Cancer in biopsy-proven giant cell arteritis. A population-based study

OBJECTIVE: To investigate the potential association between giant cell arteritis (GCA) and cancer in a series of consecutive patients diagnosed with biopsy-proven GCA over a 25-year period at the single reference hospital for a well-defined population. METHODS: The case records of all patients diagnosed with biopsy-proven GCA at the Department of Medicine of the Hospital Xeral-Calde (Lugo, Northwest Spain) between January 1, 1981 and December 31, 2005 were reviewed. Information on cancer and cause of death over the extended follow-up was assessed. In all cases the presence of cancer was histologically confirmed. RESULTS: Cancer was found in 39 (15.3%) of the 255 GCA patients. Although 7 (18%) of the 39 patients had cancer either at the time or within the first 12 months after GCA diagnosis, the standardized mortality ratio (SMR) due to cancer in patients with biopsy-proven GCA showed no increase (overall SMR 1.06 [0.65-1.60]; men, 0.81; women, 1.50). The time interval between GCA diagnosis and cancer diagnosis was 5.2+/-3.8 years (median 4.2 years; interquartile range: 3-7 years). When multivariate analysis adjusted by age and sex was performed, only the presence of dysphagia (adjusted hazards ratio (HR)=3.90; P=0.04), abnormal temporal artery on physical examination (adjusted HR=4.61; P=0.04), and anemia at the time of GCA diagnosis (adjusted HR=3.39; P=0.01) were associated with an increased risk of cancer over the extended follow-up. CONCLUSION: The results from this series do not support an overall increase of mortality due to cancer in GCA.     

Aortic aneurysm and dissection in patients with biopsy-proven giant cell arteritis from northwestern Spain: a population-based study

Most classical manifestations of giant cell arteritis (GCA) are the result of occlusive vascular involvement. However, unlike ischemic manifestations, aortic aneurysmal disease in patients with GCA has been less well described. We assessed the incidence and predictors of aortic aneurysm and dissection in patients with biopsy-proven GCA from the Lugo region of northwestern Spain and compared the results with those in a 2003 report from Olmsted County, MN. We performed a retrospective study of biopsy-proven GCA patients diagnosed from 1981 to 2001 at the single hospital for a well-defined population of almost 250,000 people. Twenty (9.5%) of the 210 biopsy-proven GCA patients diagnosed during the study period developed aortic aneurysmal disease. Sixteen of the 20 patients had thoracic aneurysms and 6 had abdominal aneurysms. The incidence of aortic aneurysm and/or dissection in Lugo (18.9 per 1000 person years at risk) was similar to that reported in Olmsted County (18.7 per 1000 person years at risk). Hypertension (hazard ratio: 4.73) and polymyalgia rheumatica with a marked acute inflammatory response at the time of diagnosis of GCA (hazard ratio: 3.71) were the best predictors of aortic aneurysmal disease. Our present observations suggest that a severe inflammatory response associated with hypertension at the time of diagnosis of GCA may promote the development of aortic aneurysmal disease. GCA patients having these features should be monitored for the existence of aortic aneurysm and dissection.     

Giant cell arteritis in northwestern Spain: a 25-year epidemiologic study

To continue our investigation of the epidemiology of giant cell arteritis (GCA) in southern Europe, we assessed the potential presence of trends, peaks, and fluctuations in the incidence of this vasculitis over a 25-year period in the Lugo region of northwestern Spain. We also sought to determine whether changes in the clinical spectrum of the disease existed. From 1981 to 2005, biopsy-proven GCA was diagnosed in 255 Lugo residents. The age- and sex-adjusted annual incidence rate was 10.13 (95% confidence interval [CI], 8.93-11.46) per 100,000 population aged 50 years and older. The mean age +/- SD at the time of diagnosis was 75.0 +/- 6.9 years. The annual incidence rate in women (10.23; 95% CI, 8.60-12.08) was slightly greater than that in men (9.92; 95% CI, 8.19-11.89) (p = 0.15). The annual incidence rate increased with advancing age up to a maximum of 23.16 (95% CI, 19.52-27.28) in the 70-79 year age-group. A progressive increase in the incidence was observed from 1981 through 2000 (p = 0.001). However, the age- and sex-adjusted incidence rate for biopsy-proven GCA in the Lugo region did not show peaks in the annual incidence of GCA. Likewise, we observed no seasonal pattern for the diagnosis of the disease. Visual ischemic manifestations and irreversible visual loss were observed in 57 (22.4%) and 32 (12.5%) of the 255 patients, respectively. A negative trend manifested by a progressive decline in the number of patients with visual ischemic manifestations (p = 0.021) or permanent visual loss (p = 0.018) was found over the 25-year period of study. The decline in the frequency of visual manifestations of GCA could not be attributed to a shorter delay to diagnosis, as no significant differences were observed when the delays to diagnosis in the 5 consecutive 5-year periods were compared. In conclusion, the current study confirms a progressive increase in the incidence of biopsy-proven GCA in northwestern Spain, and suggests that there has been a change in the clinical spectrum of the disease.     

