AbstractObjectiveTo examine how a healthy lifestyle is related to life expectancy that is free from major chronic diseases.DesignProspective cohort study.Setting and participantsThe Nurses’ Health ...Study (1980-2014; n=73 196) and the Health Professionals Follow-Up Study (1986-2014; n=38 366).Main exposuresFive low risk lifestyle factors: never smoking, body mass index 18.5-24.9, moderate to vigorous physical activity (≥30 minutes/day), moderate alcohol intake (women: 5-15 g/day; men 5-30 g/day), and a higher diet quality score (upper 40%).Main outcomeLife expectancy free of diabetes, cardiovascular diseases, and cancer.ResultsThe life expectancy free of diabetes, cardiovascular diseases, and cancer at age 50 was 23.7 years (95% confidence interval 22.6 to 24.7) for women who adopted no low risk lifestyle factors, in contrast to 34.4 years (33.1 to 35.5) for women who adopted four or five low risk factors. At age 50, the life expectancy free of any of these chronic diseases was 23.5 (22.3 to 24.7) years among men who adopted no low risk lifestyle factors and 31.1 (29.5 to 32.5) years in men who adopted four or five low risk lifestyle factors. For current male smokers who smoked heavily (≥15 cigarettes/day) or obese men and women (body mass index ≥30), their disease-free life expectancies accounted for the lowest proportion (≤75%) of total life expectancy at age 50.ConclusionAdherence to a healthy lifestyle at mid-life is associated with a longer life expectancy free of major chronic diseases.
Mineralocorticoid receptor (MR) antagonists are the recommended medical therapy for primary aldosteronism. Whether this recommendation effectively reduces cardiometabolic risk is not well understood. ...We aimed to investigate the risk of incident cardiovascular events in patients with primary aldosteronism treated with MR antagonists compared with patients with essential hypertension.
We did a cohort study using patients from a research registry from Brigham and Women's Hospital, Massachusetts General Hospital, and their affiliated partner hospitals. We identified patients with primary aldosteronism using International Classification of Disease, 9th and 10th Revision codes, who were assessed between the years 1991-2016 and were at least 18 years of age. We excluded patients who underwent surgical adrenalectomy, had a previous cardiovascular event, were not treated with MR antagonists, or had no follow-up visits after study entry. From the same registry, we identified a population with essential hypertension that was frequency matched by decade of age at study entry. We extracted patient cohort data and collated it into a de-identified database. The primary outcome was an incident cardiovascular event, defined as a composite of incident myocardial infarction or coronary revascularisation, hospital admission with congestive heart failure, or stroke, which was assessed using adjusted Cox regression models. Secondary outcomes were the individual components of the composite cardiovascular outcome, as well as incident atrial fibrillation, incident diabetes, and death.
We identified 602 eligible patients with primary aldosteronism treated with MR antagonists and 41 853 age-matched patients with essential hypertension from the registry. The two groups of patients had comparable cardiovascular risk profiles and blood pressure throughout the study. The incidence of cardiovascular events was higher in patients with primary aldosteronism on MR antagonists than in patients with essential hypertension (56·3 95% CI 48·8-64·7 vs 26·6 26·1-27·2 events per 1000 person-years, adjusted hazard ratio 1·91 95% CI 1·63-2·25; adjusted 10-year cumulative incidence difference 14·1 95% CI 10·1-18·0 excess events per 100 people). Patients with primary aldosteronism also had higher adjusted risks for incident mortality (hazard ratio HR 1·34 95% CI 1·06-1·71), diabetes (1·26 1·01-1·57), and atrial fibrillation (1·93 1·54-2·42). Compared with essential hypertension, the excess risk for cardiovascular events and mortality was limited to patients with primary aldosteronism whose renin activity remained suppressed (<1 μg/L per h) on MR antagonists (adjusted HR 2·83 95% CI 2·11-3·80, and 1·79 1·14-2·80, respectively) whereas patients who were treated with higher MR antagonist doses and had unsuppressed renin (≥1 μg/L per h) had no significant excess risk.
The current practice of MR antagonist therapy in primary aldosteronism is associated with significantly higher risk for incident cardiometabolic events and death, independent of blood pressure control, than for patients with essential hypertension. Titration of MR antagonist therapy to raise renin might mitigate this excess risk.
