Treatment with TNF blockers and mortality risk in patients with rheumatoid arthritis

OBJECTIVE: To assess mortality in patients with rheumatoid arthritis (RA) treated with tumour necrosis factor (TNF) inhibitors, compared with a standard RA population. METHODS: Patients were recruited from a regional register, which includes over 90% of patients with RA treated with TNF blockers in the area in 1999 or later, and a local community-based cohort of patients with RA, established in 1997. Of a total of 1430 patients in the combined cohort <80 years old, 921 received treatment with TNF inhibitors during the study period. The total cohort was linked with the national register for cause of death. Overall mortality in those treated versus those not treated with TNF blockers was estimated using standardised mortality ratios and time-dependent Cox proportional hazards. RESULTS: There were 188 deaths per 7077 person-years at risk in the total cohort. Controlling for age, sex, disability and baseline comorbidity, the adjusted HR for death was 0.65 (95% CI 0.46 to 0.93) in those treated with anti-TNF versus those not treated. The effect was significant in women (HR = 0.52, 95% CI 0.33 to 0.82) but not in men (HR = 0.95, 95% CI 0.52 to 1.71). CONCLUSION: After adjusting for disease severity, treatment with TNF inhibitors was found to be associated with a reduced mortality in women but not men with RA. These findings are compatible with a critical role for inflammation in RA-associated premature mortality.     

Prediction of mortality in rheumatoid arthritis based on disease activity markers

OBJECTIVE: The risks and predictors for mortality in patients with rheumatoid arthritis (RA) were examined in a cohort of 152 consecutive outpatients (119 women, 33 men) seen in a 2 month period. METHODS: We evaluated 4 measures of disease activity: erythrocyte sedimentation rate (ESR), physician and patient global assessment of disease activity, and the Ritchie Articular Index (RAI) as mortality predictors, adjusting for disease severity, treatment, and cardiovascular disease (CVD) comorbidity. RESULTS: During followup from 1978 through 1998, 111 patients (86 women, 25 men) died, and only one was lost to followup. The standardized mortality ratio for women was 161 (95% confidence interval 129-199), for men 152 (95% CI 99-223), and for both sexes combined 156 (95% CI 128-188). In a proportional hazards model adjusted for age and sex, at the beginning of the period and for the whole group, significant predictors of mortality were Steinbrocker functional class, Larsen index, CVD comorbidity, use of corticosteroids ever, ESR, and the physician and patient global assessment of disease activity; but the rheumatoid factor (RF), RAI, and use of disease modifying antirheumatic drugs were not significant predictors. When evaluating the 4 assessments of disease activity adjusting for confounders, only physician global assessment hazard ratio (HR) = 1.32 per 1 SD (95% CI 1.00-1.74) and ESR HR = 1.47 per 1 SD (95% CI 1.11-1.93) were significant predictors. CONCLUSION: This longterm followup study of a single clinical patient cohort showed a significant increase in mortality among patients with RA compared to the general population in Malm?. In addition to disease damage and CVD comorbidity, measures of disease activity independently predicted mortality, which supports the hypothesis that improving these variables may also improve longterm outcome.     

Association of mortality with disease severity in rheumatoid arthritis, independent of comorbidity

OBJECTIVE: To measure the extent to which mortality in rheumatoid arthritis (RA) is associated with disease severity, independent of the presence of coexistent diseases (comorbidity). METHODS: We measured disease severity and comorbidity among RA patients attending scheduled appointments at a rheumatology clinic. We used the Duke Severity of Illness Checklist (DUSOI), a clinical judgment-based measure of the severity of disease. We disaggregated the DUSOI into an RA component (RADUSOI), which we used to measure RA disease severity, together with a physician-rated 10-point global RA severity assessment. We measured comorbidity using the non-RA component of the DUSOI (COMDUSOI) and using the Charlson Comorbidity Index. Patients were contacted periodically for up to 6 years, during which we recorded deaths. We estimated the effect of disease severity and comorbidity on mortality using Kaplan-Meier survival curves, Cox proportional hazards models, and logistic regression with receiver operating characteristics (ROC) curve analysis. RESULTS: The sample comprised 779 patients. Followup ranged from 0.1 year to 6.3 years (mean 2.52 years), for an observation period of 2,315 patient-years. Seventy-five patients died (9.6%), for a total mortality of 3.2 per 100 patient-years (95% confidence interval 2.6-4.1). Both disease severity and comorbidity displayed significant bivariate associations with mortality. In multivariate Cox models adjusted for age, sex, and disease duration, the RADUSOI and global RA severity scores were associated with mortality independent of either the COMDUSOI or Charlson Comorbidity scores. The area under the ROC curve for a logistic model on mortality increased from 0.79 with age, sex, and disease duration included, to 0.84 after adding RA severity and comorbidity (P < or = 0.005 for the increase in ROC area). CONCLUSION: RA disease severity is significantly associated with mortality regardless of the presence of comorbid disease. Combined with each patient's age, sex, and disease duration, information on RA severity and comorbidity allows an accurate prediction of mortality among patients with RA.     