Influence of age,sex, and place of residence on clinical expression of giant cell arteritis in northwest Spain

OBJECTIVE: To investigate the epidemiology of giant cell arteritis (GCA), we examined whether differences in clinical and laboratory features exist in patients with biopsy-proven GCA from Northwest Spain according to sex, place of residence, and age at disease onset. METHODS: Retrospective study of biopsy-proven GCA diagnosed from January 1, 1981, to December 31, 2001, at the single hospital for a well defined population of 250,000. A comparative analysis was conducted of clinical and laboratory features according to sex, place of residence (rural or urban), and age at the onset of symptoms (< 70 yrs; >or= 70 yrs). RESULTS: Between 1981 and 2001, 210 patients from the Lugo region were diagnosed with biopsy-proven GCA. In urban areas GCA was significantly more common in women (rate ratio 1.58, 95% CI 1.00-2.53, p = 0.05). Women presented manifestations of polymyalgia rheumatica (PMR) more commonly than men. However, no statistically significant difference in the frequency of visual manifestations or permanent visual loss were observed between the sexes. GCA was slightly more common in rural than in urban areas (annual adjusted incidence rate in rural areas 10.4/100,000 in people age >or= 50 years vs 9.1/100,000 in urban areas; p = 0.34). GCA was more common among men in rural areas (rate ratio 1.73, 95% CI 1.10-2.70, p = 0.02). Patients younger than 70 years at the time of diagnosis (20%) had a trend to a longer delay to diagnosis and a marginal increase in the frequency of PMR compared with those with disease onset at age >or= 70 years. A higher inflammatory response was observed in the patients younger than 70 years. CONCLUSION: In patients with biopsy-proven GCA from Northwest Spain PMR manifestations are more commonly observed in women. The higher inflammatory response and the longer delay to diagnosis in younger patients call for a higher physician awareness of this vasculitis among individuals younger than 70 years.     

Macro and microvascular complications are determinants of increased infection-related mortality in Brazilian type 2 diabetes mellitus patients

OBJECTIVE: To investigate infection-related mortality and its predictors in Brazilian type 2 diabetic patients. METHODS: It was carried out a long-term prospective study with 471 type 2 diabetic outpatients. Several clinical, laboratory and electrocardiographic variables were recorded at baseline. Predictive factors for infection-related mortality were evaluated by Kaplan-Meyer estimation of survival curves, univariate and multivariate Cox survival analysis. Excess infection-related mortality in this cohort was evaluated by comparing its rate with that of the Rio de Janeiro background population and calculating standardized mortality rates (SMR). RESULTS: During a median follow up of 57 months (range: 1-86 months), 40 (33.1%) patients died from infection-related causes. After adjusting for age and sex, the infection-related SMR was 6.6 (95% confidence interval [95% CI]: 4.8-9.0). In Cox multivariate analysis the predictors of infection-related mortality were older age (hazard ratio [HR]: 1.91; 95% CI: 1.35-2.70), pre-existing peripheral arterial disease (HR: 3.86; 95% CI: 1.80-8.28) and cerebrovascular disease (HR: 3.28; 95% CI: 1.24-8.70), lower HDL-cholesterol (HR: 2.50; 95% CI: 1.32-4.74) and increased 24h-proteinuria (HR: 1.22; 95% CI: 1.08-1.37). After excluding patients with peripheral and cerebrovascular disease at baseline, neuropathy and coronary heart disease were selected as predictors of mortality, besides older age and proteinuria. CONCLUSIONS: Brazilian type 2 diabetic patients have a six-fold excess infection-related mortality than the general population. This increased mortality is mainly determined by the presence of micro and macrovascular complications. Multifactorial risk interventions are needed in order to decrease this burden of infection-related mortality.     

