Andrea Discacciati

Body mass index and incidence of localized and advanced prostate cancer—a dose–response meta-analysis of prospective studies

BACKGROUND The relationship between obesity and risk of prostate cancer (PCa) is unclear; however, etiologic heterogeneity by subtype of PCa (localized, advanced) related to obesity was suggested. Therefore, we conducted a dose-response meta-analysis of prospective studies to assess the association between body mass index (BMI) and risk of localized and advanced PCa. MATERIALS AND METHODS Relevant prospective studies were identified by a search of Medline and Embase databases to 03 October 2011. Twelve studies on localized PCa (1,033,009 men, 19,130 cases) and 13 on advanced PCa (1,080,790 men, 7067 cases) were identified. We carried out a dose-response meta-analysis using random-effects model. RESULTS For localized PCa, we observed an inverse linear relationship with BMI [Ptrend<0.001, relative risk (RR): 0.94 (95% confidence interval, 95% CI, 0.91-0.97) for every 5 kg/m2 increase]; there was no evidence of heterogeneity (Pheterogeneity=0.27). For advanced PCa, we observed a linear direct relationship with BMI (Ptrend=0.001, RR: 1.09 (95% CI 1.02-1.16) for every 5 kg/m2 increase); there was weak evidence of heterogeneity (Pheterogeneity=0.08). Omitting one study that contributed substantially to the heterogeneity yielded a pooled RR of 1.07 (95% CI 1.01-1.13) for every 5 kg/m2 increase (Pheterogeneity=0.26). CONCLUSIONS The quantitative summary of the accumulated evidence indicates that obesity may have a dual effect on PCa-a decreased risk for localized PCa and an increased risk for advanced PCa.

Low-Risk Diet and Lifestyle Habits in the Primary Prevention of Myocardial Infarction in Men: A Population-Based Prospective Cohort Study

BACKGROUND Adherence to a combination of healthy dietary and lifestyle practices may have an impressive impact on the primary prevention of myocardial infarction (MI). OBJECTIVES The aim of this study was to examine the benefit of combined low-risk diet and healthy lifestyle practices on the incidence of MI in men. METHODS The population-based, prospective cohort of Swedish men comprised 45- to 79-year-old men who completed a detailed questionnaire on diet and lifestyle at baseline in 1997. In total, 20,721 men with no history of cancer, cardiovascular disease, diabetes, hypertension, or high cholesterol levels were followed through 2009. Low-risk behavior included 5 factors: a healthy diet (top quintile of Recommended Food Score), moderate alcohol consumption (10 to 30 g/day), no smoking, being physically active (walking/bicycling ≥40 min/day and exercising ≥1 h/week), and having no abdominal adiposity (waist circumference <95 cm). RESULTS During 11 years of follow-up, we ascertained 1,361 incident cases of MI. The low-risk dietary choice together with moderate alcohol consumption was associated with a relative risk of 0.65 (95% confidence interval [CI]: 0.48 to 0.87) compared with men having 0 of 5 low-risk factors. Men having all 5 low-risk factors compared with those with 0 low-risk factors had a relative risk of 0.14 (95% CI: 0.04 to 0.43). This combination of healthy behaviors, present in 1% of the men, could prevent 79% (95% CI: 34% to 93%) of the MI events on the basis of the study population. CONCLUSIONS Almost 4 of 5 MIs in men may be preventable with a combined low-risk behavior.

Coffee Consumption and Mortality From All Causes, Cardiovascular Disease, and Cancer: A Dose-Response Meta-Analysis

Several studies have analyzed the relationship between coffee consumption and mortality, but the shape of the association remains unclear. We conducted a dose-response meta-analysis of prospective studies to examine the dose-response associations between coffee consumption and mortality from all causes, cardiovascular disease (CVD), and all cancers. Pertinent studies, published between 1966 and 2013, were identified by searching PubMed and by reviewing the reference lists of the selected articles. Prospective studies in which investigators reported relative risks of mortality from all causes, CVD, and all cancers for 3 or more categories of coffee consumption were eligible. Results from individual studies were pooled using a random-effects model. Twenty-one prospective studies, with 121,915 deaths and 997,464 participants, met the inclusion criteria. There was strong evidence of nonlinear associations between coffee consumption and mortality for all causes and CVD (P for nonlinearity < 0.001). The largest risk reductions were observed for 4 cups/day for all-cause mortality (16%, 95% confidence interval: 13, 18) and 3 cups/day for CVD mortality (21%, 95% confidence interval: 16, 26). Coffee consumption was not associated with cancer mortality. Findings from this meta-analysis indicate that coffee consumption is inversely associated with all-cause and CVD mortality.

