Risk Advancement Periods Research Articles

Overall and age-specific risk advancement periods of colorectal cancer for men vs women: Implications for gender-sensitive screening offers?

Colorectal cancer (CRC) incidence and mortality are higher among men than among women. We aimed to estimate overall and age-specific risk advancement periods (RAPs) for men compared to women, which quantify how many years earlier comparable levels of risk are reached by men. RAPs were derived by Cox regression models among 331 224 participants aged 40 to 69 at baseline of the UK Biobank with no previous diagnosis of CRC and no previous CRC screening examination who were followed with respect to CRC incidence for up to 13 years. Men were at substantially higher risk of CRC than women in age groups 50 to 59 and 60 to 69, with RAPs (95% confidence intervals) as high as 8.7 (4.5-13.0) and 6.2 (4.5-7.9), respectively. These RAPs were higher than those for family history of CRC in these age groups. By contrast, no significant sex difference but a major impact of family history was seen in age group 40 to 49 (P-value for interaction between sex and age = .00079). The observed patterns suggest that consideration of gender-specific starting ages of screening might be warranted in countries in which screening offers start at ages above 50 years.

Association of ideal cardiovascular health with cardiovascular events and risk advancement periods in a Mediterranean population-based cohort

BackgroundThe American Heart Association recommends Life’s Simple 7 as ideal cardiovascular health (ICVH) to reduce cardiovascular risk. Rate advancement period (RAP), a useful tool to quantify and communicate exposure impact on risks, may enhance communication about the benefits of achieving ICVH. We aimed to examine whether greater adherence to ICVH metrics was associated with reduced incidence of cardiovascular risk in a population-based cohort and estimate its impact on the timing of occurrence using RAP.MethodsProspective analyses of 3826 participants, initially free from cardiovascular disease at baseline, enrolled in the Vascular Risk in Navarra Study (RIVANA), a Mediterranean population-based cohort of Spanish adults. ICVH metrics were defined using participants’ baseline information as follows: never-smoker or quitting > 12 months ago, body mass index < 25 kg/m2, ≥ 150 min/week of moderate physical activity or equivalent, healthy dietary pattern (≥ 9 points on a validated 14-item Mediterranean diet adherence screener), untreated cholesterol < 200 mg/dL, untreated blood pressure < 120/80 mmHg, and untreated fasting blood glucose < 100 mg/dL. Participants were assigned 1 point for each achieved metric and were grouped according to their number of accumulated metrics in ≤ 2, 3, 4, and ≥ 5. The primary endpoint was major cardiovascular events (composite of myocardial infarction, stroke, or death from cardiovascular causes). Cox proportional hazard ratios (HRs) and RAPs with their corresponding 95% confidence intervals (95% CI) adjusted for potential confounders were calculated.ResultsDuring a median follow-up of 12.8 years (interquartile range 12.3–13.1), a total of 194 primary endpoints were identified. Compared to participants with ≤ 2 ideal metrics, HR (95% CI) for major cardiovascular events among participants meeting ≥ 5 metrics was 0.32 (0.17–0.60) with RAP (95% CI) of − 14.4 years (− 22.9, − 5.9).ConclusionsGreater adherence to ICVH metrics was associated with lower cardiovascular risk among Spanish adults of the RIVANA cohort. Adherence to ideal metrics may substantially delay cardiovascular risk.

Healthy lifestyle and the risk of conventional adenomas and serrated polyps: Findings from a large colonoscopy screening population.

Evidence on the link between healthy lifestyle and colorectal cancer (CRC) precursors is limited. Our study aimed to examine and compare the associations of healthy lifestyle with CRC precursors in adenoma (AD)-carcinoma and serrated pathways. A total of 24 480 participants including 6309 ADs, 1343 serrated polyps (SPs), and 16 828 polyp-free controls were included. A healthy lifestyle score (HLS) was constructed based on five lifestyle factors including cigarette smoking, alcohol drinking, physical activity, diet and body weight, and categorized into least, slightly, moderately and most healthy. Multivariable logistic regressions were used to estimate odds ratio (OR) and 95% confidence interval (CI). Inverse dose-response associations between the HLS and risk of ADs were observed (OR per 1 score increment for ADs: 0.82 [95% CI 0.79-0.84]; for SPs: 0.73 [95% CI 0.69-0.78]), and the association with SPs was more evident than with ADs (OR 0.90, 95% CI 0.85-0.96). Compared to participants with the least healthy lifestyle, those with the most healthy lifestyle had 47% lower risk of ADs (OR 0.53, 95% CI 0.47-0.59) and 70% lower risk of SPs (OR 0.30, 95% CI 0.23-0.39), respectively. These inverse associations were consistent across lesion stage and anatomic subsite and not modified by any stratification factors. The risk advancement periods for the most vs the least healthy lifestyle were -9.49 years for ADs and -20.69 years for SPs. Our findings help confirm the preventive role of healthy lifestyle in colorectal carcinogenesis.