Epidemiology of biopsy proven giant cell arteritis in northwestern Spain: trend over an 18 year period

OBJECTIVE: In Europe giant cell arteritis (GCA) is more common in Scandinavian countries than in southern regions. Epidemiological studies on GCA in other more distant countries have indicated a progressive increase in incidence. A regular cyclical pattern in incidence of GCA over 20 years has been reported in Olmsted County (Minnesota, USA). In contrast, no cyclical fluctuation has been recently reported in Sweden. To investigate further the epidemiology of GCA in southern Europe the trend in incidence and fluctuations of this vasculitis over 18 years in the Lugo region of northwestern Spain were examined. METHODS: A retrospective study of biopsy proven GCA diagnosed between 1 January 1981 and 31 December 1998 at a single hospital for a well defined population of almost 250 000 people. Annual incidence was calculated for the whole group of patients and for men and women separately. Monthly variations, annual peaks of incidence, and trend in the incidence of biopsy proven GCA with and without polymyalgia rheumatica (PMR) were also examined. RESULTS: One hundred and sixty one Lugo residents were diagnosed with biopsy proven GCA between 1981 and 1998. The average annual incidence for the population aged 50 and older was 10.24/100 000 (men 11.00/100 000, women 9.57/100 000). A progressive increase in the incidence in both men and women was seen. In men there was an annual increase of 8% (95% CI 4% to 13%; p<0.0001). In women the annual increase was 11% (95% CI 5% to 17%; p<0.0001). The overall annual increase for men and women was 10% (95% CI 6% to 14%; p<0.0001). No seasonal pattern or peaks in the incidence were seen. During the period 1981-94 GCA was more common in men than in women. In contrast, during the last years of study the increase in incidence was higher in women. In women the annual ratio of incidence of GCA with PMR/incidence of GCA without PMR was generally higher than 1. However, in men the annual ratio was initially 1 but decreased gradually, indicating a progressive decrease in the proportion of men with biopsy proven GCA associated with PMR. CONCLUSION: In northwestern Spain there has been a progressive increase in GCA incidence. As seen in other countries where GCA is more common, during the past few years the increase in incidence has been mainly due to a higher number of new cases in women.     

Interferon treatment improves survival in chronic hepatitis C patients showing biochemical as well as virological responses by preventing liver-related death

Interferon therapy for chronic hepatitis C reduces the risk of hepatocellular carcinoma, especially among virological and biochemical responders. However, little is known about the effect of interferon therapy on mortality. We studied the long-term effect of interferon therapy on mortality in patients with chronic hepatitis C. For this retrospective cohort study, 2954 patients with chronic hepatitis C were recruited, of whom 2698 received interferon therapy and 256 did not. The effect of interferon therapy on survival was assessed by standardized mortality ratio (SMR) based on published mortality data for the general Japanese population and by risk ratio calculated by proportional hazard regression. Over 6.0 +/- 2.2 years follow-up, death from liver-related diseases was observed in 69 (68%) of 101 deaths among interferon-treated patients and in 42 (81%) of 52 deaths among untreated patients. Compared with the general population, overall mortality was high among untreated patients (SMR: 2.7; 95% CI: 2.0-3.6) but not among interferon-treated patients (SMR: 0.9; 95% CI: 0.7-1.1). Liver-related mortality was extremely high among untreated patients (SMR: 22.2; 95% CI: 16.0-30.0) and less among interferon-treated patients (SMR: 5.5; 95% CI: 4.3-6.9). The risk of death from all causes was lower for interferon-treated than untreated patients (risk ratio: 0.47; 95% CI: 0.261-0.836; P = 0.01). The risk of death from liver-related diseases was significantly lower for sustained virological responders (risk ratio: 0.04; 95% CI: 0.005-0.301; P = 0.002) compared with untreated patients, but not for nonsustained virological responders. Sustained biochemical responders (risk ratio: 0.03; 95% CI: 0.004-0.230; P < 0.001) and transient biochemical responders (risk ratio: 0.18; 95% CI: 0.063-0.532; P = 0.002) showed a significantly reduced risk of death from liver-related death, whereas biochemical nonresponders did not. Hence interferon treatment improved survival in chronic hepatitis C patients showing a biochemical as well as a virological response by preventing liver-related deaths.     