首都钢铁公司男工主要死亡原因的前瞻性研究

目的 探讨首都钢铁公司男工队列人群的主要死亡原因及其影响因素。方法 2001年对1974、1979和1980年入选的5137名平均年龄在45岁的北京首都钢铁公司男工进行了全死因及冠心病、脑卒中发病死亡的随访,平均随访时间为2008年。疾病死亡登记按MONICA方案进行。用观察人年计算死亡率,并采用我国2000年人口构成进行年龄调整。用Cox回归模型进行多因素分析,用校正的相对危险度计算人群归因危险度百分比。结果 随访期间共发生死亡事件760例,全因死亡率为732．9／10万人年,年龄标化死亡率为643．0／10万人年。排序在前3位的死亡原因分别是恶性肿瘤、脑卒中和心脏疾病,其年龄标化死亡率分别为231．3／10万人年、139．3／10万人年和96．4／10万人年。因恶性肿瘤、脑卒中和心脏病死亡的人数占总死亡人数的77．4％。在恶性肿瘤死亡中肺癌的死亡居第一位,在心血管疾病死亡中排在前列的死因分别是脑卒中、冠心病、肺心病和心衰。经多因素调整后,吸烟、高血压和高胆固醇血症总死亡的相对危险度分别是1．440（1．174～1．765）、1．615（1．370～1．904）和1．274（1．057～1．537）,人群归因危险度百分比分别是24．4％、16．5％和4．5％。结论 癌症和心脑血管病是首都钢铁公司男工的主要死因,吸烟、高血压和高胆固醇血症是增加总死亡率的主要原因。     

High incidence of cardiovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors.

OBJECTIVE: To compare the incidence of cardiovascular (CV) events in persons with rheumatoid arthritis (RA) with that in people from the general population, adjusting for traditional CV risk factors. METHODS: Two hundred thirty-six consecutive patients with RA were assessed for the 1-year occurrence of 1) CV-related hospitalizations, including myocardial infarction, stroke or other arterial occlusive events, or arterial revascularization procedures, or 2) CV deaths. Both outcomes were ascertained by medical records or death certificates. For comparison, we used CV events that occurred during an 8-year period among participants in an epidemiologic study of atherosclerosis and CV disease who were ages 25-65 years at study entry. We calculated the age- and sex-stratified incidence rate ratio (IRR) of CV events between the 2 cohorts and used Poisson regression to adjust for age, sex, smoking status, diabetes mellitus, hypercholesterolemia, systolic blood pressure, and body mass index. RESULTS: Of the 236 RA patients, 234 were observed for 252 patient-years, during which 15 CV events occurred. Of these, 7 incident events occurred during the 204 patient-years contributed by patients ages 25-65 years, for an incidence of 3.43 per 100 patient-years. In the comparison cohort, 4,635 community-dwelling persons were followed up for 33,881 person-years, during which 200 new events occurred, for an incidence of 0.59 per 100 person-years. The age- and sex-adjusted IRR of incident CV events associated with RA was 3.96 (95% confidence interval [95% CI] 1.86-8.43). After adjusting for CV risk factors using Poisson regression, the IRR decreased slightly, to 3.17 (95% CI 1.33-6.36). CONCLUSION: The increased incidence of CV events in RA patients is independent of traditional CV risk factors. This suggests that additional mechanisms are responsible for CV disease in RA. Physicians who provide care to individuals with RA should be aware of their increased risk of CV events and implement appropriate diagnostic and therapeutic measures.     

