSION This is the only prospective study to report the incidence of IBD in an ethnically diverse United Kingdom population. The Indian ethnic group showed the highest age-adjusted incidence of UC(20.5/100000). Further studies on dietary,microbial and metabolic factors that might explain these findings in UC are underway.     

Serum C-reactive protein levels and death and cardiovascular events in mild to moderate chronic kidney disease

Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular (CV) disease. Elevated circulating levels of high sensitivity C-reactive protein (hsCRP) have been suggested to be associated with high risk of CV disease. It is uncertain whether the CV risk in CKD can be stratified by hsCRP levels in the Japanese population. Baseline data including serum hsCRP and creatinine levels were determined in the general population. Estimated glomerular filtration rate (eGFR) was calculated using a modified MDRD equation, and CKD was defined as eGFR below 60 mL/minute/1.73m(2). We analyzed 1,074 male subjects with mild to moderate CKD (mean age, 70.4 years). CV events (stroke and myocardial infarction) and all-cause death were surveyed prospectively. The CKD subjects were followed for 5.1 years, and 72 CV events and 115 all-cause deaths were found (composite endpoint). After adjustment for established CV risk factors, hazard ratios (HRs) for the endpoint were significantly increased according to the hsCRP quintile (P < 0.001), and HR for the highest (versus the lowest) quintile was 2.77 (95% CI; 1.61-4.77). These results suggest that serum hsCRP measurement is a useful tool for the risk stratification of CV events and death in CKD male subjects selected from the general population.     

Health care and patients' education in a European inflammatory bowel disease inception cohort: An ECCO-EpiCom study

Background and AimsThe EpiCom study and inception cohort was initiated in 2010 in 31 centers from 14 Western and 8 Eastern European countries, covering a 10.1 million person background population. Our aim was to investigate whether there is a difference between Eastern and Western Europe in health care and education of patients with inflammatory bowel disease (IBD).MethodsA quality of care (QoC) questionnaire was developed in the EpiCom group consisting of 16 questions covering 5 items: time interval between the onset of symptoms and diagnosis, information, education, empathy and access to health care providers.ResultsOf 1,515 patients, 947 (217 east/730 west) answered the QoC questionnaire. Only 23% of all patients had knowledge about IBD before diagnosis. In Eastern Europe, significantly more patients searched out information about IBD themselves (77% vs. 68%, p < 0.05), the main source was the Internet (92% vs. 88% p = 0.23). In Western Europe, significantly more patients were educated by nurses (19% vs. 1%, p < 0.05), while in Eastern Europe, gastroenterologists were easier to contact (80% vs. 68%, p < 0.05).ConclusionHealth care differed significantly between Eastern and Western Europe in all items, but satisfaction rates were high in both geographic regions. Because of the low awareness and the rising incidence of IBD, general information should be the focus of patient organizations and medical societies. In Western Europe IBD nurses play a very important role in reducing the burden of patient management.     

Environmental factors in inflammatory bowel disease: A case-control study based on a Danish inception cohort

Background

The role of environmental factors in development of inflammatory bowel disease (IBD) remains uncertain. The aim of the present study was to assess a number of formerly suggested environmental factors in a case-control study of an unselected and recently diagnosed group of patients with IBD and a control group of orthopaedic patients.

Methods

A total of 123 patients diagnosed with Crohn's disease (CD) and 144 with ulcerative colitis (UC) in Copenhagen (2003–2004) were matched 1:1 on age and gender to 267 orthopaedic controls. Participants received a questionnaire with 87 questions concerning environmental factors prior to IBD/orthopaedic admission. Odds ratios (OR) were calculated by logistic regression.

Results

Being breastfed > 6 months (OR, 0.50; 95% CI, 0.23–1.11) and undergoing tonsillectomy (OR, 0.49; 95% CI, 0.31–0.78) decreased the odds for IBD, whereas appendectomy decreased the odds for UC only (OR, 0.29; 95% CI, 0.12–0.71). Vaccination against pertussis (OR, 2.08; 95% CI, 1.07–4.03) and polio (OR, 2.38; 95% CI, 1.04–5.43) increased the odds for IBD, whereas measles infection increased the odds for UC (OR, 3.50; 95% CI, 1.15–10.6). Low consumption of fibres and high consumption of sugar were significantly associated with development of CD and UC. Smoking increased the risk for CD and protected against UC.

Conclusion

Among Danish patients with CD and UC belonging to an unselected cohort, disease occurrence was found to be associated both with well-known factors such as smoking and appendectomy, and with more debated factors including breastfeeding, tonsillectomy, childhood vaccinations, childhood infections, and dietary intake of fibres and sugar.     