Giant cell arteritis without clinically evident vascular involvement in a defined population

OBJECTIVES: To examine the frequency and clinical presentation of biopsy-proven giant cell arteritis (GCA) patients who do not exhibit overt clinical vascular manifestations. To assess whether differences exist between this group of patients and the rest of biopsy-proven GCA patients. METHODS: Retrospective study of biopsy-proven GCA patients diagnosed from 1981 through 2001 at the single hospital for a well-defined population of almost 250,000 people. Patients were considered as having no evident vascular involvement if cranial ischemic manifestations or other vascular complications of GCA were not present at the time of diagnosis or during at least 12 months' followup. RESULTS: Between 1981 and 2001, 210 patients from the Lugo region of northwest Spain were diagnosed with biopsy-proven GCA. Eleven patients did not show overt vascular manifestations of GCA. Nine of them presented with polymyalgia rheumatica (PMR) and another 2 fulfilled criteria for fever of unknown origin. Patients without clinically evident vascular involvement had a significantly longer delay to diagnosis than those with vascular manifestations. Also, PMR manifestations were more frequently observed in this group of patients. CONCLUSIONS: Biopsy-proven GCA without clinically evident vascular involvement is not exceptional. Despite having a longer delay to diagnosis, these patients constitute a more benign subgroup of GCA.     

Excess mortality in giant cell arteritis

A 13-year departmental sample of 34 patients with definite (biopsy-verified) giant cell arteritis (GCA) was reviewed. The mortality of this material was compared to sex-, age- and time-specific death rates in the Danish population. The standardized mortality ratio (SMR) was 1.8 (95% confidence limits, 1.1-2.8). During the same period 146 patients with probable (not biopsied, but clinically diagnosed in the department) GCA and 85 cases of possible (diagnosed and treated before admission) GCA had been admitted to the department. Those two groups did not differ from the biopsy-verified group with respect to SMR, sex distribution or age. In the group of patients with department-diagnosed GCA (definite + probable = 180 patients), the 95% confidence interval for the SMR of the women included 1.0. In all other subgroups there was a significant excess mortality. Excess mortality has been found in two of seven previous studies on survival in GCA. The prevailing opinion that steroid-treated GCA does not affect the life expectancy of patients is probably not correct.     

AIDS mortality trends in Mexico, 1988-1997

OBJECTIVE: To assess the geographic distribution and trends of AIDS deaths for the 1988-1997 period in Mexico. MATERIAL AND METHODS: Crude and adjusted mortality rates were estimated for the 1988-1997 period. A trend test was performed using the simple linear regression method. Standardized mortality ratios (SMR) and years of potential life lost (YPLL) were calculated for each Mexican state. RESULTS: During the study period (1988-1997), there were 26,999 AIDS deaths in Mexico; 86.5% (23,354) of them were among men. The mean age at the time of death was 38.4 years for men and 37.7 years for women (p > 0.05). The crude AIDS mortality rate for the period of study was 3.02 cases (95% CI: 2.94, 3.06) per 100,000 inhabitants. The adjusted rate was 3.13 (95% CI: 3.09, 3.17), with 5.22 (95% CI: 5.16-5.29) for men and 0.82 (95% CI: 0.79-0.84) for women. The states with the highest SMR were: Baja California (SMR: 248.69; 95% CI: 234.02-263.36), Mexico City (SMR: 220.74; 95% CI: 215.57-225.91), and Jalisco (SMR: 169.16; 95% CI: 162.88-175.44). Similarly, a Potential Lost Life Years Index (PLLYI) analysis by state showed a greater risk of premature AIDS mortality in the same states [Baja California (PLLYI index: 236.33; 95% CI: 233.97-238.68), Mexico City (PLLYI: 194.68; 95% CI: 193.88-195.48), and Jalisco (PLLYI: 170.69; 95% CI: 169.60-171.79)]. CONCLUSIONS: Mortality trends indicate that AIDS mortality in Mexico increased by an annual rate of 23% between 1988 and 1997. The adjusted AIDS mortality rate increased from 0.75 per 100,000 in 1988, to 4.20 per 100,000 in 1997, with the largest burden of mortality in men (male to female ratio of 6:1). We therefore expect that a decreasing effect on AIDS mortality trends will be observed in the next years. The English version of this paper is available too at: http://www.insp.mx/salud/index.html.     

