Trends in heart failure incidence and survival in a community-based population

Context  The epidemic of heart failure has yet to be fully investigated, and data on incidence, survival, and sex-specific temporal trends in community-based populations are limited. Objective  To test the hypothesis that the incidence of heart failure has declined and survival after heart failure diagnosis has improved over time but that secular trends have diverged by sex. Design, Setting, and Participants  Population-based cohort study using the resources of the Rochester Epidemiology Project conducted in Olmsted County, Minnesota. Patients were 4537 Olmsted County residents (57% women; mean [SD] age, 74 [14] years) with a diagnosis of heart failure between 1979 and 2000. Framingham criteria and clinical criteria were used to validate the diagnosis Main Outcome Measures  Incidence of heart failure and survival after heart failure diagnosis. Results  The incidence of heart failure was higher among men (378/100 000 persons; 95% confidence interval [CI], 361-395 for men; 289/100 000 persons; 95% CI, 277-300 for women) and did not change over time among men or women. After a mean follow-up of 4.2 years (range, 0-23.8 years), 3347 deaths occurred, including 1930 among women and 1417 among men. Survival after heart failure diagnosis was worse among men than women (relative risk, 1.33; 95% CI, 1.24-1.43) but overall improved over time (5-year age-adjusted survival, 43% in 1979-1984 vs 52% in 1996-2000, P<.001). However, men and younger persons experienced larger survival gains, contrasting with less or no improvement for women and elderly persons. Conclusion  In this community-based cohort, the incidence of heart failure has not declined during 2 decades, but survival after onset of heart failure has increased overall, with less improvement among women and elderly persons.      

Temporal trends in infective endocarditis: a population-based study in Olmsted County, Minnesota

Context  Limited data exist regarding population-based epidemiologic changes in incidence of infective endocarditis (IE). Objective  To evaluate temporal trends in the incidence and clinical characteristics of IE. Design, Setting, and Patients  Population-based survey using the resources of the Rochester Epidemiology Project of Olmsted County, Minnesota. One hundred seven IE episodes occurred in 102 Olmsted County residents between 1970 and 2000. The modified Duke criteria were used to validate the diagnosis of definite or possible IE. Main Outcome Measures  Incidence of IE, proportion of patients with underlying heart disease, and causative microorganisms and clinical characteristics. Results  Age- and sex-adjusted incidence of IE ranged from 5.0 to 7.0 cases per 100 000 person-years during the study period and did not change significantly over time (P = .42 for trend). Infective endocarditis caused by viridans group streptococci was the most common organism-specific subgroup, with an annual adjusted incidence of 1.7 to 3.5 cases per 100 000; in comparison, IE due to Staphylococcus aureus had an annual adjusted incidence of 1.0 to 2.2 cases per 100 000. No time trend was detected for either pathogen group (P = .63 and P = .66, respectively). An increasing temporal trend was observed in the proportions of prosthetic valve IE cases (P = .09). Among people with underlying heart disease, there was an increasing temporal trend in mitral valve prolapse (P = .04) and a decreasing trend in rheumatic heart disease (P = .08). However, the absolute numbers were small. There was no time trend in rates of valve surgery or 6-month mortality during the study period (P = .97 and P = .59, respectively). Conclusions  In this community-based temporal trend study, we found no substantial change in the incidence of IE over the past 3 decades. Viridans group streptococci continue to outnumber S aureus as the most common causative organisms of IE in this population.      

Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years

Context  Prior estimates of long-term trends in the incidence and severity of stroke have varied; trends in lifetime risk have not been reported. Objective  To determine long-term trends in the incidence, lifetime risk, severity, and 30-day mortality of clinical stroke. Design, Setting, and Participants  Prospective evaluation of the community-based Framingham Study original and offspring cohorts. Participants were 9152 men and women free of prevalent stroke and undergoing follow-up for up to 50 years over 3 consecutive periods (1950-1977, 1978-1989, and 1990-2004), with biennial ascertainment of stroke risk factor data and active surveillance for incident clinical stroke and cause-specific mortality. Main Outcome Measures  Incidence (age-adjusted, sex-specific), severity, 30-day mortality, and mortality-adjusted 10-year and lifetime risk of stroke in each of the specified periods. Results  There were 1030 incident clinical strokes (450 [44%] in men, 629 atherothrombotic brain infarctions [61%]) in 9152 persons 55 years or older over 174 917 person-years of follow-up. The age-adjusted incidence of first stroke per 1000 person-years in each of the 3 periods was 7.6, 6.2, and 5.3, respectively, in men (P = .02 for trend) and 6.2, 5.8, and 5.1 in women (P = .01 for trend). The lifetime risk at age 65 years decreased from 19.5% to 14.5% in men (P = .11) and from 18.0% to 16.1% in women (P = .61). Age-adjusted stroke severity did not vary across periods; however, 30-day mortality decreased significantly in men (from 23% to 14%; P = .01) but not significantly in women (from 21% to 20%; P = .32). Conclusions  In this cohort of men and women free of prevalent clinical stroke at initial examination, incidence of stroke has decreased over the past 50 years but the lifetime risk has not declined to the same degree, perhaps due to improved life expectancy. The results of this study suggest that improved control of risk factors has lowered stroke incidence but emphasize the need for continued primary prevention efforts.      