US National Institutes of Health.
Lifelong therapy with mineralocorticoid receptor antagonists (MRAs) or surgical adrenalectomy are the recommended treatments for primary aldosteronism (PA). Whether these treatments mitigate the risk ...for kidney disease remains unknown. We performed a retrospective cohort study of patients with PA treated with MRAs (N=400) or surgical adrenalectomy (N=120) and age- and estimated glomerular filtration rate–matched patients with essential hypertension (N=15 474) to determine risk for chronic kidney disease and longitudinal estimated glomerular filtration rate decline. Despite similar blood pressures, patients with PA treated with MRAs had a higher risk for incident chronic kidney disease compared with essential hypertension patients (adjusted hazard ratio, 1.63; 95% confidence interval, 1.33–1.99). Correspondingly, the adjusted annual decline in estimated glomerular filtration rate was greater in PA patients treated with MRAs compared with essential hypertension patients (−1.6; 95% confidence interval, −1.4 to −1.8 versus −0.9; 95% confidence interval, −0.9 to −1.0 mL/min per 1.73 m/y; P<0.001). In contrast, patients with unilateral PA treated with surgical adrenalectomy had no significant difference in risk for incident chronic kidney disease or in an annual decline in estimated glomerular filtration rate compared with essential hypertension patients. Among PA patients with diabetes mellitus treated with MRAs, there was a higher risk for incident albuminuria compared with essential hypertension (adjusted hazard ratio, 2.52; 95% confidence interval, 1.28–4.96). MRA therapy in PA is associated with higher risk for developing chronic kidney disease when compared with essential hypertension, and surgical adrenalectomy may mitigate this risk. When possible, curative surgical adrenalectomy may be superior to lifelong MRA therapy in preventing kidney disease in PA.
This trial tested the effect of adding bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, to the taxane paclitaxel for the initial treatment of metastatic breast cancer. ...As compared with paclitaxel alone, the combination increased progression-free survival but not overall survival. The results are a demonstration of the potential benefit of antiangiogenic treatment for breast cancer.
This trial tested the effect of adding bevacizumab, a monoclonal antibody against vascular endothelial growth factor A, to paclitaxel for the initial treatment of metastatic breast cancer. As compared with paclitaxel alone, the combination increased progression-free survival but not overall survival.
Laboratory and clinical evidence supports the central role of angiogenesis in the progression of breast cancer.
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Multiple angiogenic factors are commonly expressed by invasive breast cancers; the 121-amino-acid isoform of vascular endothelial growth factor (VEGF) predominates.
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VEGF stimulates endothelial proliferation and migration, inhibits endothelial apoptosis, induces proteinases that remodel the extracellular matrix, increases vascular permeability and vasodilatation, and inhibits antigen-presenting dendritic cells.
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Differences in function among the various VEGF isoforms are not well defined, though VEGF-C has a predominant role in lymphangiogenesis, whereas VEGF-A is more potent in inducing vasodilatation and pathologic angiogenesis.
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Bevacizumab (Avastin, Genentech) is a . . .
In this study, smoking cessation that was accompanied by substantial weight gain was associated with an increased short-term risk of type 2 diabetes but did not mitigate the benefits of quitting ...smoking on reducing cardiovascular and all-cause mortality.
Recent studies suggest that tumor-infiltrating lymphocytes (TILs) are associated with disease-free (DFS) and overall survival (OS) in operable triple-negative breast cancer (TNBC). We seek to ...validate the prognostic impact of TILs in primary TNBCs in two adjuvant phase III trials conducted by the Eastern Cooperative Oncology Group (ECOG).
Full-face hematoxylin and eosin–stained sections of 506 tumors from ECOG trials E2197 and E1199 were evaluated for density of TILs in intraepithelial (iTILs) and stromal compartments (sTILs). Patient cases of TNBC from E2197 and E1199 were randomly selected based on availability of sections. For the primary end point of DFS, association with TIL scores was determined by fitting proportional hazards models stratified on study. Secondary end points were OS and distant recurrence–free interval (DRFI). Reporting recommendations for tumor marker prognostic studies criteria were followed, and all analyses were prespecified.