The prevalence and incidence of biopsy-proven lupus nephritis in the UK: Evidence of an ethnic gradient

OBJECTIVE: Renal involvement is a major complication of systemic lupus erythematosus (SLE) and is a strong determinant of morbidity and mortality. There have been no previous studies of the epidemiology of lupus nephritis. Our aim was to establish the prevalence and incidence of biopsy-proven lupus nephritis in the northwest of England in 2001 and to examine the influence of age, sex, and ethnicity. METHODS: Adults (age 18 years and older) with biopsy-proven lupus nephritis were identified from 5 sources: renal biopsy databases, dialysis/transplant databases, nephrologists' patients, clinic lists, and lupus patient groups. The denominator data for the northwest of England were ascertained from the 2001 census. RESULTS: We identified 208 cases of biopsy-proven lupus nephritis (176 women, 32 men): the overall prevalence was 4.4 per 100,000 population (95% confidence interval [95% CI] 3.8-5.0), 7.1 per 100,000 (95% CI 6.1-8.2) in women, and 1.4 per 100,000 (95% CI 1.0-2.0) in men. The prevalence was significantly higher among women in the ethnic subgroups: 110.3 per 100,000 population (95% CI 55.0-197.3) in Chinese patients, 99.2 per 100,000 (95% CI 55.5-163.6) in Afro-Caribbean, 21.4 per 100,000 (95% CI 12.0-35.2) in Indo-Asian (Asians from the Indian subcontinent), and 5.6 per 100,000 (95% CI 4.7-6.7) in white patients. The overall annual incidence rate was 0.40 per 100,000 population per year (95% CI 0.24-0.63), with a rate of 0.68 (95% CI 0.40-1.10) in women and 0.09 (95% CI 0.01-0.32) in men. Capture-recapture methods did not suggest any additional cases. CONCLUSION: This first estimate of the prevalence and incidence of biopsy-proven lupus nephritis demonstrates dramatic differences in prevalence according to ethnicity, with an increasing gradient from the white to the Indo-Asian, Afro-Caribbean, and Chinese populations.     

Prognosis of Chronic Pancreatitis: An International Multicenter Study

Objectives: Tbe aim of this study was to determine which factors predict mortality in a cobort of patients with cbronic alcoholic and nonalcoholic pancreatitis. Patients with chronic pancreatitis are known to have a reduced life expectancy, but the quantitative relationship between various clinical features and survival is unclear. Methods: We evaluated survival among 2015 subjects with chronic pancreatitis treated at seven centers located in six countries. Results: Mean age at diagnosis was 46 ± 13 yr and mean duration of follow-up was 7.4 ± 6.2 yr. Overall survival at 10 yr was 70% (95% confidence interval (CI), 68–73%) and at 20 yr was 45% (95% CI, 41–49%). Survival was significantly less than in the background population. There were 559 deaths observed among those with chronic pancreatitis compared with an expected number of 157.4, yielding a standardized mortality ratio (SMR) of 3.6 (95% CI, 3.3–3.9). Older subjects and those with alcoholic pancreatitis had a significant reduction in survival. In a mul-tivariate analysis, mortality of middle-aged and older subjects was 2.3 (95% CI, 1.8–2.8) and 6.3 (95% CI, 4.7–8.3) times greater than subjects less than 40 yr at diagnosis. Smoking (hazard ratio, 1.4; 95% CI, 1.0–1.9), drinking (hazard ratio, 1.6; 95% CI, 1.2–2.2), or development of cirrhosis (hazard ratio, 2.5; 95% CI, 2.0–3.2) increased the risk of death during the observation period, but we observed no survival difference in operated vs . nonoperated patients. Conclusions: Age at diagnosis, smoking, and drinking are major predictors of mortality in patients with chronic pancreatitis.     

Fever in biopsy-proven giant cell arteritis: clinical implications in a defined population