Serotypes of Chlamydia trachomatis and risk for development of cervical squamous cell carcinoma

Context  Human papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown. Objective  To study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC. Design and Setting  Longitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries. Subjects  One hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls. Main Outcome Measure  Risk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels. Results  Of specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1.6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P<.001 for trend). Conclusions  Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.      

Obesity, weight gain, and the risk of kidney stones

Context  Larger body size may result in increased urinary excretion of calcium, oxalate, and uric acid, thereby increasing the risk for calcium-containing kidney stones. It is unclear if obesity increases the risk of stone formation, and it is not known if weight gain influences risk. Objective  To determine if weight, weight gain, body mass index (BMI), and waist circumference are associated with kidney stone formation. Design, Setting, and Participants  A prospective study of 3 large cohorts: the Health Professionals Follow-up Study (N = 45 988 men; age range at baseline, 40-75 years), the Nurses’ Health Study I (N = 93 758 older women; age range at baseline, 34-59 years), and the Nurses’ Health Study II (N = 101 877 younger women; age range at baseline, 27-44 years). Main Outcome Measures  Incidence of symptomatic kidney stones. Results  We documented 4827 incident kidney stones over a combined 46 years of follow-up. After adjusting for age, dietary factors, fluid intake, and thiazide use, the relative risk (RR) for stone formation in men weighing more than 220 lb (100.0 kg) vs men less than 150 lb (68.2 kg) was 1.44 (95% confidence interval [CI], 1.11-1.86; P = .002 for trend). In older and younger women, RRs for these weight categories were 1.89 (95% CI, 1.52-2.36; P<.001 for trend) and 1.92 (95% CI, 1.59-2.31; P<.001 for trend), respectively. The RR in men who gained more than 35 lb (15.9 kg) since age 21 years vs men whose weight did not change was 1.39 (95% CI, 1.14-1.70; P = .001 for trend). Corresponding RRs for the same categories of weight gain since age 18 years in older and younger women were 1.70 (95% CI, 1.40-2.05; P<.001 for trend) and 1.82 (95% CI, 1.50-2.21; P<.001 for trend). Body mass index was associated with the risk of kidney stone formation: the RR for men with a BMI of 30 or greater vs those with a BMI of 21 to 22.9 was 1.33 (95% CI, 1.08-1.63; P<.001 for trend). Corresponding RRs for the same categories of BMI in older and younger women were 1.90 (95% CI, 1.61-2.25; P<.001 for trend) and 2.09 (95% CI, 1.77-2.48; P<.001 for trend). Waist circumference was also positively associated with risk in men (P = .002 for trend) and in older and younger women (P<.001 for trend for both). Conclusions  Obesity and weight gain increase the risk of kidney stone formation. The magnitude of the increased risk may be greater in women than in men.      

Long-term fatty fish consumption and renal cell carcinoma incidence in women

Context  The epidemiological evidence that fatty fish consumption may be associated with the lower risk of several cancers is not consistent and no studies of renal cell carcinoma (RCC) exist. Objective  To examine the association between fatty and lean fish consumption and risk of RCC in women. Design, Setting, and Participants  The Swedish Mammography Cohort, a population-based prospective cohort study of 61 433 women aged 40 to 76 years without previous diagnosis of cancer at baseline (March 1, 1987-December 14, 1990). Participants filled in a food frequency questionnaire at baseline and in September 1997. Main Outcome Measure  Incident renal cell carcinoma. Results  During a mean of 15.3 years (940 357 person-years) of follow-up between 1987 and 2004, 150 incident RCC cases were diagnosed. After adjustment for potential confounders, an inverse association of fatty fish consumption with the risk of RCC was found (P for trend = .02), but no association was found with lean fish consumption. Compared with no consumption, the multivariate rate ratio (RR) was 0.56 (95% confidence interval [CI], 0.35-0.91) for women eating fatty fish once a week or more. Compared with women consistently reporting no fish consumption, the multivariate RR was 0.26 (95% CI, 0.10-0.67) for those women reporting consistent consumption of fatty fish at baseline and 1997 (based on a subset of 36 664 women who filled in the baseline and 1997 questionnaires, with 40 incident RCC cases during the 1998-2004 follow-up period). Conclusion  Our study suggests that consumption of fatty fish may reduce the occurrence of RCC in women.      

Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis

Context  Inconsistent data suggest that endogenous sex hormones may have a role in sex-dependent etiologies of type 2 diabetes, such that hyperandrogenism may increase risk in women while decreasing risk in men. Objective  To systematically assess studies evaluating the association of plasma levels of testosterone, sex hormone–binding globulin (SHBG), and estradiol with risk of type 2 diabetes. Data Sources  Systematic search of EMBASE and MEDLINE (1966-June 2005) for English-language articles using the keywords diabetes, testosterone, sex-hormone-binding-globulin, and estradiol; references of retrieved articles; and direct author contact. Study Selection  From 80 retrieved articles, 43 prospective and cross-sectional studies were identified, comprising 6974 women and 6427 men and presenting relative risks (RRs) or hormone levels for cases and controls. Data Extraction  Information on study design, participant characteristics, hormone levels, and risk estimates were independently extracted by 2 investigators using a standardized protocol. Data Synthesis  Results were pooled using random effects and meta-regressions. Cross-sectional studies indicated that testosterone level was significantly lower in men with type 2 diabetes (mean difference, –76.6 ng/dL; 95% confidence interval [CI], –99.4 to –53.6) and higher in women with type 2 diabetes compared with controls (mean difference, 6.1 ng/dL; 95% CI, 2.3 to 10.1) (P<.001 for sex difference). Similarly, prospective studies showed that men with higher testosterone levels (range, 449.6-605.2 ng/dL) had a 42% lower risk of type 2 diabetes (RR, 0.58; 95% CI, 0.39 to 0.87), while there was suggestion that testosterone increased risk in women (P = .06 for sex difference). Cross-sectional and prospective studies both found that SHBG was more protective in women than in men (P.01 for sex difference for both), with prospective studies indicating that women with higher SHBG levels (>60 vs 60 nmol/L) had an 80% lower risk of type 2 diabetes (RR, 0.20; 95% CI, 0.12 to 0.30), while men with higher SHBG levels (>28.3 vs 28.3 nmol/L) had a 52% lower risk (RR, 0.48; 95% CI, 0.33 to 0.69). Estradiol levels were elevated among men and postmenopausal women with diabetes compared with controls (P = .007). Conclusions  This systematic review indicates that endogenous sex hormones may differentially modulate glycemic status and risk of type 2 diabetes in men and women. High testosterone levels are associated with higher risk of type 2 diabetes in women but with lower risk in men; the inverse association of SHBG with risk was stronger in women than in men.      

Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women

Context  Elevated nonfasting triglycerides indicate the presence of remnant lipoproteins, which may promote atherosclerosis. Objective  To test the hypothesis that very high levels of nonfasting triglycerides predict myocardial infarction (MI), ischemic heart disease (IHD), and death. Design, Setting, and Participants  A prospective cohort study of 7587 women and 6394 men from the general population of Copenhagen, Denmark, aged 20 to 93 years, followed up from baseline (1976-1978) until 2004. Main Outcome Measures  Hazard ratios (HRs) for incident MI, IHD, and total death according to baseline nonfasting triglyceride level categories of 1 to 1.99 mmol/L (88.5-176.1 mg/dL), 2 to 2.99 mmol/L (177.0-264.6 mg/dL), 3 to 3.99 mmol/L (265.5-353.0 mg/dL), 4 to 4.99 mmol/L (354.0-441.6 mg/dL), and 5 mmol/L or more (442.5 mg/dL) vs triglyceride levels of less than 1 mmol/L (<88.5 mg/dL). Results  With increasing levels of nonfasting triglycerides, levels of remnant lipoprotein cholesterol increased. During a mean follow-up of 26 years, 1793 participants (691 women and 1102 men) developed MI, 3479 (1567 women and 1912 men) developed IHD, and 7818 (3731 women and 4087 men) died. For MI, among women, the age-adjusted HRs and multifactorially adjusted HRs (aHRs) for each respective category per 1-mmol/L increase in nonfasting triglyceride levels were 2.2 (aHR, 1.7), 4.4 (aHR, 2.5), 3.9 (aHR, 2.1), 5.1 (aHR, 2.4), and 16.8 (aHR, 5.4); for both, P for trend < .001. For MI, among men, the values were 1.6 (aHR, 1.4), 2.3 (aHR, 1.6), 3.6 (aHR, 2.3), 3.3 (aHR, 1.9), and 4.6 (aHR, 2.4); for both, P for trend < .001. For IHD, among women, the values were 1.7 (aHR, 1.4), 2.8 (aHR, 1.8), 3.0 (aHR, 1.8), 2.1 (aHR, 1.2), and 5.9 (aHR, 2.6); for both, P for trend < .001. For IHD, among men, the values were 1.3 (aHR, 1.1), 1.7 (aHR, 1.3), 2.1 (aHR, 1.3), 2.0 (aHR, 1.2), and 2.9 (aHR, 1.5); P for trend < .001 for age-adjusted and P for trend = .03 for multifactorially adjusted. For total death, among women, the values were 1.3 (aHR, 1.3), 1.7 (aHR, 1.6), 2.2 (aHR, 2.2), 2.2 (aHR, 1.9), and 4.3 (aHR, 3.3); for both, P for trend < .001. For total death, among men, the values were 1.3 (aHR, 1.2), 1.4 (aHR, 1.4), 1.7 (aHR, 1.5), 1.8 (aHR, 1.6), and 2.0 (aHR, 1.8); for both, P for trend < .001. Conclusion  In this general population cohort, elevated nonfasting triglyceride levels were associated with increased risk of MI, IHD, and death in men and women.      

