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Biomedical subjects

Carolyn C Cannuscio

Publications and source records attributed to Carolyn C Cannuscio.

11 recordsLinked to original sources

Cardiovascular risk of selective cyclooxygenase-2 inhibitors and other non-aspirin non-steroidal anti-inflammatory medications.

PURPOSE: The purpose of this study was to estimate rates of acute coronary syndrome (ACS), and sudden cardiac death in relation to use of rofecoxib, celecoxib, naproxen, diclofenac, and ibuprofen. METHODS: We conducted a retrospective cohort study among 424,584 health plan enrollees ages 40-64 who used non-aspirin non-steroidal anti-inflammatory drugs (NANSAIDs) by prescription from 1999 to 2001. We used automated medical and pharmacy claims data to compute person-time exposed to study drugs, and to identify hospitalizations for ACS. The primary endpoint was ACS, inclusive of myocardial infarction (MI), unstable angina, and sudden cardiac death as identified through claims data and confirmed through hospital medical records, or through the National Death Index. RESULTS: Compared with ibuprofen or diclofenac use, the relative risk (RR) of ACS during periods of current rofecoxib use was 1.35 (95%CI 1.09-1.68). For current use of celecoxib, the RR was 1.03 (95%CI 0.83-1.27). Risks in the first 30 days of rofecoxib and celecoxib use were modestly elevated. Rofecoxib use at the 25 mg/day (modal) dose was associated with an elevated risk of ACS (RR 1.54, 95%CI 1.15-2.04), while use at 26-50 mg/day (>modal) was not (RR 0.81, 95%CI 0.41-1.60). There were no increased risks with modal or greater than modal doses of celecoxib or naproxen compared with all doses of ibuprofen or diclofenac combined. CONCLUSIONS: The incidence of ACS was 1.35 times greater during rofecoxib use than use of ibuprofen or diclofenac. No statistically significant elevation in risk was observed with celecoxib use. Naproxen use was not associated with risk of ACS.

Acute Disease↗

Polymorphisms in the CC-chemokine receptor-2 (CCR2) and -5 (CCR5) genes and risk of coronary heart disease among US women.

OBJECTIVE: Genetic variation in CC-chemokine receptor-2 (CCR2) and -5 (CCR5), and their common haplotypes, acting through inflammatory responses, may affect atherosclerosis and risk of coronary heart disease (CHD). METHOD AND RESULTS: We examined seven common variants in the CCR2 and CCR5 loci and risk of CHD among women in the Nurses' Health Study. During 8 years of follow-up, we documented 248 incident cases of nonfatal myocardial infarction and fatal CHD, and matched controls 2:1 based on age and smoking. The distribution of alleles was similar between cases and controls. The haplotype-specific odds ratios (ORs) were not statistically significant nor was the globally-adjusted p-value (p=0.61). However, there was a statistically significant association for CCR5-Delta32 and A58755G (rs2856758) between cases and controls comparing age of onset <55 and >or=55 years. For Delta32, the OR for having the variant was 0.12 (0.02-0.76) for age <55, and 1.14 (0.69-1.88) for age >or=55 years (p, interaction=0.04). The CCR5-Delta32 was in linkage disequilibrium with 58755G, and a similar association was observed for having the 58755G. CONCLUSIONS: In this population, CCR2-CCR5 haplotypes were not associated with risk of CHD. However, our data suggest a strong inverse association for certain CCR5 variants and early age of CHD onset.

Adult↗

Inflammatory markers and the risk of coronary heart disease in men and women.