OBJECTIVE: To assess the frequency and clinical features of biopsy-proven giant cell arteritis (GCA) patients who had fever at the time of diagnosis of the disease, and the relationship between fever, ischemic complications, and the systemic inflammatory response in GCA. METHODS: A retrospective study of biopsy-proven GCA patients diagnosed between 1981 and 2001 was performed at the single referral hospital for a well-defined population in the Lugo region of northwest Spain. Patients were considered as having fever if the axillary temperature at the time of admission or during the followup prior to the onset of corticosteroid therapy was > or =38 degrees C. RESULTS: During the period of study, 21 (10%) of the 210 biopsy-proven GCA patients had fever. Two of them fulfilled criteria for fever of unknown origin. Patients with fever had a lower frequency of severe ischemic manifestations than the rest of biopsy-proven GCA patients. They also exhibited a more severe inflammatory disease, with significant abnormality in most laboratory variables, including higher elevation of erythrocyte sedimentation rate, lower values of hemoglobin, and higher proportion of patients with increased alkaline phosphatase. By logistic regression analysis, we observed that patients with fever had an increased risk of developing anemia (odds ratio [OR] 12.24). In contrast, a negative association between severe ischemic manifestations and fever was found (OR 0.41). CONCLUSION: Biopsy-proven GCA patients with fever constitute a subgroup of patients with more severe inflammatory response and less ischemic disease.     

Decreasing mortality in patients with rheumatoid arthritis: results from a large population based cohort in Sweden, 1964-95

OBJECTIVE: To assess changes in mortality in patients with rheumatoid arthritis (RA) from 1964 to 1995. METHODS: A population based cohort of 46,917 patients with RA was identified from 1964 to 1994, using the Swedish Hospital Discharge Register, and followed until 1995 through linkage to the Cause of Death Register. Mortality was separately analyzed in each inclusion period (1964-75, 1975-84, 1985-94). The relative risk of death was estimated as standardized mortality ratio (SMR) using the Swedish population as a reference RESULTS: All-cause mortality was increased twice the expected (SMR = 2.03, 95% CI 2.00, 2.05). Coronary artery disease was the major cause of death and mortality was increased by 80% (SMR = 1.79, 95% CI 1.75, 1.83). Females with RA aged 20-39 at first discharge had a more than 5-fold increased risk of coronary death (SMR = 5.48, 95% CI 3.45-5.71). From 1975 patients with RA had decreasing all-cause mortality. This decline was most pronounced in patients aged 40-59 at first discharge, where SMR was 2.68 (95% CI 2.45, 2.92) from 1964 to 1974 compared to SMR 1.63 (95% CI 1.37, 1.92) from 1985 to 1994. CONCLUSION: The elevated mortality rates in RA patients compared to the general population have decreased during the last 20 years, possibly due to an increased access to specialized rheumatology care. An excess risk for death in coronary artery disease was, however, present in RA patients, especially patients with early onset of disease.     

Geographical and genetic factors do not account for significant differences in the clinical spectrum of giant cell arteritis in southern europe

OBJECTIVE: To investigate whether genetic and geographical differences may influence the clinical spectrum of giant cell arteritis (GCA), we compared the demographic and clinical features of patients with biopsy-proven GCA from Reggio Emilia (Northern Italy) and Lugo (Northwest Spain) during a 15-year period. METHODS: We performed a retrospective review of the case records of all patients diagnosed with biopsy-proven GCA at Hospital Xeral-Calde (Lugo, Spain) and Hospital Santa Maria Nuova (Reggio Emilia, Italy) between 1 January 1986 and 31 December 2001. Both hospitals are the only referral centers for populations living in central Galicia and central Emilia Romagna, respectively. RESULTS: During the period of study, 194 Lugo residents and 126 Reggio Emilia residents were diagnosed with biopsy proven GCA. Reggio Emilia patients were more likely to be female (74% vs 54%; p = 0.0001). Although Lugo patients complained of headache (86%) more commonly than did those from Reggio Emilia (77%), the difference was only marginally significant (p = 0.05). The proportion of patients with visual manifestations or visual loss was remarkably similar (22% for visual manifestations and 17% for visual loss in Lugo and 29% and 21% for Reggio Emilia residents). The mean erythrocyte sedimentation rate prior to the onset of therapy was also similar. CONCLUSION: Apart from differences in sex, the clinical spectrum of GCA in these 2 Southern European regions was similar.     