Obesity and the risk of new-onset atrial fibrillation

Context  Obesity is associated with atrial enlargement and ventricular diastolic dysfunction, both known predictors of atrial fibrillation (AF). However, it is unclear whether obesity is a risk factor for AF. Objective  To examine the association between body mass index (BMI) and the risk of developing AF. Design, Setting, and Participants  Prospective, community-based observational cohort in Framingham, Mass. We studied 5282 participants (mean age, 57 [SD, 13] years; 2898 women [55%]) without baseline AF (electrocardiographic AF or arterial flutter). Body mass index (calculated as weight in kilograms divided by square of height in meters) was evaluated as both a continuous and a categorical variable (normal defined as <25.0; overweight, 25.0 to <30.0; and obese, 30.0). In addition to adjusting for clinical confounders by multivariable techniques, we also examined models including echocardiographic left atrial diameter to examine whether the influence of obesity was mediated by changes in left atrial dimensions. Main Outcome Measure  Association between BMI or BMI category and risk of developing new-onset AF. Results  During a mean follow-up of 13.7 years, 526 participants (234 women) developed AF. Age-adjusted incidence rates for AF increased across the 3 BMI categories in men (9.7, 10.7, and 14.3 per 1000 person-years) and women (5.1, 8.6, and 9.9 per 1000 person-years). In multivariable models adjusted for cardiovascular risk factors and interim myocardial infarction or heart failure, a 4% increase in AF risk per 1-unit increase in BMI was observed in men (95% confidence interval [CI], 1%-7%; P = .02) and in women (95% CI, 1%-7%; P = .009). Adjusted hazard ratios for AF associated with obesity were 1.52 (95% CI, 1.09-2.13; P = .02) and 1.46 (95% CI, 1.03-2.07; P = .03) for men and women, respectively, compared with individuals with normal BMI. After adjustment for echocardiographic left atrial diameter in addition to clinical risk factors, BMI was no longer associated with AF risk (adjusted hazard ratios per 1-unit increase in BMI, 1.00 [95% CI, 0.97-1.04], P = .84 in men; 0.99 [95% CI, 0.96-1.02], P = .56 in women). Conclusions  Obesity is an important, potentially modifiable risk factor for AF. The excess risk of AF associated with obesity appears to be mediated by left atrial dilatation. These prospective data raise the possibility that interventions to promote normal weight may reduce the population burden of AF.      

Improved Prognosis of Thoracic Aortic Aneurysms: A Population-Based Study

Context.— Managing thoracic aortic aneurysms identified incidentally by increased use of computed tomography, echocardiography, and magnetic resonance imaging is problematic, especially in the elderly. Objective.— To ascertain whether the previously reported poor prognosis for individuals with thoracic aortic aneurysms has changed with better medical therapies and improved surgical techniques that can now be applied to aneurysm management. Design.— Population-based cohort study. Setting and Patients.— All 133 patients with the diagnosis of degenerative thoracic aortic aneurysms among Olmsted County, Minnesota, residents between 1980 and 1994 compared with a previously reported cohort of similar patients between 1951 and 1980. Main Outcome Measures.— The primary clinical end points were incidence, cumulative rupture risk, rupture risk as a function of aneurysm size, and survival. Results.— In contrast to abdominal aortic aneurysms, for which men are affected predominately, 51% of thoracic aortic aneurysms were identified in women who were considerably older at recognition than men (mean age, 75.9 vs 62.8 years, respectively; P=.01). The overall incidence rate of 10.4 per 100,000 person-years (95% confidence interval [CI], 8.6-12.2) between 1980 and 1994 was more than 3-fold higher than the rate from 1951 to 1980. The cumulative risk of rupture was 20% after 5 years. Seventy-nine percent of ruptures occurred in women (P=.01). The 5-year risk of rupture as a function of aneurysm size at recognition was 0% for aneurysms less than 4 cm in diameter, 16% (95% CI, 4%-28%) for those 4 to 5.9 cm, and 31% (95% CI, 5%-56%) for aneurysms 6 cm or more. Overall 5-year survival improved to 56% (95% CI, 48%-66%) between 1980 and 1994 compared with only 19% between 1951 and 1980 (P<.01). Conclusions.— In this population, elderly women represent an increasing portion of all patients with clinically recognized thoracic aortic aneurysms and constitute the majority of patients whose aneurysm eventually ruptures. Overall survival for thoracic aortic aneurysms has improved significantly in the past 15 years.      