The effect of obesity on disability vs mortality in older Americans

BACKGROUND: The association between obesity and mortality is reduced or eliminated in older subjects. In addition to mortality, disability is an important health outcome. The objectives of this study were to examine the association between body mass index (BMI), calculated as weight in kilograms divided by height in meters squared, and subsequent disability and mortality among older Americans, as well as to estimate the effect of BMI on life expectancy and disability-free life expectancy among older Americans. METHODS: We studied 8359 non-Hispanic white Americans, 1931 African Americans, and 2435 Mexican Americans 65 years or older who were not disabled at baseline from 5 sites of the Established Populations for Epidemiologic Studies of the Elderly. Measures included BMI, medical conditions, activities of daily living, and demographic information. Cox proportional hazards regression analysis was used to estimate the hazard ratios (HRs) for subsequent disability and mortality during 7 years of follow-up. Total life expectancy and disability-free life expectancy were estimated using the interpolation of Markov chain approach. RESULTS: The lowest HR (1.02; 95% confidence interval [CI], 0.94-1.10) for disability was at a BMI of 25 to less than 30. Subjects with BMIs of lower than 18.5 or 30 or higher at baseline were significantly more likely to experience disability during the follow-up period. In contrast, the lowest HRs for mortality were seen among subjects with BMIs of 25 to less than 30 (HR, 0.78; 95% CI, 0.72-0.85) and 30 to less than 35 (HR, 0.80; 95% CI, 0.72-0.90), with subjects with BMIs of lower than 25 or 35 or higher experiencing higher hazards for mortality. Disability-free life expectancy is greatest among subjects with a BMI of 25 to less than 30. CONCLUSION: Assessments of the effect of obesity on the health of older Americans should account for mortality and incidence of disability.     

Associations between body mass index and all-cause mortality: A systematic review and meta-analysis

Fasting insulin and c-reactive protein confound the association between mortality and body mass index. An increase in fat mass may mediate the associations between hyperinsulinemia, hyperinflammation, and mortality. The objective of this study was to describe the “average” associations between body mass index and the risk of mortality and to explore how adjusting for fasting insulin and markers of inflammation might modify the association of BMI with mortality. MEDLINE and EMBASE were searched for studies published in 2020. Studies with adult participants where BMI and vital status was assessed were included. BMI was required to be categorized into groups or parametrized as non-first order polynomials or splines. All-cause mortality was regressed against mean BMI squared within seven broad clinical populations. Study was modeled as a random intercept. β coefficients and 95% confidence intervals are reported along with estimates of mortality risk by BMIs of 20, 30, and 40 kg/m². Bubble plots with regression lines are drawn, showing the associations between mortality and BMI. Splines results were summarized. There were 154 included studies with 6,685,979 participants. Only five (3.2%) studies adjusted for a marker of inflammation, and no studies adjusted for fasting insulin. There were significant associations between higher BMIs and lower mortality risk in cardiovascular (unadjusted β −0.829 [95% CI −1.313, −0.345] and adjusted β −0.746 [95% CI −1.471, −0.021]), Covid-19 (unadjusted β −0.333 [95% CI −0.650, −0.015]), critically ill (adjusted β −0.550 [95% CI −1.091, −0.010]), and surgical (unadjusted β −0.415 [95% CI −0.824, −0.006]) populations. The associations for general, cancer, and non-communicable disease populations were not significant. Heterogeneity was very large (I² ≥ 97%). The role of obesity as a driver of excess mortality should be critically re-examined, in parallel with increased efforts to determine the harms of hyperinsulinemia and chronic inflammation.     

Prognostic importance of low body mass index in relation to cardiovascular mortality in rheumatoid arthritis

OBJECTIVE: Various etiologic mechanisms have been implicated in the observed increase in cardiovascular mortality in rheumatoid arthritis (RA). Body mass index (BMI) is associated with cardiovascular mortality in the general population. This study compared the effect of BMI on cardiovascular mortality in a population-based cohort of subjects with RA with that in a cohort of individuals without RA from the same population. METHODS: The RA cohort comprised all members of an incidence cohort of Rochester, Minnesota residents ages > or =18 years who were first diagnosed with RA (by the American College of Rheumatology 1987 criteria) from 1955 through 1994. An age- and sex-matched comparison cohort of subjects without RA was assembled. Both cohorts were followed up longitudinally through their complete (inpatient, outpatient) medical records beginning at age 18 years and continuing until death, migration, or January 1, 2001, and the details of weight and height changes during this period were recorded. High BMI was defined as a BMI >30 kg/m(2) and low BMI as <20 kg/m(2). Cox regression models were used to estimate the effect of BMI on cardiovascular mortality after accounting for traditional cardiac risk factors and malignancies. RESULTS: RA subjects with low BMI at incidence had a significantly higher risk of cardiovascular death (hazard ratio [HR] 3.34, 95% confidence interval [95% CI] 2.23-4.99) compared with non-RA subjects with normal BMI, after adjusting for age, sex, personal cardiac history, smoking status, and presence of diabetes, hypertension, and malignancies. RA subjects with normal BMI at incidence who experienced low BMI during followup also had a higher risk of cardiovascular death (HR 2.09, 95% CI 1.50-2.92) when compared with non-RA subjects who maintained normal BMI throughout followup. CONCLUSION: Among patients with RA, low BMI is associated with a significantly increased risk of cardiovascular death.     