Systemic lupus erythematosus in northwestern Spain: a 20-year epidemiologic study

To further investigate the epidemiology of systemic lupus erythematosus (SLE) in southern Europe, we assessed the incidence, prevalence, clinical spectrum of the disease, flares, and survival of patients diagnosed with SLE in the Lugo region of northwestern Spain. Between January 1987 and December 2006, 150 Lugo residents were diagnosed as having SLE according to the 1982 American College of Rheumatology criteria for the classification of SLE. Women outnumbered men (127 [84.7%] vs. 23 [15.3%]). The mean age at the time of disease diagnosis was 46.1 ± 19.6 years. The mean follow-up from the time of disease diagnosis was 7.8 ± 4.5 years. The age- and sex-adjusted annual incidence rate over the 20-year study period was 3.6 (95% confidence interval [CI], 3.0-4.2) per 100,000 population aged 15 years and older. The overall annual incidence rate over the 20-year study period in women (5.9/100,000 population aged ≥ 15 yr; 95% CI, 4.9-7.0) was higher than in men (1.1/100,000 population aged ≥ 15 yr; 95% CI, 0.7-1.7) (p < 0.001). By December 31, 2006, the overall age-adjusted SLE prevalence in the Lugo region for patients who fulfilled at least 4 of 1982 American College of Rheumatology criteria was 17.5 per 100,000 population aged 15 years and older (95% CI, 12.6-24.1). Prevalence in women (29.2/100,000 population aged ≥ 15 yr; 95% CI, 20.0-40.7) was higher than in men (5.8/100,000 population aged ≥ 15 yr; 95% CI, 2.0-12.0). The most frequent clinical manifestation was arthritis. As reported in population-based studies on SLE patients of European descent, renal disease was observed in only 27.3% of the patients. The rate of flares was 0.084/year. A younger age and the presence of nephritis at the time of disease diagnosis were associated with the development of flares during the follow-up of Lugo patients. Compared with the general population the probability of survival in patients with SLE was significantly reduced (p = 0.04). In conclusion, the present study establishes a baseline estimate of the incidence and clinical spectrum of SLE in northwestern Spain. According to our results, the incidence of SLE in northwestern Spain is slightly higher than that reported in most European regions. Patients with SLE from northwestern Spain have a later average age onset and a lower frequency of nephritis than in the African-American population. However, our data show a reduced probability of survival in Spanish patients with SLE.     

Giant cell arteritis: disease patterns of clinical presentation in a series of 240 patients

Classically, patients with giant cell arteritis (GCA) present with cranial ischemic manifestations that are directly related to vascular involvement. However, a variable proportion of GCA patients may present without obvious vascular manifestations. Since a high index of suspicion of this condition in individuals over the age of 50 years is needed to prevent the development of severe complications, we have studied the different patterns of disease presentation in a series of 240 patients with biopsy-proven GCA diagnosed at the single hospital for the well-defined population of Lugo, Spain, between January 1, 1981, and June 15, 2004. During the study period, 203 (86.4%) GCA patients presented with headache. Patients with headache were found to have an abnormal temporal artery on physical examination more commonly than the other GCA patients (79.8% versus 35.1%; p < 0.001). Compared with the other GCA patients, those who presented with polymyalgia rheumatica (PMR) were younger (73.4 +/- 6.3 versus 75.6 +/- 6.9 yr; p = 0.013) and had a longer delay to diagnosis (13.4 +/- 12.2 versus 8.3 +/- 10.0 wk; p = 0.013). One hundred thirty-one (54.6%) patients presented with severe ischemic manifestations. Abnormal temporal artery on physical examination (odds ratio, 2.25) and anemia at the time of disease diagnosis (odds ratio, 0.53) were found to be the best predictors for severe ischemic manifestations of GCA. Eighteen (7.5%) patients presented without overt ischemic manifestations of GCA. Patients younger than 70 years of age at the time of diagnosis had a longer delay to diagnosis and exhibited PMR more commonly than older patients. Our observations confirm the presence of different disease patterns of clinical presentation in GCA and emphasize the importance of an abnormal temporal artery on physical examination and anemia as factors that may predict the risk of severe ischemic complications related to GCA.     

Renal dysfunction predicts attenuation of ischemic heart disease mortality risk from elevated glucose among treated hypertensive patients