Therapies directed against epidermal growth factor receptor in aerodigestive carcinomas

Context  Malignancies arising from the aerodigestive epithelium, including lung, head and neck, and esophageal carcinomas, are the leading causes of cancer-related mortality worldwide. Given the biological importance of epidermal growth factor receptor (EGFR) in cancer development and progression, EGFR inhibitors have emerged as promising novel therapies. Objectives  To summarize the current status of EGFR inhibitors in aerodigestive carcinomas (ADCs), highlight ongoing research designed to optimize their therapeutic effectiveness, and consider the future role of these agents. Evidence Acquisition  Systematic MEDLINE search of English-language literature (1966-April 2007) performed using the terms EGFR, EGFR inhibitors, monoclonal antibodies, tyrosine kinase inhibitors, lung cancer, head and neck cancer, esophageal cancer, and EGFR predictive factors. Quality assessment of selected studies included clinical pertinence, with an emphasis on controlled study design, publication in peer-reviewed journals, adequate number of enrolled patients, objectivity of measurements, and techniques used to minimize bias. Evidence Synthesis  The role of EGFR in ADC pathogenesis has been extensively studied, and multiple EGFR inhibition strategies are under evaluation. Erlotinib, an EGFR tyrosine kinase inhibitor used as a single agent, and cetuximab, an anti-EGFR monoclonal antibody used in combination with radiation, have conferred survival benefit in 1 trial of patients with advanced non–small cell lung cancer (median survival, 6.7 vs 4.7 months; hazard ratio, 0.70; 95% confidence interval, 0.58-0.87; P < .001) and in 1 trial of patients with locally advanced head and neck squamous cell carcinoma (median survival, 49 vs 29.3 months; hazard ratio, 0.74; 95% confidence interval, 0.57-0.97; P = .03), respectively. However, other trials have not shown these degrees of improvement. EGFR inhibitors toxicities include rash, diarrhea, and hypomagnesemia. Somatic mutations and other molecular tumoral characteristics offer opportunities for treatment individualization and optimal patient selection for anti-EGFR therapy. Conclusions  EGFR is a promising therapeutic target in ADC. Further translational research is needed to optimize ways of inhibiting EGFR using single-agent or combination regimens and to identify patients who benefit the most from these therapies.      

Effects of conjugated equine estrogens on breast cancer and mammography screening in postmenopausal women with hysterectomy

Context  The Women's Health Initiative Estrogen-Aone trial comparing conjugated equine estrogens (CEE) with placebo was stopped early because of an increased stroke incidence and no reduction in risk of coronary heart disease. Preliminary results suggesting possible reduction in breast cancers warranted more detailed analysis. Objective  To determine the effects of CEE on breast cancers and mammographic findings. Design, Setting, and Participants  Following breast cancer risk assessment, 10 739 postmenopausal women aged 50 to 79 years with prior hysterectomy were randomized to CEE or placebo at 40 US clinical centers from 1993 through 1998. Mammography screenings and clinical breast examinations were performed at baseline and annually. All breast cancers diagnosed through February 29, 2004, are included. Intervention  A dose of 0.625 mg/d of CEE or an identical-appearing placebo. Main Outcome Measures  Breast cancer incidence, tumor characteristics, and mammogram findings. Results  After a mean (SD) follow-up of 7.1 (1.6) years, the invasive breast cancer hazard ratio (HR) for women assigned to CEE vs placebo was 0.80 (95% confidence interval [CI], 0.62-1.04; P = .09) with annualized rates of 0.28% (104 cases in the CEE group) and 0.34% (133 cases in the placebo group). In exploratory analyses, ductal carcinomas (HR, 0.71; 95% CI, 0.52-0.99) were reduced in the CEE group vs placebo group; however, the test for interaction by tumor type was not significant (P = .054). At 1 year, 9.2% of women in the CEE group had mammograms with abnormalities requiring follow-up vs 5.5% in the placebo group (P<.001), a pattern that continued through the trial to reach a cumulative percentage of 36.2% vs 28.1%, respectively (P<.001); however, this difference was primarily in assessments requiring short interval follow-up. Conclusions  Treatment with CEE alone for 7.1 years does not increase breast cancer incidence in postmenopausal women with prior hysterectomy. However, treatment with CEE increases the frequency of mammography screening requiring short interval follow-up. Initiation of CEE should be based on consideration of the individual woman's potential risks and benefits. Trial Registration  clinicaltrials.gov Identifier: NCT00000611      

Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation

Context  Women with BRCA1 or BRCA2 mutation are often advised to undergo preventive oophorectomy. The effectiveness of this intervention has not been prospectively evaluated in a large cohort. Objectives  To estimate the incidence of ovarian, fallopian tube, and primary peritoneal cancer in women who carry a deleterious mutation in BRCA1 or BRCA2. To estimate the reduction in risk of these cancers associated with a bilateral prophylactic salpingo-oophorectomy. Design, Setting, and Participants  Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry between 1992 and 2003. A total of 1828 carriers at 1 of 32 centers in Canada, the United States, Europe, and Israel completed questionnaires at baseline and follow-up. Participants were observed from the date of study entry until: diagnosis of ovarian, fallopian tube, or peritoneal cancer; death; or the date of the most recent follow-up. Intervention  Participants were divided into women who had undergone bilateral prophylactic oophorectomy and those who had not. Main Outcome Measure  The incidence of ovarian, peritoneal, and fallopian tube cancer was determined by survival analysis. The risk reduction associated with prophylactic salpingo-oophorectomy was evaluated by a time-dependent survival analysis, adjusting for covariates. Results  After a mean follow-up of 3.5 years, 50 incident ovarian, fallopian tube, and peritoneal cancer cases were reported in the cohort. Of the 1828 women, 555 (30%) underwent a bilateral prophylactic salpingo-oophorectomy prior to study entry, 490 (27%) underwent the procedure after entering the study, and 783 (43%) did not undergo the procedure. There were 32 incident cancers diagnosed in women with intact ovaries (1015/100 000 per year). Eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy (217/100 000 per year). The estimated cumulative incidence of peritoneal cancer is 4.3% at 20 years after oophorectomy. The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07-0.58; P = .003). Conclusion  Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.      

Sex-Based Analysis of Outcome in Patients With Acute Myocardial Infarction Treated Predominantly With Percutaneous Coronary Intervention

Context  A higher mortality risk for women with acute myocardial infarction (AMI) is a common finding in studies that compare the postinfarction outcome of women vs men. It is not clear, however, whether sex is an independent predictor of death among patients systematically treated with aggressive reperfusion and medical strategies. Objective  To assess the impact of patient's sex on outcome in a consecutive series of patients with AMI treated with a reperfusion strategy largely based on percutaneous coronary interventions. Design, Setting, and Patients  Inception cohort of 1937 patients (502 women and 1435 men) who were admitted with a diagnosis of AMI to a tertiary referral institution between January 1995 and December 2000. Main Outcome Measures  Mortality at 1 year after AMI. Results  Compared with men, women were older (70 vs 61 years; P<.001) and had known diabetes or hypertension more often. Both men and women received essentially identical therapy with the majority of patients (86%) receiving reperfusion therapy via percutaneous coronary interventions. There were no significant differences in 1-year Kaplan-Meier death rates with 13.8% (68 cases) among women and 12.9% (184 cases) among men (unadjusted hazard ratio, 1.06; 95% confidence interval, 0.80-1.39; P = .70). After age adjustment, women had a lower risk of death (hazard ratio, 0.65; 95% confidence interval, 0.49-0.87; P = .004). Conclusion  Despite their more advanced age and greater prevalence of diabetes or hypertension, women with AMI who were treated with a reperfusion strategy largely based on percutaneous coronary interventions show a similar outcome as men.      

Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial

Context  Basic research and observational evidence as well as results from trials of colon polyp recurrence suggest a role for aspirin in the chemoprevention of cancer. Objective  To examine the effect of aspirin on the risk of cancer among healthy women. Design, Setting, and Participants  In the Women’s Health Study, a randomized 2 x 2 factorial trial of aspirin and vitamin E conducted between September 1992 and March 2004, 39 876 US women aged at least 45 years and initially without previous history of cancer, cardiovascular disease, or other major chronic illness were randomly assigned to receive either aspirin or aspirin placebo and followed up for an average of 10.1 years. Intervention  A dose of 100 mg of aspirin (n=19 934) or aspirin placebo (n=19 942) administered every other day. Main Outcome Measures  Confirmed newly diagnosed invasive cancer at any site, except for nonmelanoma skin cancer. Incidence of breast, colorectal, and lung cancer were secondary end points. Results  No effect of aspirin was observed on total cancer (n = 2865; relative risk [RR], 1.01; 95% confidence interval [CI], 0.94-1.08; P = .87), breast cancer (n = 1230; RR, 0.98; 95% CI, 0.87-1.09; P = .68), colorectal cancer (n = 269; RR, 0.97; 95% CI, 0.77-1.24; P = .83), or cancer of any other site, with the exception of lung cancer for which there was a trend toward reduction in risk (n = 205; RR, 0.78; 95% CI, 0.59-1.03; P = .08). There was also no reduction in cancer mortality either overall (n = 583; RR, 0.95; 95% CI, 0.81-1.11; P = .51) or by site, except for lung cancer mortality (n = 140; RR, 0.70; 95% CI, 0.50-0.99; P = .04). No evidence of differential effects of aspirin by follow-up time or interaction with vitamin E was found. Conclusions  Results from this large-scale, long-term trial suggest that alternate day use of low-dose aspirin (100 mg) for an average 10 years of treatment does not lower risk of total, breast, colorectal, or other site-specific cancers. A protective effect on lung cancer or a benefit of higher doses of aspirin cannot be ruled out.      