Body Mass Index,Weight Loss,and Cause‐Specific Mortality in Rheumatoid Arthritis

Objective

To examine associations of body mass index (BMI) and weight loss with cause‐specific mortality in rheumatoid arthritis (RA).

Methods

A cohort of US veterans with RA was followed until death or through 2013. BMI was categorized as underweight, normal, overweight, and obese. Weight loss was calculated as the 1) annualized rate of change over the preceding 13 months, and 2) cumulative percent. Vital status and cause of death were obtained from the National Death Index. Multivariable competing‐risks regression models were utilized to assess the time‐varying associations of BMI and weight loss with cause‐specific mortality.

Results

Among 1,600 participants and 5,789 patient‐years of followup, 303 deaths occurred (95 cardiovascular, 74 cancer, and 46 respiratory). The highest weight‐loss rate and weight‐loss percent were associated with a higher risk of cardiovascular mortality (rate: subdistribution hazard ratio [sHR] 2.27 [95% confidence interval (95% CI) 1.61–3.19]; percent: sHR 2.31 [95% CI 1.06–5.01]) and cancer mortality (rate: sHR 2.36 [95% CI 1.11–5.01]; percent: sHR 1.90 [95% CI 1.00–3.62]). Overweight BMI was protective of cardiovascular mortality (sHR 0.59 [95% CI 0.38–0.91]), while underweight BMI was associated with a near 3‐fold increased risk of respiratory mortality (sHR 2.93 [95% CI 1.28–6.67]). Incorporation of time‐varying BMI and weight loss in the same models did not substantially alter individual associations for cardiovascular and cancer mortality, but an association between weight‐loss percentage and respiratory mortality was attenuated after BMI adjustment.

Conclusion

Both BMI and weight loss are predictors of cause‐specific mortality in RA. Weight loss is a strong predictor of cardiovascular and cancer mortality, while underweight BMI is a stronger predictor of respiratory mortality.     

Antecedent blood pressure, body mass index, and the risk of incident heart failure in later life

Higher blood pressure and body mass index (BMI) are risk factors for heart failure. It is unknown whether the presence of these risk factors in midadulthood affect the future development of heart failure. In the community-based Framingham Heart Study, we examined the associations of antecedent blood pressure and BMI with heart failure incidence in later life. We studied 3362 participants (57% women; mean age: 62 years) who attended routine examinations between 1969 and 1994 and examined their systolic and diastolic blood pressure, pulse pressure, and BMI at current (baseline), recent (average of readings obtained 1 to 10 years before baseline), and remote (average of readings obtained 11 to 20 years before baseline) time periods. During 67 240 person-years of follow-up, 518 participants (280 women) developed heart failure. Current, recent, and remote systolic pressure; pulse pressure; and BMI were individually associated with incident heart failure (all P<0.001). Recent systolic pressure (hazards ratio [HR] per 1-SD increment: 1.31; 95% CI: 1.11 to 1.55), pulse pressure (HR per 1-SD increment: 1.33; 95% CI: 1.14 to 1.54), and BMI (HR per unit increase: 1.15; 95% CI: 1.08 to 1.23) were associated with heart failure risk even after adjusting for current measures. Similarly, remote systolic pressure (HR per 1 SD: 1.17; 95% CI: 1.04 to 1.31), pulse pressure (HR per 1 SD: 1.17; 95% CI: 1.06 to 1.31), and BMI (HR per unit: 1.09; 95% CI: 1.05 to 1.14) remained associated with incident heart failure after adjusting for current measurements. Higher blood pressure and BMI in midlife are harbingers of increased risk of heart failure in later life. Early risk factor modification may decrease heart failure burden.     