Cigarette smoking and risk of rheumatoid arthritis: a dose-response meta-analysis

IntroductionAlthough previous studies found that cigarette smoking is associated with risk of rheumatoid arthritis (RA), the dose-response relationship remains unclear. This meta-analysis quantitatively summarizes accumulated evidence regarding the association of lifelong exposure to cigarette smoking assessed as pack-years with the risk of RA.MethodsRelevant studies were identified by a search of MEDLINE and EMBASE from 1966 to October 2013, with no restrictions. Reference lists from retrieved articles were also reviewed. Studies that reported relative risks (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between pack-years of cigarette smoking and rheumatoid arthritis were included in a dose-response random-effects meta-regression analysis.ResultsWe included 3 prospective cohorts and 7 case-control studies in the meta-analysis. They included a total of 4,552 RA cases. There was no indication of heterogeneity (Pheterogeneity = 0.32) and publication bias did not affect the results. Compared to never smokers, the risk of developing RA increased by 26% (RR = 1.26, 95% CI 1.14 to 1.39) among those who smoked 1 to 10 pack-years and doubled among those with more than 20 pack-years (RR for 21 to 30 pack years = 1.94, 95% CI 1.65 to 2.27). The risk of RA was not increasing further for higher exposure levels (RR for >40 pack-years = 2.07, 95% CI 1.15 to 3.73). The risk of RA was statistically significantly higher among rheumatoid factor (RF)-positive RA cases (RR = 2.47, 95% CI 2.02 to 3.02) compared to RF-negative (RR = 1.58, 95% CI 1.15 to 2.18) when comparing the highest versus lowest category of pack-years for the individual studies.ConclusionsLifelong cigarette smoking was positively associated with the risk of RA even among smokers with a low lifelong exposure. The risk of RA did not further increase with an exposure higher than 20 pack-years.

Body mass index in early and middle-late adulthood and risk of localised, advanced and fatal prostate cancer: a population-based prospective study

Background:The relationships between body mass index (BMI) during early and middle-late adulthood and incidence of prostate cancer (PCa) by subtype of the disease (localised, advanced) and fatal PCa is unclear.Methods:A population-based cohort of 36 959 Swedish men aged 45–79 years was followed up from January 1998 through December 2008 for incidence of PCa (1530 localised and 554 advanced cases were diagnosed) and through December 2007 for PCa mortality (225 fatal cases).Results:From a competing-risks analysis, incidence of localised PCa was observed to be inversely associated with BMI at baseline (middle-late adulthood; rate ratio (RR) for 35 kg m–2 when compared with 22 kg m–2 was 0.69 (95% CI 0.52–0.92)), but not at age 30. For fatal PCa, BMI at baseline was associated with a nonstatistically significant increased risk (RR for every five-unit increase: 1.12 (0.88–1.43)) and BMI at age 30 with a decreased risk (RR for every five-unit increase: 0.72 (0.51–1.01)).Conclusion:Our results indicate an inverse association between obesity during middle-late, but not early adulthood, and localised PCa. They also suggest a dual association between BMI and fatal PCa – a decreased risk among men who were obese during early adulthood and an increased risk among those who were obese during middle-late adulthood.

Lifestyle and Dietary Factors in Prostate Cancer Prevention

The etiology of prostate cancer (PCa) is still largely unknown and the only well-established risk factors are those that are non-modifiable (age, race, and family history). Therefore, the identification of lifestyle and dietary factors which might prevent PCa development and progression is of paramount importance from a public health point of view. Accumulating evidence indicates that obesity may have a dual effect on PCa: an increased risk of aggressive PCa and a decreased risk of localized PCa. Both occupational and leisure time physical activity have been observed to be associated with a reduced PCa risk. Different dietary factors including coffee have been examined in several epidemiological studies, but results have been mostly inconsistent. However, these inconsistencies can be, at least partly, explained by the fact that the majority of those studies examined total PCa risk only and, in addition, they did not take into account the different genetic characteristics within the study populations. Therefore, the future epidemiological studies should focus on the analysis of PCa subtypes separately in order to examine possible etiological heterogeneity of PCa in relation to some exposures. In addition, differences in the genetic characteristics of the study participants should be taken into account to explore the possibility of gene-environment interactions.