Genetic Risk Score Is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population

The presence of specific single nucleotide polymorphisms (SNPs) can be used to calculate an individual's risk for colorectal cancer (CRC), called a genetic risk score (GRS). We investigated whether GRS can identify individuals with clinically relevant neoplasms in a screening colonoscopy population. We derived a GRS based on 48 SNPs associated with CRC, identified in a comprehensive literature search. We obtained genetic data from 1043 participants (50-79 years old) in a screening colonoscopy study in Germany, recruited from 2005 through 2013 (294 with advanced neoplasms, 249 with non-advanced adenoma (NAAs), and 500 without neoplasms). Each participant was assigned a GRS by aggregating their risk alleles (0, 1, or 2). Risk of advanced neoplasms and NAA according to GRS was calculated by multiple logistic regression. Risk advancement periods were calculated. We replicated our findings using data from a subset of the Tennessee Colorectal Polyp Study. An increased GRS was associated with higher prevalence of advanced neoplasms, but not NAAs. Participants in the middle and upper tertiles of GRS had a 2.2-fold and 2.7-fold increase in risk, respectively, of advanced neoplasms compared to those in the lower tertile. Adjusted odds ratios (ORs) were 1.09 (95% confidence interval [CI], 0.76-1.57) for NAA in the middle tertile and 1.05 (95% CI, 0.70-1.55) for NAA in the upper tertile. The ORs were largest for proximal advanced neoplasms for participants in the middle tertile (OR, 3.55; 95% CI 1.85-6.82) and the upper tertile (OR, 3.61; 95% CI 1.84-7.10). The risk advancement period for medium vs low GRS was 13.4 years (95% CI 4.8-22.0) and for high vs low GRS was 17.5 years (95% CI, 7.8-27.3). In a genetic analysis of participants in a CRC screening study in Germany, an increased GRS (based on CRC-associated SNPs) was associated with increased prevalence of advanced neoplasms. These findings might be used in defining risk-adapted screening ages.

Adherence to the WCRF/AICR Dietary Recommendations for Cancer Prevention and Risk of Cancer in Elderly from Europe and the United States: A Meta-Analysis within the CHANCES Project.

It is unknown whether dietary recommendations for cancer prevention are applicable to the elderly. We analyzed WCRF/AICR recommendations in cohorts of European and U.S. adults ages 60 years and above. Individual participant data meta-analysis included 362,114 participants (43% women), from seven prospective cohort studies, free from cancer at enrollment. The WCRF/AICR diet score was based on: (i) energy-dense foods and sugary drinks, (ii) plant foods, (iii) red and processed meat, and (iv) alcoholic drinks. Cox proportional hazards regression was used to examine the association between the diet score and cancer risks. Adjusted, cohort-specific HRs were pooled using random-effects meta-analysis. Risk advancement periods (RAP) were calculated to quantify the time period by which the risk of cancer was postponed among those adhering to the recommendations. After a median follow-up of 11 to 15 years across cohorts, 70,877 cancer cases were identified. Each one-point increase in the WCRF/AICR diet score [range, 0 (no) to 4 (complete adherence)] was significantly associated with a lower risk of total cancer [HR, 0.94; 95% confidence interval (CI), 0.92-0.97], cancers of the colorectum (HR, 0.84; 95% CI, 0.80-0.89) and prostate (HR, 0.94; 95% CI, 0.92-0.97), but not breast or lung. Adherence to an additional component of the WCRF/AICR diet score significantly postponed the incidence of cancer at any site by 1.6 years (RAP, -1.6; 95% CI, -4.09 to -2.16). Adherence to WCRF/AICR dietary recommendations is associated with lower risk of cancer among older adults. Dietary recommendations for cancer prevention are applicable to the elderly. Cancer Epidemiol Biomarkers Prev; 26(1); 136-44. ©2016 AACR.

Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium

Objective To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report...

Smoking and potentially preventable hospitalisation: The benefit of smoking cessation in older ages

AimsReducing preventable hospitalisation is a priority for health systems worldwide. This study sought to quantify the contribution of smoking to preventable hospitalisation in older adults and the potential benefits of smoking cessation. MethodsSelf-reported smoking data for 267,010 Australian men and women aged 45+ years linked with administrative hospital data were analysed using Cox's models to estimate the effects on risk of hospitalisation for congestive heart failure (CHF), diabetes complications, chronic obstructive pulmonary disease (COPD) and angina. The impacts of smoking and quitting smoking were also quantified using risk advancement periods (RAP). ResultsThe cohort included 7% current smokers, 36% former smokers and 57% never smokers. During an average follow-up of 2.7 years, 4% of participants had at least one hospitalisation for any of the study conditions (0.8% for CHF, 1.7% for diabetes complications, 0.8% for COPD and 1.4% for angina). Compared to never smokers, the adjusted hazard ratio for hospitalisation for any of the conditions for current smokers was 1.89 (95% CI 1.75–2.03), and the RAP was 3.8 years. There were strong dose-response relationships between smoking duration, smoking intensity and cumulative smoking dose on hospitalisation risk. The excess risk of hospitalisation and RAP for COPD was reduced within 5 years of smoking cessation across all age groups, but risk reduction for other conditions was only observed after 15 years. ConclusionSmoking is associated with increased risk of preventable hospitalisation for chronic conditions in older adults and smoking cessation, even at older ages, reduces this risk.