BACKGROUND: Impaired fasting glucose (IFG) and renal dysfunction are recognized as independent risk factors for adverse heart outcomes. This study examines the interaction of renal dysfunction and IFG (>or=110 mg/dL) upon the risk of ischemic heart disease (IHD) mortality among treated hypertensive subjects. METHODS: Subjects were 9918 participants in a worksite-based antihypertensive treatment program in New York City (1981 to 1999) with baseline estimated glomerular filtration rate (GFR) >30 mL/min/1.73 m2 (estimated by Cockcroft and Gault formula) observed for a mean follow-up of 9.6 +/- 5.0 years (range 0.5-20.0 years). Outcome events were IHD deaths (n = 337) ascertained from the National Death Index. Cox proportional hazard models were constructed for the entire cohort to assess the interaction and then stratified by moderate renal dysfunction (MRD; GFR 60-30 mL/min/1.73 m2). Age and sex adjusted rates were calculated within MRD and NKF-defined categories. Hazard ratios for IFG were calculated within MRD strata. RESULTS: The interaction product term of MRD and IFG significantly improved (P = .001) a Cox proportional hazard model after adjusting for known cardiovascular risk factors. Among participants with GFR >or=60 mL/min/1.73 m2 the IHD mortality hazard ratio for IFG was 1.47 (95% CI = 1.09-1.99; P = .012). Conversely, among participants with MRD, the IHD mortality hazard ratio for IFG was 0.44 (95% CI = 0.21-0.94; P = .034). CONCLUSIONS: These results suggest an attenuating effect modification of GFR on IHD mortality risk associated with IFG among treated hypertensive subjects. Whether the observed qualitative interaction is simply statistical or reflects a biological counter-regulatory mechanism requires additional study.     

Association of a functional inducible nitric oxide synthase promoter variant with susceptibility to biopsy-proven giant cell arteritis

OBJECTIVE: To assess the contribution of 2 polymorphisms within the inducible nitric oxide (NOS2A) promoter region to susceptibility to giant cell arteritis (GCA). METHODS: One hundred three patients with biopsy-proven GCA and 198 ethnically matched controls from the Lugo region (Northwest Spain) were studied. Patients and controls were genotyped using polymerase chain reaction techniques for a multiallelic (CCTTT)n and for the TAAA repeat polymorphism in the promoter region of the NOS2A gene. RESULTS: No significant differences in allele or genotype frequencies for the (CCTTT)n repeat polymorphism in the NOS2A gene between patients with GCA and controls were observed. However, significant differences for the TAAA repeat polymorphism between patients and controls were found. The overall distribution of NOS2A TAAA genotypes in patients with biopsy-proven GCA was significantly different than controls (p = 0.026). Patients with GCA had an increased frequency of the NOS2A TAAA+ allele (16.5%) compared with controls (9.1%) (p = 0.007; OR 1.98; 95% CI 1.20-3.27). This was due to an increased frequency of both heterozygotes (27.2%) and homozygotes (2.9%) for NOS2A TAAA+ observed in patients compared to controls (15.2% and 1.5%, respectively) (p = 0.007; OR 2.15; 95% CI 1.23-3.78). CONCLUSION: Our results suggest a potential implication for NOS2A TAAA gene polymorphism in GCA susceptibility.     

Body mass index, playing position, race, and the cardiovascular mortality of retired professional football players

Concern exists about cardiovascular disease (CVD) in professional football players. We examined whether playing position and size influence CVD mortality in 3,439 National Football League players with ≥ 5 pension-credited playing seasons from 1959 to 1988. Standardized mortality ratios (SMRs) compared player mortality through 2007 to the United States population of men stratified by age, race, and calendar year. Cox proportional hazards models evaluated associations of playing-time body mass index (BMI), race, and position with CVD mortality. Overall player mortality was significantly decreased (SMR 0.53, 95% confidence interval [CI] 0.48 to 0.59) as was mortality from cancer (SMR 0.58, 95% CI 0.46 to 0.72), and CVD (SMR 0.68, 95% CI 0.56 to 0.81). CVD mortality was increased for defensive linemen (SMR 1.42, 95% CI 1.02 to 1.92) but not for offensive linemen (SMR 0.70, 95% CI 0.45 to 1.05). Defensive linemen's cardiomyopathy mortality was also increased (SMR 5.34, 95% CI 2.30 to 10.5). Internal analyses found that CVD mortality was increased for players of nonwhite race (hazard ratio 1.69, 95% CI 1.13 to 2.51). After adjusting for age, race, and calendar year, CVD mortality was increased for those with a playing-time BMI ≥ 30 kg/m2 (hazard ratio 2.02, 95% CI 1.06 to 3.85) and for defensive linemen compared to offensive linemen (hazard ratio 2.07, 95% CI 1.24 to 3.46). In conclusion, National Football League players from the 1959 through 1988 seasons had decreased overall mortality but those with a playing-time BMI ≥ 30 kg/m2 had 2 times the risk of CVD mortality compared to other players and African-American players and defensive linemen had higher CVD mortality compared to other players even after adjusting for playing-time BMI.