Coffee consumption and risk of nonaggressive, aggressive and fatal prostate cancer—a dose–response meta-analysis

BACKGROUND Existing epidemiological evidence is controversial regarding the possible associations between coffee consumption and risk of prostate cancer (PCa) by aggressiveness of the disease. MATERIALS AND METHODS We conducted a random-effects dose-response meta-analysis to assess the relationships between coffee consumption and nonaggressive, aggressive and fatal PCa risk. Studies were identified by a search of Medline and Embase databases to 15 July 2013. We carried out separate analyses by grade (Gleason score: low-grade, high-grade) and stage (TNM staging system: localized, advanced) of the tumors. Nonaggressive tumors were defined as low-grade or localized, while aggressive tumors were defined as high-grade or advanced. RESULTS Eight studies (three case-control and five cohort) were included in this meta-analysis. Gleason 7 tumors were classified as high-grade in one study, while in another study, Gleason 7(4 + 3) tumors were classified as high-grade and Gleason 7(3 + 4) as low-grade. In the remaining four studies, Gleason 7 tumors were excluded from the analyses or analyzed separately. The pooled relative risk (RR) for a consumption increment of 3 cups/day was 0.97 [95% confidence interval (CI) 0.92-1.03] for low-grade PCa (n = 6), 0.97 (95% CI 0.94-0.99) for localized PCa (n = 6), 0.89 (95% CI 0.78-1.00) for high-grade PCa (n = 6), 0.95 (95% CI 0.85-1.06) for advanced PCa (n = 6) and 0.89 (95% CI 0.82-0.97) for fatal PCa (n = 4). No evidence of publication bias was observed. Heterogeneity was absent or marginal (I(2) range = 0-26%), with the only exception of the analysis on advanced PCa, where moderate heterogeneity was observed (I(2) = 60%). When restricting the analyses only to those studies that defined high-grade tumors as Gleason 8-10, the inverse association became slightly stronger [RR: 0.84 (95% CI 0.72-0.98); n = 4]. CONCLUSIONS Results from this dose-response meta-analysis suggest that coffee consumption may be inversely associated with the risk of fatal PCa. No clear evidence of an association with PCa incidence was observed.BACKGROUND Existing epidemiological evidence is controversial regarding the possible associations between coffee consumption and risk of prostate cancer (PCa) by aggressiveness of the disease. MATERIALS AND METHODS We conducted a random-effects dose-response meta-analysis to assess the relationships between coffee consumption and nonaggressive, aggressive and fatal PCa risk. Studies were identified by a search of Medline and Embase databases to 15 July 2013. We carried out separate analyses by grade (Gleason score: low-grade, high-grade) and stage (TNM staging system: localized, advanced) of the tumors. Nonaggressive tumors were defined as low-grade or localized, while aggressive tumors were defined as high-grade or advanced. RESULTS Eight studies (three case-control and five cohort) were included in this meta-analysis. Gleason 7 tumors were classified as high-grade in one study, while in another study, Gleason 7(4 + 3) tumors were classified as high-grade and Gleason 7(3 + 4) as low-grade. In the remaining four studies, Gleason 7 tumors were excluded from the analyses or analyzed separately. The pooled relative risk (RR) for a consumption increment of 3 cups/day was 0.97 [95% confidence interval (CI) 0.92-1.03] for low-grade PCa (n = 6), 0.97 (95% CI 0.94-0.99) for localized PCa (n = 6), 0.89 (95% CI 0.78-1.00) for high-grade PCa (n = 6), 0.95 (95% CI 0.85-1.06) for advanced PCa (n = 6) and 0.89 (95% CI 0.82-0.97) for fatal PCa (n = 4). No evidence of publication bias was observed. Heterogeneity was absent or marginal (I2 range = 0-26%), with the only exception of the analysis on advanced PCa, where moderate heterogeneity was observed (I2 = 60%). When restricting the analyses only to those studies that defined high-grade tumors as Gleason 8-10, the inverse association became slightly stronger [RR: 0.84 (95% CI 0.72-0.98); n = 4]. CONCLUSIONS Results from this dose-response meta-analysis suggest that coffee consumption may be inversely associated with the risk of fatal PCa. No clear evidence of an association with PCa incidence was observed.