Transition of extremely low-birth-weight infants from adolescence to young adulthood: comparison with normal birth-weight controls

Context  Traditionally, educational attainment, getting a job, living independently, getting married, and parenthood have been considered as markers of successful transition to adulthood. Objective  To describe and compare the achievement and the age at attainment of the above markers between extremely low-birth-weight (ELBW) and normal birth-weight (NBW) young adults. Design, Setting, and Participants  A prospective, longitudinal, population-based study in central-west Ontario, Canada, of 166 ELBW participants who weighed 501 to 1000 g at birth (1977-1982) and 145 sociodemographically comparable NBW participants assessed at young adulthood (22-25 years). Interviewers masked to participant status administered validated questionnaires via face-to-face interviews between January 1, 2002, and April 30, 2004. Main Outcome Measures  Markers of successful transition to adulthood, including educational attainment, student and/or worker role, independent living, getting married, and parenthood. Results  At young adulthood, 149 (90%) of 166 ELBW participants and 133 (92%) of 145 NBW participants completed the assessments at mean (SD) age of 23.3 (1.2) years and 23.6 (1.1) years, respectively. We included participants with neurosensory impairments (ELBW vs NBW: 40 [27%] vs 3 [2%]) and 7 proxy respondents. The proportion who graduated from high school was similar (82% vs 87%, P = .21). Overall, no statistically significant differences were observed in the education achieved to date. A substantial proportion of both groups were still pursuing postsecondary education (47 [32%] vs 44 [33%]). No significant differences were observed in employment/school status; 71 (48%) ELBW vs 76 (57%) NBW young adults were permanently employed (P = .09). In a subanalysis, a higher proportion of ELBW young adults were neither employed nor in school (39 [26%] vs 20 [15%], P = .02 by Holm's correction); these differences did not persist when participants with disabilities were excluded. No significant differences were found in the proportion living independently (63 [42%] vs 70 [53%], P = .19), married/cohabitating (34 [23%] vs 33 [25%], P = .69), or who were parents (16 [11%] vs 19 [14%], P = .36). The age at attainment of the above markers was similar for both cohorts. Conclusion  Our study results indicate that a significant majority of former ELBW infants have overcome their earlier difficulties to become functional young adults.      

Obesity-related plasma hemodilution and PSA concentration among men with prostate cancer

Context  Recent studies have suggested that obese men have lower serum prostate-specific antigen (PSA) concentrations than nonobese men. Because men with higher body mass index (BMI) have greater circulating plasma volumes, lower PSA concentrations among obese men may be due to hemodilution. Objective  To determine the association between hemodilution and PSA concentration in obese men with prostate cancer. Design, Setting, and Participants  Retrospective study of men who underwent radical prostatectomy for prostate adenocarcinoma from 1988 to 2006, using data from the databases of the Shared Equal Access Regional Cancer Hospital (n = 1373), Duke Prostate Center (n = 1974), and Johns Hopkins Hospital (n = 10 287). Multivariate linear regression models adjusting for clinicopathological characteristics were used to analyze the main outcome measures. Main Outcome Measures  Associations between BMI and mean adjusted PSA concentrations, mean plasma volume, and mean adjusted PSA mass (total circulating PSA protein, calculated as PSA concentration multiplied by plasma volume), assessed by determining P values for trend. Results  After controlling for clinicopathological characteristics, higher BMI was significantly associated with higher plasma volume (P < .001 for trend) and lower PSA concentrations (P  .02 for trend) in all cohorts. In 2 of the 3 cohorts, PSA mass did not change significantly with increasing BMI. In the third cohort, higher BMI was associated with increased PSA mass (P < .001 for trend), but only between BMI category less than 25 and the other categories. Conclusions  In men undergoing radical prostatectomy, higher BMI was associated with higher plasma volume; hemodilution may therefore be responsible for the lower serum PSA concentrations among obese men with prostate cancer. Prospective studies are needed to evaluate this association in screened populations.      

