Traditional Cardiovascular Risk Factors Increase, Treatments Reduce Heart Attack Risk in People
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Traditional Cardiovascular Risk Factors Increase, Treatments Reduce Heart Attack Risk in People with Rheumatoid Arthritis
Age, sex and traditional risk factors—such as hypertension, diabetes, smoking, and body mass—are more important predictors of heart attack in patients with rheumatoid arthritis than the use of certain medications that have been considered the link between the two and lipid-lowering medications may actually reduce this risk, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in San Francisco, Calif.
Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.
Disease-modifying antirheumatic drugs, or DMARDS as they are commonly called, are often the therapy of choice for patients with RA as they not only reduce inflammation and pain, but can slow the overall progression of the disease.
Although it is known that people with RA are at an increased risk for premature death due to heart attacks, little is known about the influence of RA disease activity, the use of DMARD and corticosteroid therapy, and the impact of traditional cardiovascular risk factors on the development of heart disease in people with RA. It is uncertain what effect reducing risk factors like high blood fat and cholesterol levels or high blood pressure has on heart disease risk in these patients.
Researchers in the United Kingdom, in two studies, recently looked to the United Kingdom General Practice Research Database, or GPRD, which contains the records of over seven million individuals—including patients with RA—to estimate the incidence of heart attack and assess whether DMARDS and corticosteroid therapy played a role in heart attack. They also evaluated the effectiveness of lipid-lowering medications and antihypertensive drugs in the prevention of heart attacks in patients diagnosed with RA.
The GPRD was used to identify 34,364 adults with RA and 103,089 controls – all of whom were matched according to age, sex, and primary care practice. The subjects were studied between 1987 and 2002, and the incidence of heart attack in those with RA was compared to that in the controls.
Researchers documented 2.96 heart attacks per 1,000 people each year in the control group and 6.49 per 1,000 people per year among patients with RA.
In the first study, researchers found that of the 966 cases of heart attack occurring in patients with RA, 73 percent of the cases, patients had taken a DMARD or prednisolone (a cortisone drug) at some point during the study period prior to the heart attack, and in 56 percent of the cases, patients had taken a DMARD or prednisolone in the two months immediately prior to the heart attack.
The chance of having a heart attack among patients with RA who had been prescribed a DMARD or prednisolone was reduced compared to the chance of heart attack in patients who had not been prescribed either of these. When analyzing DMARDS separately, researchers found that the use of hydroxycholoroquine, methotrexate, and sulphasalazine appeared to be protective against heart attack in these patients, while prednisolone was found to increase the risk but these effects were modest compared to traditional risk factors
In the second study, researchers found that treatment with lipid-lowering medications were associated with a significant reduction in the incidence of heart attacks among the patients studied – dropping the incidence rate by 25 percent.
However, when researchers looked at the effect that traditional risk factors have on heart attacks, they found that although these factors were important, the effect of having RA itself was greater.
“This suggests that treating RA and traditional cardiovascular risk factors, such as high cholesterol, are both important in trying to reduce the number of heart attacks in our patients with RA,” explains Christopher J. Edwards, BSc, FRCP, MD; consultant rheumatologist and honorary senior lecturer, Southampton General Hospital, department of rheumatology, Southampton, United Kingdom, and lead investigator in both studies. “We have known for a while that RA is associated with an increased risk of heart attacks. This work gives an insight into the relative importance of different risk factors in this process. The presence of RA appears to be the most important factor, followed by traditional cardiovascular risk factors and then prednisolone use. Importantly, the use of treatments to lower cholesterol may reduce this risk.”
The ACR is an organization of and for physicians, health professionals, and scientists that advances rheumatology through programs of education, research, advocacy and practice support that foster excellence in the care of people with or at risk for arthritis and rheumatic and musculoskeletal diseases. For more information on the ACR’s annual meeting, see http://www.rheumatology.org/annual.
Editor’s Notes: Dr. Edwards will present “Myocardial Infarction in Rheumatoid Arthritis: The Effects of Traditional Risk Factors, Anti-Hypertensive and Lipid-lowering medication” during the ACR Annual Scientific Meeting at the Moscone Center from 5:15 – 5:30 PM on Sunday, October 26, in Room 307 and will present “Myocardial Infarction in Rheumatoid Arthritis: The Effects of DMARDs and Prednisolone” from 5:30 – 5:45 PM in the same session. Dr. Edwards will be available for media questions and briefing at 8:30 AM on Sunday, October 26 in the on-site press conference room, 114.
Presentation Number: 688
Myocardial Infarction in Rheumatoid Arthritis: The Effects of DMARDs and Prednisolone
Christopher J. Edwards1, David Fisher2, Tjeerd van Staa3, Cyrus Cooper2, Nigel Arden2. 1Southampton University Hospitals NHS Trust, Southampton, United Kingdom; 2MRC Epidemiology Resource Centre, University of Southampton, Southampton, United Kingdom; 3Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
Objectives: Individuals with rheumatoid arthritis (RA) have an increased risk of premature death due to ischaemic heart disease (IHD). However, the relative importance of RA disease acitivity, DMARD/corticosteroid therapy and traditional cardiovascular risk factors in this process is unclear. We investigated a large population based database to estimate the incidence of myocardial infarction (MI) in individuals diagnosed with RA and estimate the contribution of DMARD/corticosteroid therapy.