The majority of 481 evaluable cancers had TILs (sTILs, 80%; iTILs, 15%). With a median follow-up of 10.6 years, higher sTIL scores were associated with better prognosis; for every 10% increase in sTILs, a 14% reduction of risk of recurrence or death (P = .02), 18% reduction of risk of distant recurrence (P = .04), and 19% reduction of risk of death (P = .01) were observed. Multivariable analysis confirmed sTILs to be an independent prognostic marker of DFS, DRFI, and OS.
In two national randomized clinical trials using contemporary adjuvant chemotherapy, we confirm that stromal lymphocytic infiltration constitutes a robust prognostic factor in TNBCs. Studies assessing outcomes and therapeutic efficacies should consider stratification for this parameter.
The molecular features of colorectal tumors differ with their anatomic location. Colorectal tumors are usually classified as proximal or distal. We collected data from 3 cohorts to identify ...demographic, clinical, anthropometric, lifestyle, and dietary risk factors for colorectal cancer (CRC) at 7 anatomic subsites. We examined whether the associations differ among refined subsites and whether there are trends in associations from cecum to rectum.
We collected data from the Nurses’ Health Study, Nurses’ Health Study 2, and Health Professionals Follow-up Study (45,351 men and 178,016 women, followed for a median 23 years) on 24 risk factors in relation to risk of cancer in cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectosigmoid junction, and rectum. Hazard ratios were estimated using Cox proportional hazards regression. We tested for linear and nonlinear trends in associations with CRC among subsites and within proximal colon, distal colon, and rectum.
We documented 3058 cases of CRC (474 in cecum, 633 in ascending colon, 250 in transverse colon, 221 in descending colon, 750 in sigmoid colon, 202 in rectosigmoid junction, and 528 in rectum). The positive associations with cancer risk decreased, from cecum to rectum, for age and family history of CRC. In contrast, the inverse associations with cancer risk increased, from cecum to rectum, for endoscopic screening and intake of whole grains, cereal fiber, and processed red meat. There was a significant nonlinear trend in the association between CRC and female sex, with hazard ratios ranging from 1.73 for ascending colon cancer to 0.54 for sigmoid colon cancer. For proximal colon cancers, the association with alcohol consumption and smoking before age 30 years increased from the cecum to transverse colon. For distal colon cancers, the positive association with waist circumference in men was greater for descending vs sigmoid colon cancer.
In an analysis of 3058 cases of CRC, we found that risk factor profiles differed for cancers along the colorectum. Proximal vs distal classifications are not sufficient to encompass the regional variations in colorectal tumor features and risk factors.
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The Healthy Eating Index-2005 (HEI-2005) measures adherence to the 2005 Dietary Guidelines for Americans, but the association between the HEI-2005 and risk of chronic disease is not known. The ...Alternative Healthy Eating Index (AHEI), which is based on foods and nutrients predictive of chronic disease risk, was associated inversely with chronic disease risk previously. We updated the AHEI, including additional dietary factors involved in the development of chronic disease, and assessed the associations between the AHEI-2010 and the HEI-2005 and risk of major chronic disease prospectively among 71,495 women from the Nurses' Health Study and 41,029 men from the Health Professionals Follow-Up Study who were free of chronic disease at baseline. During ≥24 y of follow-up, we documented 26,759 and 15,558 incident chronic diseases (cardiovascular disease, diabetes, cancer, or nontrauma death) among women and men, respectively. The RR (95% CI) of chronic disease comparing the highest with the lowest quintile was 0.84 (0.81, 0.87) for the HEI-2005 and 0.81 (0.77, 0.85) for the AHEI-2010. The AHEI-2010 and HEI-2005 were most strongly associated with coronary heart disease (CHD) and diabetes, and for both outcomes the AHEI-2010 was more strongly associated with risk than the HEI-2005 (P-difference = 0.002 and <0.001, respectively). The 2 indices were similarly associated with risk of stroke and cancer. These findings suggest that closer adherence to the 2005 Dietary Guidelines may lower risk of major chronic disease. However, the AHEI-2010, which included additional dietary information, was more strongly associated with chronic disease risk, particularly CHD and diabetes.
The relation between sodium intake and cardiovascular disease is controversial. This study used individual-participant data from six prospective cohorts of healthy adults. Higher sodium and lower ...potassium intakes, estimated from multiple 24-hour urine samples, were associated in a dose-dependent manner with a higher cardiovascular risk.
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