BACKGROUND: Few studies have simultaneously investigated the role of soluble tumor necrosis factor alpha (TNF-alpha) receptors types 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein, and interleukin-6 as predictors of cardiovascular events. The value of these inflammatory markers as independent predictors remains controversial. METHODS: We examined plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein as markers of risk for coronary heart disease among women participating in the Nurses' Health Study and men participating in the Health Professionals Follow-up Study in nested case-control analyses. Among participants who provided a blood sample and who were free of cardiovascular disease at baseline, 239 women and 265 men had a nonfatal myocardial infarction or fatal coronary heart disease during eight years and six years of follow-up, respectively. Using risk-set sampling, we selected controls in a 2:1 ratio with matching for age, smoking status, and date of blood sampling. RESULTS: After adjustment for matching factors, high levels of interleukin-6 and C-reactive protein were significantly related to an increased risk of coronary heart disease in both sexes, whereas high levels of soluble TNF-alpha receptors were significant only among women. Further adjustment for lipid and nonlipid factors attenuated all associations; only C-reactive protein levels remained significant. The relative risk among all participants was 1.79 for those with C-reactive protein levels of at least 3.0 mg per liter, as compared with those with levels of less than 1.0 mg per liter (95 percent confidence interval, 1.27 to 2.51; P for trend <0.001). Additional adjustment for the presence or absence of diabetes and hypertension moderately attenuated the relative risk to 1.68 (95 percent confidence interval, 1.18 to 2.38; P for trend = 0.008). CONCLUSIONS: Elevated levels of inflammatory markers, particularly C-reactive protein, indicate an increased risk of coronary heart disease. Although plasma lipid levels were more strongly associated with an increased risk than were inflammatory markers, the level of C-reactive protein remained a significant contributor to the prediction of coronary heart disease.

Adult↗

A randomized controlled open trial of population-based disease and case management in a Medicare Plus Choice health maintenance organization.

INTRODUCTION: The object of this study was to examine the effect of population-based disease management and case management on resource use, self-reported health status, and member satisfaction with and retention in a Medicare Plus Choice health maintenance organization (HMO). METHODS: Study design consisted of a prospective, randomized controlled open trial of 18 months' duration. Participants were 8504 Medicare beneficiaries aged 65 and older who had been continuously enrolled for at least 12 months in a network model Medicare Plus Choice HMO serving a contiguous nine-county metropolitan area. Members were care managed with an expert clinical information system and frequent telephone contact. Main outcomes included self-reported health status measured by the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), resource use measured by admission rates and bed-days per thousand per year, member satisfaction, and costs measured by paid claims. RESULTS: More favorable outcomes occurred in the intervention group for satisfaction with the health plan (P < .01) and the social function domain as measured by SF-36 (P = .04). There was no difference in member retention or mortality between groups. Use of skilled nursing home services was significantly lower in the intervention group than in the control (616 vs 747 days per thousand members per year, P = .02). This reduction, however, did not lead to lower mean total expenditures in the intervention group compared with the control (6828 dollars per member for 18 months vs 7001 dollars, P = .61). CONCLUSION: Population-based disease management and case management led to improved self-reported satisfaction and social function but not to a global net decrease in resource use or improved member retention.

Aged↗

Cardiovascular risk factors in women with and without rheumatoid arthritis.

OBJECTIVE: The risk of cardiovascular disease (CVD) is increased in patients with rheumatoid arthritis (RA). The objective of this study was to examine the distribution of known CVD risk factors and biomarkers of CVD in women with and without RA. METHODS: This study included two components: an examination of clinical CVD risk factors among women participating in the Nurses' Health Study, a prospective longitudinal cohort, and an analysis of CVD biomarkers among a subgroup of women from this cohort who provided a blood specimen in 1989 (biospecimen cohort). Data regarding clinical risk factors for CVD were collected in 1990 by mailed questionnaire. The diagnosis of RA was confirmed through a structured medical record abstraction. We compared clinical risk factors for CVD and biomarkers of CVD between women with and without RA, adjusting for age, body mass index (BMI), smoking status, and menopause status. RESULTS: Women with RA (n = 287) were significantly more likely than women without RA (n = 87,019) to report no alcohol use (48.2% versus 39.4%) and past cigarette smoking (47.8% versus 38.0%). No significant differences between these groups were observed for current smoker status, BMI, regular aspirin use, diabetes, hypertension, physical activity, and family history of early myocardial infarction. In the biospecimen cohort (69 RA cases and 491 controls), the levels of several inflammatory biomarkers linked to CVD were significantly elevated in women with RA, including CRP, fibrinogen, sICAM-1, sTNFRI, sTNFRII, and osteoprotegerin. Levels of total cholesterol, low-density lipoprotein, triglycerides, apolipoprotein B, and Lp(a) were similar between groups. Levels of homocysteine were similar, but vitamin B(12) was significantly higher among women with RA than among the controls. CONCLUSION: In women participating in the Nurses' Health Study, most traditional CVD risk factors were similar between those who had RA and those who did not. However, as expected, biomarkers of inflammation associated with CVD were generally elevated in women with RA.