Rising incidence and persistently high mortality of hospitalized pneumonia: a 10-year population-based study in Denmark

BACKGROUND: Little is known about temporal trends in the incidence and mortality of pneumonia in the general population. METHODS: We conducted a population-based cohort study in three Danish counties (population 1.4 million) to examine changes in the incidence and 30- and 90-day mortality associated with hospitalized pneumonia between 1994 and 2004. All adults hospitalized with a first-time diagnosis of pneumonia (n = 41 793) were identified in hospital discharge registries and followed for mortality through the Danish Civil Registry System. We determined age-standardized incidence rates and adjusted mortality rates associated with calendar year, gender, age and comorbidity. RESULTS: Between 1994 and 2003, the incidence of hospitalized pneumonia amongst adults increased from 288 per 100 000 person-years to 442 per 100 000 person-years, equivalent to an age-standardized incidence rate ratio of 1.50. The cumulative mortality within 30 and 90 days of admission was 15.2% and 21.9%, respectively, ranging from a 90-day mortality of 2.5% in patients aged 15-39 years to 34.7% in those aged 80 and over. Advanced age was the most important poor prognostic factor, followed by a high comorbidity score and male gender. The adjusted mortality rate ratios amongst patients with hospitalized pneumonia in 1999-2004, when compared with 1994-1998, were 0.89 (95% CI 0.85-0.94) after 30 days and 0.91 (95% CI 0.88-0.95) after 90 days. CONCLUSIONS: The incidence of hospitalized pneumonia in Denmark has increased considerably during the last 10 years and, combined with persistently high mortality rates, is of clinical and public health concern.     

Comparison of characteristics and outcomes of asymptomatic versus symptomatic left ventricular dysfunction in subjects 65 years old or older (from the Cardiovascular Health Study)

Although asymptomatic left ventricular (LV) systolic dysfunction (ALVSD) is common, its phenotype and prognosis for incident heart failure (HF) and mortality are insufficiently understood. Echocardiography was done in 5,649 participants in the Cardiovascular Health Study (age 73.0 ± 5.6 years, 57.6% women). The clinical characteristics and cardiovascular risk factors of the participants with ALVSD were compared to those with normal LV function (ejection fraction ≥55%) and with symptomatic LV systolic dysfunction (SLVSD; ejection fraction <55% and a history of HF). Cox proportional hazards models were used to estimate the risk of incident HF and mortality in those with ALVSD. Also, comparisons were made among the LV ejection fraction subgroups using previously validated cutoff values (<45% and 45% to 55%), adjusting for the demographic and cardiovascular disease risk factors. Those with ALVSD (7.3%) were more likely to have cardiovascular risk factors than those in the reference group (without LV dysfunction or symptomatic HF) but less likely than those with SLVSD. The HF rate was 24 occurrences per 1,000 person-years in the reference group and 57 occurrences per 1,000 person-years in those with ALVSD. The HF rate was 45 occurrences per 1,000 person-years for those with ALVSD and mildly impaired LV dysfunction and 93 occurrences per 1,000 person-years for those with ALVSD and moderate to severe LV dysfunction. The mortality rate was 51 deaths per 1,000 person-years in the reference group, 90 deaths per 1,000 person-years in the ALVSD group, and 156 deaths per 1,000 person-years in the SLVSD group. Adjusting for covariates, compared to the reference group, ALVSD was associated with an increased risk of incident HF (hazard ratio 1.60, 95% confidence interval 1.35 to 1.91), cardiovascular mortality (hazard ratio 2.13, 95% confidence interval 1.81 to 2.51), and all-cause mortality (hazard ratio 1.46, 95% confidence interval 1.29 to 1.64). In conclusion, subjects with ALVSD are characterized by a greater prevalence of cardiovascular risk factors and co-morbidities than those with normal LV function and without HF. However, the prevalence is lower than in those with SLVSD. Patients with ALVSD are at an increased risk of HF and mortality, particularly those with greater severity of LV impairment.     