A randomized trial of a primary care-based disease management program to improve cardiovascular risk factors and glycated hemoglobin levels in patients with diabetes

PURPOSE: To assess the efficacy of a pharmacist-led, primary care-based, disease management program to improve cardiovascular risk factors and glycated hemoglobin (A(1C)) levels in vulnerable patients with poorly controlled diabetes. METHODS: A randomized controlled trial of 217 patients with type 2 diabetes and poor glycemic control (A(1C) level >or=8.0%) was conducted at an academic general medicine practice from February 2001 to April 2003. Intervention patients received intensive management from clinical pharmacists, as well as from a diabetes care coordinator who provided diabetes education, applied algorithms for managing glucose control and decreasing cardiovascular risk factors, and addressed barriers to care. Control patients received a one-time management session from a pharmacist followed by usual care from their primary care provider. Outcomes were recorded at baseline and at 6 and 12 months. Primary outcomes included blood pressure, A(1C) level, cholesterol level, and aspirin use. Secondary outcomes included diabetes knowledge, satisfaction, use of clinical services, and adverse events. RESULTS: For the 194 patients (89%) with 12-month data, the intervention group had significantly greater improvement than did the control group for systolic blood pressure (-9 mm Hg; 95% confidence interval [CI]: -16 to -3 mm Hg) and A(1C) level (-0.8%; 95% CI: -1.7% to 0%). Change in total cholesterol level was not significant. At 12 months, aspirin use was 91% in the intervention group versus 58% among controls (P <0.0001). Intervention patients had greater improvements in diabetes knowledge and satisfaction than did control patients. There were no significant differences in use of clinical services or adverse events. CONCLUSION: Our comprehensive disease management program reduced cardiovascular risk factors and A(1C) levels among vulnerable patients with type 2 diabetes and poor glycemic control.     

C-reactive protein and cardiovascular disease: a critical appraisal

PURPOSE OF REVIEW: C-reactive protein, a nonspecific marker of inflammation, has recently been proposed both as a marker of low-grade inflammation involved in atherogenesis and as a predictor of disease progression. RECENT FINDINGS: The physiologic functions of C-reactive protein as an anti-inflammatory scavenger molecule have begun to emerge. For example, C-reactive protein binds to damaged lipoproteins and facilitates their removal by phagocytes without full complement activation. Increased levels of C-reactive protein may result in direct effects on vascular cells, including induction of cytokines and prothrombotic factors. Several sources of biologic variation in the levels of C-reactive protein have been identified, chief among which are abdominal obesity and the metabolic syndrome. Although previous studies showed a potent independent association of C-reactive protein levels with cardiac events, the strength of association was shown to be much weaker than previously reported in recent large meta-analyses. Therapy with nonspecific anti-inflammatory agents such as statins in patients with coronary artery disease has been found to reduce adverse outcomes in association with reductions in C-reactive protein, on the basis of retrospective analysis of stored blood specimens. SUMMARY: Despite a relatively strong epidemiologic association with future adverse cardiovascular events, the great majority of apparently healthy individuals with elevated C-reactive protein will not experience cardiovascular disease. Even though more than 15 000 articles in PubMed mention C-reactive protein, current knowledge is insufficient to implicate C-reactive protein as a causative factor in atherothrombosis or to enable the recommendation of C-reactive protein testing to guide preventive or therapeutic interventions in cardiovascular diseases.     

Narrative review: Assessment of C-reactive protein in risk prediction for cardiovascular disease

Some experts propose C-reactive protein (CRP) as a screening tool for prediction of cardiovascular disease (CVD). Many epidemiologic studies show positive associations between elevated CRP levels and incident CVD. Assessment of the value of new prognostic tests, however, must rely on understanding of test characteristics rather than on associations measured by relative risks. In the case of CRP, test characteristics must be judged in the context of currently available CVD risk prediction algorithms. In this review of literature published before January 2006, the authors describe what is known about the additional utility of CRP in risk prediction. They find no definitive evidence that, for most individuals, CRP adds substantial predictive value above that provided by risk estimation using traditional risk factors for CVD. Use of CRP may add to risk estimation in a limited subset of individuals who are at intermediate predicted risk according to the Framingham risk score. The authors propose that many questions still must be addressed before CRP is incorporated into risk prediction algorithms and before universal screening with CRP can be recommended.     