Adult↗

Accuracy of Medicare claims-based diagnosis of acute myocardial infarction: estimating positive predictive value on the basis of review of hospital records.

BACKGROUND: Many cardiovascular epidemiologic studies rely on diagnosis codes in health care claims databases. Despite important changes in the care and diagnosis of acute myocardial infarction (AMI), the validity of hospital discharge diagnosis codes for AMI in the US Medicare system has not been recently examined. Our objective was to examine the accuracy of International Classification of Diseases--ninth revision--Clinical Modifications (ICD-9-CM) discharge diagnosis codes and diagnosis-related groups (DRG) codes for AMI in a Medicare claims database. METHODS: We sampled hospitalization episodes from Medicare beneficiaries in Pennsylvania during 1999, 2000, or both. We used Medicare data to identify patients with hospitalizations containing indicators of AMI (ICD-9-CM diagnosis codes 410.X0 and 410.X1 or DRG codes 121, 122, and 123). Hospital records for these episodes were reviewed by trained abstractors using World Health Organization criteria for diagnosing AMI. We then calculated the positive predictive value of Medicare claims-based definitions of AMI. RESULTS: Of 2200 hospitalization episodes with Medicare diagnosis codes suggestive of AMI, 2022 hospital records (91.9%) were obtained. The positive predictive value for a primary Medicare claims-based definition was 94.1% (95% CI, 93.0%-95.2%). Positive predictive values for alternative claims-based definitions ranged slightly, with the definition including DRG codes and length-of-stay restrictions yielding the highest positive predictive value, 95.4% (95% CI, 94.3%-96.4%). Subjects with a history of myocardial infarction had a significantly lower positive predictive value than subjects without a history of myocardial infarction (88.1% vs 94.6%, P <.001). CONCLUSIONS: In this study, we observed high positive predictive values for a Medicare claims-based diagnosis of AMI and a diagnosis based on structured hospital record review.

Aged↗

Employment status, social ties, and caregivers' mental health.

The purpose of this study of mid-life and older women was to assess the relation between informal care provision and depressive symptoms, taking into account concurrent demands on women's time (including multiple caregiving roles and employment outside the home) as well as participants' access to potentially supportive social ties. This cross-sectional study included women ages 46-71, free from major disease, who provided complete health and social information in the 1992 Nurses' Health Study follow-up survey (n = 61,383). In logistic regression models predicting depressive symptoms, we examined the interaction between employment outside the home and informal care provision for a disabled or ill spouse or parent. We also investigated level of social ties, measured with the Berkman-Syme Social Network Index, as a potential modifier of the association between informal care provision and depressive symptoms. In all analyses, higher weekly time commitment to informal care for a spouse or parent was associated with increased risk of depressive symptoms. This relationship persisted whether women were not employed outside the home, were employed full-time, or were employed part-time. Higher weekly time commitment to informal care provision was associated with increased risk of depressive symptoms whether women were socially integrated or socially isolated. However, both informal care provision and social ties were potent independent correlates of depressive symptoms. Therefore, women who reported high spousal care time commitment and few social ties experienced a dramatic elevation in depressive symptoms, compared to women with no spousal care responsibilities and many social ties (OR for depressive symptoms=11.8; 95% CI 4.8, 28.9). We observed the same pattern among socially isolated women who cared for their parent(s) many hours per week, but the association was not as strong (OR for depressive symptoms=6.5; 95% CI 3.4, 12.7). In this cross-sectional study, employment status did not seem to confer additional mental health risk or benefit to informal caregivers, while access to extensive social ties was associated with more favorable caregiver health outcomes.

Adult↗

Kidney dysfunction, inflammation, and coronary events: a prospective study.