Impact of smoking and quitting on cardiovascular outcomes and risk advancement periods among older adults

Smoking is an established risk factor for cardiovascular events, such as myocardial infarction, stroke and cardiovascular death. However, most pertinent studies primarily relied on middle aged adults. We aimed to provide empirical evidence on the association of smoking with cardiovascular events and the benefits of smoking cessation in people aged 50years or older. In a German population-based cohort study detailed information on lifetime smoking history was obtained from 8,807 individuals aged 50-74years, without previous myocardial infarction (MI) or stroke. Cox proportional hazards regression was applied to estimate the impact of smoking on MI, stroke and cardiovascular death (CVD) as well as on the combined outcome of major cardiovascular events (MI, stroke or CVD). In addition, the impact of smoking and the benefits of smoking cessation were quantified by risk advancement periods (RAP). The cohort included 17.2% current smokers, 31.7% former smokers and 51.1% never smokers. During a mean follow-up of 9.1years, 261 participants experienced a first MI, 456 had a primary stroke and 274 died of cardiovascular reasons. Compared to never smokers, adjusted hazard ratios (95% confidence intervals) of current smokers were 2.25 (1.62-3.12), 2.12 (1.65-2.73) and 2.45 (1.76-3.42) and RAPs were 19.3, 9.8 and 8.4years for MI, stroke and CVD, respectively. Strong dose-response relationships were seen with both current and life-time amount of smoking. Most of the excess risk and risk advancement disappeared within 5years after smoking cessation. Smoking is a strong risk factor for cardiovascular events even at older age. Smoking cessation is highly and rapidly beneficial also at advanced age.

Impact of occupational and lifestyle factors on the occurrence of knee osteoarthritis – calculation of risk and rate advancement periods in a case-control study

Impact of occupational and lifestyle factors on the occurrence of knee osteoarthritis – calculation of risk and rate advancement periods in a case-control study

Sex, Age, and Birth Cohort Effects in Colorectal Neoplasms

Prevalence of advanced colorectal neoplasms increases with age and is higher among men than women. Cross-sectional analyses estimated that men reach an equivalent prevalence at a much younger age than women. However, cross-sectional estimates may be confounded by birth cohort effects. To estimate age and cohort effects in advanced colorectal neoplasms and to adjust risk-advancement periods for men compared with women for birth cohort effects. Age-cohort analyses. German screening colonoscopy program, 2003 to 2007. 2 185 153 participants aged 55 to 75 years. Sex- and age-specific prevalence of colorectal cancer (CRC) and advanced neoplasms (CRC or advanced adenoma) were plotted with and without stratification by birth cohort. Risk-advancement periods with 95% CI for men compared with women were estimated from log-binomial regression models with and without cross-sectional analysis adjustment for birth cohort effects. Overall, 17 196 participants (0.8%) had CRC and 152 429 (7.0%) had any advanced neoplasm. Age-specific prevalence was higher in men than in women and in later birth cohorts. The apparent modest increase in prevalence by age in cross-sectional analysis was much steeper after birth cohort effects were controlled for. In cross-sectional analysis, risk-advancement periods (95% CI) for men compared with women were 8.4 years (CI, 7.7 to 9.0 years) and 16.1 years (CI, 15.8 to 16.5 years) for CRC and any advanced neoplasm, respectively, and 3.4 years (CI, 2.6 to 4.3 years) and 6.9 years (CI, 6.4 to 7.4 years) after controlling for birth cohort effects. Information on covariates that could explain cohort effects was lacking. In this population, strong cohort effects reduced age gradients in advanced colorectal neoplasms and inflated risk-advancement periods for men compared with women, but major risk advancement persisted, even after birth cohort effects were controlled for. None.

Quantifying delay in access to new medical treatment: an application of risk advancement period methodology.

We present a novel application of the concept of risk or rate advancement to compute the extent of delay in adoption of an effective new drug in 2 German health insurance systems. We identified individuals with migraines, age 18 to 65 years, in 371 primary care practices in Germany in 1994 (MediPlus, IMS Health database). These included 8173 persons covered under the statutory health insurance system and 503 persons covered by private health insurance. We derived risk and population risk advancement periods for sumatriptan compared with nonserotoninergic acute migraine therapy using multiplicative risk regression and generalized estimating equations, adjusted for patient, physician, and practice cofactors. For patients at the mean age of the cohort, 43 years of age, sumatriptan was prescribed 1.2 (95% confidence interval [CI] = 0.3-2.0) years later among those in the statutory health insurance system compared with those who had private insurance. The lag increased by 0.6 (-0.1 to 1.3) years for every 10 years of patient age. In the age-mix of our sample, access to the health benefits of sumatriptan therapy lagged nearly 1.5 years behind in the statutory health insurance system and for Germany as a whole. Migraine patients' access to sumatriptan therapy lagged substantially in the statutory health insurance system and in the country as a whole. Risk advancement periods provide a useful methodology for communicating major healthcare issues in a meaningful way to society and policymakers.