Methods: The United Kingdom General Practice Research Database (GPRD) contains the records of 7 million individuals. The GPRD was used to identify adults with RA and three age and sex and practice matched controls. Subjects were studied between 1987 and 2002. The incidence of MI in RA compared to controls was calculated and the effect of traditional cardiovascular risk factors estimated.
Results: 34,364 RA patients were identified along with 103,089 controls (3 per case) matched for age, sex and GP practice. The incidence of MI was 2.96 (95% CI 2.81,3.13) per 1000 person-years for the control and 6.49 (95% CI 5.98,7.02) per 1000 person-years in the RA population. Using Poisson regression the incident rate ratio (IRR) was increased for MI by a diagnosis of RA (2.23 (95% CI 2.07, 2.41) (p<0.001)). Of the 966 cases of MI occurring in RA patients (73%; N=705) received a DMARD or prednisolone during the study period (prior to the MI) with 56% (N=538) receiving a DMARD or prednisolone in the 2 months immediately prior to the MI. Using Poisson regression, the IRR for MI among RA cases on a DMARD or prednisolone prescription compared to on no prescription was 0.94 (95% CI 0.83 to 1.07; p=0.3). When analysing DMARD’s separately, it was found that hydroxycholoroquine (IRR vs no drug=0.42, p=0.03), methotrexate (IRR vs no drug=0.67, p=0.03) and sulphasalazine (IRR vs no drug =0.69, p=0.004) were each protective against MI among RA cases, whereas prednisolone increased the risk (IRR vs no drug=1.49, p<0.001). After adjustment for potential confounders (age, sex, BMI, hypertension, diabetes, smoking) the effect sizes remained similar, but were no longer significant (IRR=0.39, p=0.1; IRR=0.86, p=0.5; IRR=0.84, p=0.3 and IRR=1.16, p=0.2 respectively).
Conclusions: Individuals with RA have an increased risk of MI. Overall, age, sex and traditional risk factors were more important predictors of MI than DMARDs and prednisolone use. DMARDs including hydroxycholoroquine, methotrexate and sulphasalazine may reduce the risk and prednisolone increase the risk of MI in individuals with RA.
Disclosure Block: C.J. Edwards, None; D. Fisher, None; T. van Staa, None; C. Cooper, None; N. Arden, None.
Presentation Number: 687
Myocardial Infarction in Rheumatoid Arthritis: The Effects of Traditional Risk Factors, Anti-Hypertensive and Lipid-lowering medication
Christopher J. Edwards1, David Fisher2, Tjeerd van Staa3, Cyrus Cooper2, Nigel Arden2. 1Southampton University Hospitals NHS Trust, Southampton, United Kingdom; 2MRC Epidemiology Resource Centre, University of Southampton, Southampton, United Kingdom; 3Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, Netherlands
Objectives: Individuals with rheumatoid arthritis (RA) have an increased risk of premature death due to ischaemic heart disease (IHD). However, the relative importance of RA disease acitivity, DMARD/corticosteroid therapy and traditional cardiovascular risk factors in this process is unclear. The benefits of altering traditional risk factors with lipid-lowering drugs and anti-hypertensives are also uncertain. We investigated a large population based database to estimate the incidence of myocardial infarction (MI) in individuals diagnosed with RA and estimate the importance of traditional risk factors and their treatments.
Methods: The United Kingdom General Practice Research Database (GPRD) contains the records of 7 million individuals. The GPRD was used to identify adults with RA and three age and sex and practice matched controls. Subjects were studied between 1987 and 2002. The incidence of MI in RA compared to controls was calculated and the effect of traditional cardiovascular risk factors estimated.
Results: 34,364 RA patients were identified along with 103,089 controls (3 per case) matched for age, sex and GP practice. The incidence of MI was 2.96 (95% CI 2.81,3.13) per 1000 person-years for the control and 6.49 (95% CI 5.98,7.02) per 1000 person-years in the RA population. Using Poisson regression the incident rate ratio (IRR) was increased for MI by a diagnosis of RA (2.23 (95% CI 2.07, 2.41) (p<0.001)). The effect remained when adjusted for for age, sex, hypertension, diabetes, smoking, BMI, anti-hypertensive drugs, lipid-lowering drugs and DMARDs/prednisolone use. BMI did not produce a significant effect on the rate ratio of MI. Treatment with lipid-lowering drugs produced a significant reduction in the incident rate ratio of MI (0.75 (95%CI 0.62, 0.90)(p=0.003)). Treatment with anti-hypertensives (adjusted for hypertension) had no significant effect (0.92 (0.84, 1.00)(p=0.062).
Conclusions: Individuals with RA have an increased risk of MI that remains after adjusting for traditional risk factors. Lipid-lowering medications produce a significant reduction in this risk.
Disclosure Block: C.J. Edwards, None; D. Fisher, None; T. van Staa, None; C. Cooper, None; N. Arden, None.
Source: American College of Rheumatology (ACR)
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