Kidney dysfunction and high C-reactive protein (CRP) levels are independently associated with coronary events. However, it is unclear whether the risk of coronary events associated with decreased kidney function is at least partially mediated by inflammation and whether the association between inflammatory biomarkers and coronary events is influenced by level of kidney function. With the use of a prospective, nested, case-control study design, the association among kidney function, inflammatory biomarker levels, and coronary events was studied. A total of 244 women who were participants in the Nurses' Health Study and had no history of cardiovascular disease received a diagnosis of an incident coronary event (defined as nonfatal myocardial infarction or death as a result of coronary disease) during the follow-up period from 1990 to 1998 and were matched to 486 control subjects. Serum creatinine and inflammatory biomarker levels were measured in blood samples collected in 1989. Creatinine clearance (CrCl) was estimated using creatinine, age, weight, and height. In multivariate analyses, the odds ratio (OR) for a coronary event in women with an estimated CrCl <60 ml/min was 2.33 (95% confidence interval [CI], 1.01 to 5.38) compared with those with a CrCl > or =90 ml/min. When soluble tumor necrosis factor receptor (sTNFR) I and II levels were added into this model individually, the observed OR for women with CrCl <60 ml/min was attenuated. In analyses stratified by estimated CrCl, higher high-sensitivity CRP (hs-CRP), IL-6, and sTNFR I and II levels each were significantly associated with an increased odds of coronary events in women with an estimated CrCl < or =74 ml/min but not in women with an estimated CrCl > or =75 ml/min. The OR per 5-mg/L unit increase in hs-CRP was 1.68 (95% CI, 1.13 to 2.52) for women with an estimated CrCl < or =74 ml/min, compared with 1.23 (95% CI, 0.86 to 1.76) and 0.99 (95% CI, 0.76 to 1.29) for women with an estimated CrCl 75 to 89 and > or =90 ml/min, respectively (P = 0.004 for interaction). In conclusion, kidney dysfunction is associated with an increased odds of coronary events, and inflammation, as assessed by higher sTNFR I and II levels, may mediate some of this risk. Higher inflammatory biomarkers levels, specifically, hs-CRP, IL-6, and sTNFR I and II, were significantly associated with coronary events only in women with reduced kidney function. These findings warrant further investigation in other populations.

Adult↗

Cardiovascular morbidity and mortality in women diagnosed with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis may be associated with an increased risk of cardiovascular disease. We compared the incidence rates of myocardial infarction and stroke in subjects with and without rheumatoid arthritis. METHODS AND RESULTS: A prospective cohort study was conducted among the 114 342 women participating in the Nurses' Health Study who were free of cardiovascular disease and rheumatoid arthritis at baseline in 1976. All self-reported cases of rheumatoid arthritis were confirmed by medical record review. Fatal and nonfatal myocardial infarctions and strokes were similarly confirmed. Multivariate pooled logistic regression was used to adjust for potential cardiovascular risk factors. Five hundred twenty-seven incident cases of rheumatoid arthritis and 3622 myocardial infarctions and strokes were confirmed during 2.4 million person-years of follow-up. The adjusted relative risk of myocardial infarction in women with rheumatoid arthritis compared with those without was 2.0 (95% confidence interval [CI], 1.23 to 3.29). For stroke, the adjusted relative risk was 1.48 (95% CI, 0.70 to 3.12). Women who had rheumatoid arthritis for at least 10 years had a risk for myocardial infarction of 3.10 (95% CI, 1.64 to 5.87). CONCLUSION: In this large prospective cohort of women, participants with rheumatoid arthritis had a significantly increased risk of myocardial infarction but not stroke compared with those without rheumatoid arthritis. If these data are confirmed, aggressive coronary heart disease prevention strategies should be tested for persons with rheumatoid arthritis.

Adult↗

Reverberations of family illness: a longitudinal assessment of informal caregiving and mental health status in the Nurses' Health Study.

OBJECTIVES: . This study examined the association between caregiving for disabled or ill family members, estimated to occur in more than 22 million US households, and change in mental health. METHODS: We assessed 4-year change in mental health among 37 742 Nurses' Health Study participants with the Medical Outcomes Study Short-Form 36. RESULTS: Women who provided 36 or more weekly hours of care to a disabled spouse were almost 6 times more likely than noncaregivers to experience depressive or anxious symptoms (multivariate odds ratio [OR] = 5.6; 95% confidence interval [CI] = 3.8, 8.3). Caring for a disabled or ill parent (>or= 36 weekly hours) was associated with a less dramatic elevation in depressive or anxious symptoms (multivariate OR = 2.0; 95% CI = 0.9, 4.3). CONCLUSIONS: In this population, caregiving was associated with increased risk of depressive or anxious symptoms.

Adult↗