Duration of lactation and incidence of type 2 diabetes

Context  Lactation is associated with improved glucose and insulin homeostasis, independent of weight change. Objective  To evaluate the association between lactation history and incidence of type 2 diabetes. Design, Setting, and Participants  Prospective observational cohort study of 83 585 parous women in the Nurses’ Health Study (NHS) and retrospective observational cohort study of 73 418 parous women in the Nurses’ Health Study II (NHS II). Main Outcome Measure  Incident cases of type 2 diabetes mellitus. Results  In the NHS, 5145 cases of type 2 diabetes were diagnosed during 1 239 709 person-years of follow-up between 1986 and 2002, and in the NHS II, 1132 cases were diagnosed during 778 876 person-years of follow-up between 1989 and 2001. Among parous women, increasing duration of lactation was associated with a reduced risk of type 2 diabetes. For each additional year of lactation, women with a birth in the prior 15 years had a decrease in the risk of diabetes of 15% (95% confidence interval, 1%-27%) among NHS participants and of 14% (95% confidence interval, 7%-21%) among NHS II participants, controlling for current body mass index and other relevant risk factors for type 2 diabetes. Conclusions  Longer duration of breastfeeding was associated with reduced incidence of type 2 diabetes in 2 large US cohorts of women. Lactation may reduce risk of type 2 diabetes in young and middle-aged women by improving glucose homeostasis.      

Radiation dose-response relationships for thyroid nodules and autoimmune thyroid diseases in Hiroshima and Nagasaki atomic bomb survivors 55-58 years after radiation exposure

Context  Effects of irradiation on thyroid diseases such as thyroid nodules and autoimmune thyroid diseases have not been evaluated among people exposed to radiation more than 50 years in the past. Objective  To evaluate the prevalence of thyroid diseases and their radiation-dose responses in atomic bomb survivors. Design, Setting, and Participants  Survey study comprising 4091 cohort members (mean age, 70 [SD, 9] years; 1352 men and 2739 women) who participated in the thyroid study at the Radiation Effects Research Foundation. Thyroid examinations were conducted between March 2000 and February 2003. Main Outcome Measures  Prevalence of thyroid diseases, including thyroid nodules (malignant and benign) and autoimmune thyroid diseases, and the dose-response relationship of atomic bomb radiation in each thyroid disease. Results  Thyroid diseases were identified in 1833 (44.8%) of the total participants (436 men [32.2% of men] and 1397 women [51.0% of women]) (P<.001). In 3185 participants, excluding persons exposed in utero, not in the city at the time of the atomic bombings, or with unknown radiation dose, the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts was 14.6%, 2.2%, 4.9%, and 7.7%, respectively. The prevalence of positive thyroid antibodies, antithyroid antibody–positive hypothyroidism, and Graves disease was 28.2%, 3.2%, and 1.2%, respectively. A significant linear dose-response relationship was observed for the prevalence of all solid nodules, malignant tumors, benign nodules, and cysts (P<.001). We estimate that about 28% of all solid nodules, 37% of malignant tumors, 31% of benign nodules, and 25% of cysts are associated with radiation exposure at a mean and median thyroid radiation dose of 0.449 Sv and 0.087 Sv, respectively. No significant dose-response relationship was observed for positive antithyroid antibodies (P = .20), antithyroid antibody–positive hypothyroidism (P = .92), or Graves disease (P = .10). Conclusions  A significant linear radiation dose response for thyroid nodules, including malignant tumors and benign nodules, exists in atomic bomb survivors. However, there is no significant dose response for autoimmune thyroid diseases.      

Prevalence of marijuana use disorders in the United States: 1991-1992 and 2001-2002

Context  Among illicit substance use disorders, marijuana use disorders are the most prevalent in the population. Yet, information about the prevalence of current Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) marijuana use disorders and how prevalence has changed is lacking. Objective  To examine changes in the prevalence of marijuana use, abuse, and dependence in the United States between 1991-1992 and 2001-2002. Design, Setting, and Participants  Face-to-face interviews were conducted in 2 large national surveys conducted 10 years apart: the 1991-1992 National Longitudinal Alcohol Epidemiologic Survey ([NLAES] n = 42 862) and the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions ([NESARC] n = 43 093). Main Outcome Measures  Rates of past year marijuana use, abuse, and dependence. Results  Among the adult US population, the prevalence of marijuana use remained stable at about 4.0% over the past decade. In contrast, the prevalence of DSM-IV marijuana abuse or dependence significantly (P = .01) increased between 1991-1992 (1.2%) and 2001-2002 (1.5%), with the greatest increases observed among young black men and women (P<.001) and young Hispanic men (P = .006). Further, marijuana use disorders among marijuana users significantly increased (P = .002) in the absence of increased frequency and quantity of marijuana use, suggesting that the concomitant increase in potency of delta-9-tetrahydrocannabinol (⁹-THC) may have contributed to the rising rates. Conclusions  Despite the stability in the overall prevalence of marijuana use, more adults in the United States had a marijuana use disorder in 2001-2002 than in 1991-1992. Increases in the prevalence of marijuana use disorders were most notable among young black men and women and young Hispanic men. Although rates of marijuana abuse and dependence did not increase among young white men and women, their rates have remained high. The results of this study underscore the need to develop and implement new prevention and intervention programs targeted at youth, particularly minority youth.