Coffee consumption and risk of localized, advanced and fatal prostate cancer: a population-based prospective study

BACKGROUND The epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited. MATERIALS AND METHODS A population-based cohort of 44 613 Swedish men aged 45-79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI). RESULTS For localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95-0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95-1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93-1.03)]. We observed evidence of effect modification by BMI for localized PCa (Pinteraction = 0.03); the inverse association was stronger among overweight and obese men (BMI ≥ 25 kg/m2) compared with normal-weight men (BMI < 25 kg/m2). CONCLUSIONS We observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men.BACKGROUND The epidemiological evidence on possible relationships between coffee consumption and prostate cancer (PCa) risk by subtype of the disease (localized, advanced) and fatal PCa risk is limited. MATERIALS AND METHODS A population-based cohort of 44 613 Swedish men aged 45-79 years was followed up from January 1998 through December 2010 for incidence of localized (n = 2368), advanced (n = 918) and fatal (n = 515) PCa. We assessed the associations between coffee consumption and localized, advanced and fatal PCa risk using competing-risk regressions. We examined possible effect modification by body mass index (BMI). RESULTS For localized PCa, each one cup increase in daily coffee consumption was associated with a 3% reduced risk [sub-hazard ratio (SHR) = 0.97, 95% confidence interval (CI) = 0.95-0.99]. For advanced and fatal PCa, we found a non-significant inverse association; each one cup increase was associated with a 2% reduced risk of advanced [SHR (95% CI) = 0.98 (0.95-1.02)] and fatal PCa [SHR (95% CI) = 0.98 (0.93-1.03)]. We observed evidence of effect modification by BMI for localized PCa (Pinteraction = 0.03); the inverse association was stronger among overweight and obese men (BMI ≥ 25 kg/m(2)) compared with normal-weight men (BMI < 25 kg/m(2)). CONCLUSIONS We observed a clear inverse association between coffee consumption and risk of localized PCa, especially among overweight and obese men.

Using Laplace Regression to Model and Predict Percentiles of Age at Death When Age Is the Primary Time Scale

Increasingly often in epidemiologic research, associations between survival time and predictors of interest are measured by differences between distribution functions rather than hazard functions. For example, differences in percentiles of survival time, expressed in absolute time units (e.g., weeks), may complement the popular risk ratios, which are unitless measures. When analyzing time to an event of interest (e.g., death) in prospective cohort studies, the time scale can be set to start at birth or at study entry. The advantages of one time origin over the other have been thoroughly explored for the estimation of risks but not for the estimation of survival percentiles. In this paper, we analyze the use of different time scales in the estimation of survival percentiles with Laplace regression. Using this regression method, investigators can estimate percentiles of survival time over levels of an exposure of interest while adjusting for potential confounders. Our findings may help to improve modeling strategies and ease interpretation in the estimation of survival percentiles in prospective cohort studies.

B-type natriuretic peptide and risk of acute kidney injury in patients hospitalized with acute coronary syndromes*.

Objectives:To investigate whether admission B-type natriuretic peptide levels predict the development of acute kidney injury in acute coronary syndromes. Design:Prospective study. Setting:Single-center study, 13-bed intensive cardiac care unit at a University Cardiological Center. Patients:Six-hundred thirty-nine acute coronary syndromes patients undergoing emergency and urgent percutaneous coronary intervention. Interventions:None. Measurements and Main Results.We measured B-type natriuretic peptide at hospital admission in acute coronary syndromes patients (55% ST-elevation myocardial infarction and 45% non–ST-elevation myocardial infarction). Acute kidney injury was classified according to the Acute Kidney Injury Network criteria: stage 1 was defined as a serum creatinine increase greater than or equal to 0.3 mg/dL from baseline; stage 2 as a serum creatinine increase greater than two- to three-fold from baseline; stage 3 as a serum creatinine increase greater than three-fold from baseline, or greater than or equal to 4.0 mg/dL with an acute increase greater than 0.5 mg/dL, or need for renal replacement therapy. Acute kidney injury was developed in 85 patients (13%) and had a higher in-hospital mortality than patients without acute kidney injury (14% vs 1%; p < 0.001). B-type natriuretic peptide levels were higher in acute kidney injury patients than in those without acute kidney injury (264 [112–957] vs 98 [44–271] pg/mL; p < 0.001) and showed a significant gradient according to acute kidney injury severity (224 [96–660] pg/mL in stage 1 and 939 [124–1,650] pg/mL in stage 2–3 acute kidney injury; p < 0.001). The risk of developing acute kidney injury increased in parallel with B-type natriuretic peptide quartiles (5%, 9%, 15%, and 24%, respectively; p < 0.001). When B-type natriuretic peptide was evaluated, in terms of capacity to predict acute kidney injury, the area under the curve was 0.702 (95% CI, 0.642–0.762). Conclusions:In patients hospitalized with acute coronary syndromes, B-type natriuretic peptide levels measured at admission are associated with acute kidney injury as well as its severity.