The risk of congestive heart failure in rheumatoid arthritis: a population-based study over 46 years

OBJECTIVE: It is hypothesized that the systemic inflammation associated with rheumatoid arthritis (RA) promotes an increased risk of cardiovascular (CV) morbidity and mortality. We examined the risk and determinants of congestive heart failure (CHF) in patients with RA. METHODS: We assembled a population-based, retrospective incidence cohort from among all individuals living in Rochester, Minnesota, in whom RA (defined according to the American College of Rheumatology 1987 criteria) was first diagnosed between 1955 and 1995, and an age- and sex-matched non-RA cohort. After excluding patients in whom CHF occurred before the RA index date, all subjects were followed up until either death, incident CHF (defined according to the Framingham Heart Study criteria), migration from the county, or until January 1, 2001. Detailed information from the complete medical records (including all inpatient and outpatient care provided by all local providers) regarding RA, ischemic heart disease, and traditional CV risk factors was collected. Cox models were used to estimate the effect of RA on the development of CHF, adjusting for CV risk factors and/or ischemic heart disease. RESULTS: The study population included 575 patients with RA and 583 subjects without RA. The CHF incidence rates were 1.99 and 1.16 cases per 100 person-years in patients with RA and in non-RA subjects, respectively (rate ratio 1.7, 95% confidence interval [95% CI] 1.3-2.1). After 30 years of followup, the cumulative incidence of CHF was 34.0% in patients with RA and 25.2% in non-RA subjects (P< 0.001). RA conferred a significant excess risk of CHF (hazard ratio [HR] 1.87, 95% CI 1.47-2.39) after adjusting for demographics, ischemic heart disease, and CV risk factors. The risk was higher among patients with RA who were rheumatoid factor (RF) positive (HR 2.59, 95% CI 1.95-3.43) than among those who were RF negative (HR 1.28, 95% CI 0.93-1.78). CONCLUSION: Compared with persons without RA, patients with RA have twice the risk of developing CHF. This excess risk is not explained by traditional CV risk factors and/or clinical ischemic heart disease.     

Survival of chronic hypercapnic COPD patients is predicted by smoking habits, comorbidity, and hypoxemia

STUDY OBJECTIVES: Chronic hypercapnia in patients with COPD has been associated with a poor prognosis. We hypothesized that, within this group of chronic hypercapnic COPD patients, factors that could mediate this hypercapnia, such as decreased maximum inspiratory mouth pressure (P(I(max))), decreased maximum expiratory mouth pressure (P(E(max))), and low hypercapnic ventilatory response (HCVR), could be related to survival. Other parameters, such as arterial blood gas values, airway obstruction (FEV1), body mass index (BMI), current smoking status, and the presence of comorbidity were studied as well. METHODS: A cohort of 47 chronic hypercapnic COPD patients recruited for short-term trials (1 to 3 weeks) in our institute was followed up for 3.8 years on average. Survival was analyzed using a Cox proportional hazards model. The risk factors considered were analyzed, optimally adjusted for age and gender. RESULTS: At the time of analysis 18 patients (10 male) were deceased. After adjusting for age and gender, P(I(max)), P(E(max)), and HCVR were not correlated with survival within this hypercapnic group. Current smoking (hazard ratio [HR], 7.0; 95% confidence interval [CI], 1.4 to 35.3) and the presence of comorbidity (HR, 5.5; 95% CI, 1.7 to 18.7) were associated with increased mortality. A higher Pa(O2) affected survival positively (HR, 0.6 per 5 mm Hg; 95% CI, 0.4 to 1.0). Pa(CO2) tended to be lower in survivors, but this did not reach statistical significance (HR, 2.0 per 5 mm Hg; 95% CI, 0.9 to 4.3). FEV1 and BMI were not significantly related with survival in hypercapnic COPD patients. CONCLUSION: In patients with chronic hypercapnia, only smoking status, the presence of comorbidity, and Pa(O2) level are significantly associated with survival. Airway obstruction, age, and BMI are known to be predictors of survival in COPD patients in general. However, these parameters do not seem to significantly affect survival once chronic hypercapnia has developed.     