Communication of information to patients with inflammatory bowel disease: A European Collaborative Study in a multinational prospective inception cohort

Background and aimsCommunication to patients of information about their disease has become increasingly important in modern medicine, and particularly with chronic nonfatal disorders like inflammatory bowel disease (IBD), but the subject is not adequately researched or understood.MethodsWe studied the media and preferences for communication of information in a multi-national community-based inception cohort of European and Israeli patients with IBD and 10 years follow-up, using structured questionnaires categorizing demographics, disease status, current and preferred sources of information, use of electronic media, role of patients' associations, and satisfaction level.ResultsThe 917 patients completing the questionnaire were derived from northern (60%) and southern (40%) countries. The mean age was 48.3 years (62% under 50 years); 51% were males; 67% had ulcerative colitis, 33% Crohn's disease. Sixty-six percent of patients designated the specialist as their primary source of information, 77% indicated satisfaction with their current information, and 65% reported not receiving information about medical treatment in the past year. Patient concerns were about new research into their illness (64%), medical treatments (58%), risks and complications (51%) and genetics (42%). Preferred sources of information were paper bulletin (76%), electronic media (30%) and international organization (79%). Diagnosis (ulcerative colitis or Crohn's disease), gender, education level and country impacted significantly on patients' choices.ConclusionsIn providing health care information to patients with IBD their individual attitudes and preferences must be considered. There should be greater roles for IBD patients' associations and international IBD-research organizations, and an increasing use of electronic media.     

Association of the HLA–DRB1 gene with premature death,particularly from cardiovascular disease,in patients with rheumatoid arthritis and inflammatory polyarthritis

Objective

To examine the role of the variants of the PTPN22 and HLA–DRB1 genes as predictors of mortality in inflammatory polyarthritis (IP) and rheumatoid arthritis (RA).

Methods

Patients were recruited from a primary care–based inception cohort of patients with IP and were followed up prospectively. For patients who died, the cause and date of death was obtained. Cox proportional hazards regression models were used to assess the association of the HLA–DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti–cyclic citrullinated peptide (anti‐CCP) status, adjusted by age at symptom onset and sex.

Results

DNA samples were available from 1,022 IP patients. During followup, 751 of them (74%) satisfied the American College of Rheumatology 1987 criteria for RA, and 242 of them (24%) died. Carriage of 2 copies of SE alleles predicted death from all causes (hazard ratio [HR] 1.57 [95% confidence interval (95% CI) 1.1–2.2]) and from CVD (HR 1.68 [95% CI 1.1–2.7]). This effect was most marked for individuals with the HLA–DRB1*01/*04 combination. An interaction of smoking, SE alleles, and anti‐CCP antibodies was observed and was associated with the greatest risk of death from CVD (HR 7.81 [95% CI 2.6–23.2]). No association of the PTPN22 gene with mortality was detected.

Conclusion

SE alleles, particularly compound heterozygotes, are associated with death from all causes and from CVD, independently of autoantibody status. However, the combination of SE, smoking, and anti‐CCP antibodies is associated with a high risk of premature death in patients with IP and RA, which raises the possibility of a targeted strategy to prevent CVD in these patients.

     

Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease

The polycystic ovary syndrome (PCOS), one of the most common reproductive abnormalities, shares some components of the metabolic cardiovascular syndrome. Therefore, PCOS patients may represent the largest group of women at high risk for the development of early-onset cardiovascular disease (CVD) and/or diabetes. C-reactive protein (CRP) is a strong independent predictor of future CVD and/or stroke. Only one small published study has looked for such an association (17 PCOS patients vs. 15 controls). The objective of this study was to compare the levels of CRP and other risk factors of CVD in a large group of PCOS patients and controls. CRP measurements were undertaken in 116 PCOS patients and 94 body mass index-matched controls with regular menstrual cycles. Whereas 36.8% of the PCOS patients had CRP levels above 5 mg/liter, only 9.6% of the controls exhibited high CRP levels (P < 0.001). The mean +/- SD was 5.46 +/- 7.0 in the PCOS group vs. 2.04 +/- 1.9 mg/liter in the control (P < 0.001). The body mass index, white blood cell count, TSH, glucose, cholesterol, and homocysteine levels were not significantly different between the two groups. CRP levels are elevated in patients with PCOS and may be a marker of early cardiovascular risk in these patients. High CRP levels may explain why some PCOS women may possibly be at an increased risk for the development of early-onset CVD. Consequently, whether treatment regimens directed toward lowering CVD risk factors should be more aggressive for those PCOS women with increased CRP levels, awaits further clinical experience.