Relation of obesity to recurrence rate and burden of atrial fibrillation

Obesity is associated with new-onset atrial fibrillation (AF). However, the effect of obesity on AF recurrence or burden has not been studied. The aim of this study was to investigate the relation between AF recurrence, AF burden, and body mass index (BMI). A limited-access data set from the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial provided by the National Heart, Lung, and Blood Institute was used. Statistical analysis was done with a generalized linear mixed model. In 2,518 patients who had BMIs recorded, higher BMI was associated with a higher number of cardioversions (odds ratio [OR] 1.017, 95% confidence interval [CI] 1.005 to 1.029 for a BMI increase of 1 kg/m(2); OR 1.088, 95% CI 1.024 to 1.155 for a BMI increase of 5 kg/m(2); OR 1.183, 95% CI 1.049 to 1.334 for a BMI increase of 10 kg/m(2); p = 0.006 for each). Increased BMI was also associated with a higher likelihood of being in AF on follow-up (OR 1.020, 95% CI 1.002 to 1.038 per 1 kg/m(2) increased BMI, p = 0.0283; OR 1.104, 95% CI 1.011 to 1.205 per 5 kg/m(2) increased BMI, p = 0.0283; OR 1.218, 95% CI 1.021 to 1.452 per 10 kg/m(2) increased BMI, p = 0.0283). In a multivariate analysis, left atrial size but not BMI was an independent predictor of AF recurrence and AF burden. Because left atrial size was correlated with BMI, the effect of BMI on AF can be likely explained by greater left atrial size in subjects with higher BMIs. In conclusion, obesity is associated with a higher incidence of recurrence of AF and greater AF burden.     

Progression of HIV infection and mortality by hepatitis C infection in patients with haemophilia over 20 years.

Hepatitis C virus (HCV) infection is an important cause of mortality in human immune deficiency virus (HIV)-positive haemophiliacs. This study describes progression to AIDS, death from HCV end-stage liver disease (ESLD) and all-cause mortality over 20 years. All HIV-positive haemophiliacs in La Paz University Hospital were included in this cohort. HIV seroconversion was estimated using mathematical techniques for interval-censored data from 1979 to 1985. Poisson regression was used to estimate rates of AIDS, death from ESLD and all causes in different periods: before 1988, 1988-89, 1990-91, 1992-93, 1994-95, 1996-97 and 1998-2001 using competing risk models. Among 383 cohort members, global AIDS incidence was 9.7 per 100 person-years, peaking in 1992-93 and dropping by 87% in 1998-2001 compared with before 1988 [incidence rate ratio (IRR) 0.13; 95% CI: 0.03-0.53]. Overall mortality was 7.5 per 100 person-years, was highest from 1992 to 1997, and fell by 66% in 1998-2001 compared with before 1988 (IRR 0.34; 95% CI: 0.14-0.81). Eighteen (5%) persons died of ESLD which represented 19% of deaths before 1988, 4% during 1988-89, 1990-91 and 1992-93, 2% in 1994-95, 10% in 1996-97 and 33% in 1998-2001. Overall death rate from ESLD was 0.5 cases per 100 person-years with no statistically significant trend observed over time. Important reductions in HIV disease progression to AIDS and death have been observed from 1998 to 2001, and can be attributed to highly active antiretroviral therapy. Although no increase in the rate of HCV-related deaths can be demonstrated, HCV accounts for an increasing proportion of deaths in the recent years.     

Association between carotid atherosclerosis and markers of inflammation in rheumatoid arthritis patients and healthy subjects

OBJECTIVE: To examine the relationship between markers of systemic inflammation and carotid atherosclerosis in patients with rheumatoid arthritis (RA) and healthy controls. METHODS: Carotid artery intima-media thickness (IMT) and carotid plaque were measured using high-resolution B-mode ultrasound in 204 patients with RA, ages 40-85, and 102 age- and sex-matched healthy persons. No subject in either group had ever smoked cigarettes. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were used to measure systemic inflammation. The relationship of the carotid artery IMT and carotid plaque to inflammation markers was examined, adjusting for age, sex, RA versus control status, and the cardiovascular (CV) risk factors hypercholesterolemia, systolic blood pressure, diabetes mellitus, and body mass index (BMI). RESULTS: A significant linear trend for increased carotid artery IMT was associated with increasing ESR and CRP categories (r = 0.16, P = 0.004 for ESR, and r = 0.13, P = 0.02 for CRP). These trends did not differ among RA cases and controls, and were independent of age, sex, and CV risk factors. The difference in carotid artery IMT between the lowest and highest categories of ESR was 0.221 mm (95% confidence interval [95% CI] 0.767-1.020, P = 0.02). The difference between extreme CRP categories was 0.275 mm (95% CI 0.039-0.509, P = 0.02). Both remained significant after CV risk factor adjustment. Carotid plaque displayed a similar relationship to markers of inflammation. CONCLUSION: Increased carotid artery IMT and the presence of carotid plaque are associated with markers of systemic inflammation in patients with RA and in healthy subjects. This observation is consistent with hypotheses that assign a role to systemic inflammation in atherosclerosis, and may have implications regarding RA and other chronic inflammatory diseases.     

Use of nonbiologic disease-modifying antirheumatic drugs and risk of infection in patients with rheumatoid arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is associated with increased frequency of and mortality from infections, which may be related to host factors, RA itself, inflammation, or medication side effects. This study was undertaken to determine the effect of nonbiologic disease-modifying antirheumatic drugs (DMARDs) on infection risk in RA. METHODS: We performed a retrospective, longitudinal study of a population-based RA cohort in British Columbia, Canada, followed from January 1996 to March 2003 using administrative data. We evaluated mild infections (requiring a physician visit or antibiotics) and serious infections (requiring or complicating hospitalization). Adjusted risk of mild and serious infections associated with DMARD exposure was estimated using generalized estimating equation extension of multivariate Poisson regression models, after adjusting for baseline covariates (age, sex, RA duration, socioeconomic status) and time-dependent covariates (corticosteroids, comorbidity, prior infections). RESULTS: A total of 27,710 individuals with RA provided 162,710 person-years of followup. Of these, 25,608 (92%) had at least 1 mild infection and 4,941 (18%) had at least 1 serious infection. Use of DMARDs without corticosteroids was associated with a small decrease in mild infection risk of statistical significance but unclear clinical significance (adjusted rate ratio [RR] 0.90, 95% confidence interval [95% CI] 0.88-0.93 relative to no corticosteroid or DMARD use). Use of DMARDs without corticosteroids was not associated with increased serious infection risk (adjusted RR 0.92, 95% CI 0.85-1.0). Use of corticosteroids increased the risk of mild and serious infections. CONCLUSION: Our results indicate that use of nonbiologic DMARDs, including methotrexate, does not increase the risk of infection in RA, whereas use of corticosteroids does. This has important implications for counseling individuals with RA concerning risks and benefits of DMARDs.     

Rates and causes of death in Chiradzulu District, Malawi, 2008: a key informant study

In September 2008, we measured all-cause mortality in Chiradzulu District, Malawi (population 291, 000) over a 60-day retrospective period, using capture-recapture analysis of three lists of deaths provided by (i) key community informants, (ii) graveyard officials and (iii) health system sources. Estimated crude and under-5-year mortality rates were 18.6 (95% CI 13.9-24.5) and 30.6 (95% CI 17.5-59.9) deaths per 1000 person-years. We also classified causes of death through verbal autopsy interviews on 50 deaths over the previous 40 days. Half of deaths were attributable to infection, and half of deaths among children aged under 5 were attributable to neonatal causes. HIV/AIDS was the leading cause of death (16.6%), with a cause-attributable mortality rate of 1.8 (0.4-3.6) deaths per 1000 person-years.     

Cardiovascular, rheumatologic, and pharmacologic predictors of stroke in patients with rheumatoid arthritis: a nested, case-control study

OBJECTIVE: To determine the risk of stroke in patients with rheumatoid arthritis (RA) and risk factors associated with stroke. METHODS: We performed nested case-control analyses within a longitudinal databank, matching up to 20 controls for age, sex, and time of cohort entry to each patient with stroke. Conditional logistic regression was performed as an estimate of the relative risk of stroke in RA patients compared with those with noninflammatory rheumatic disorders, and to examine severity and anti-tumor necrosis factor (anti-TNF) treatment effects in RA. RESULTS: We identified 269 patients with first-ever all-category strokes and 67 with ischemic stroke, including 41 in RA patients. The odds ratio (OR) for the risk of all-category stroke in RA was 1.64 (95% confidence interval [95% CI] 1.16-2.30, P = 0.005), and for ischemic stroke was 2.66 (95% CI 1.24-5.70, P = 0.012). Ischemic stroke was predicted by hypertension, myocardial infarction, low-dose aspirin, comorbidity score, Health Assessment Questionnaire score, and presence of total joint replacement, but not by diabetes, smoking, exercise, or body mass index. Adjusted for cardiovascular and RA risk factors, ischemic stroke was associated with rofecoxib (P = 0.060, OR 2.27 [95% CI 0.97-5.28]), and possibly with corticosteroid use. Anti-TNF therapy was not associated with ischemic stroke (P = 0.584, OR 0.80 [95% CI 0.34-1.82]). CONCLUSION: RA is associated with increased risk of stroke, particularly ischemic stroke. Stroke is predicted by RA severity, certain cardiovascular risk factors, and comorbidity. Except for rofecoxib, RA treatment does not appear to be associated with stroke, although the effect of corticosteroids remains uncertain.