10009 Background: Older adults are a growing segment of our oncology population, with an expected increase in cancer incidence of 67% from 2010 to 2030 in people age 65 and older. However, older adults have been proportionally underrepresented in clinical trials. We sought to analyze the age-related enrollment of cancer patients onto trials supporting registration of new drugs or new indications approved by the US Food and Drug Administration from 2005 to 2015. Methods: This study involved retrospective analyses of demographic data of cancer patients enrolled onto trials supporting registration from 2005-2015. The data on 224,766 cancer patients supporting 105 drug applications were analyzed according to age distributions of <65, 65-69, 70-74, 75-79, and ≥80 years. The rates of enrollment were compared with the corresponding rates in the US cancer population. The age distributions of the US cancer population were derived from the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute for the year 2013 based on the 2010 US Census. Conclusions: Older adults were under-represented in the registration trials of new cancer therapies, especially those over age 75. Various strategies may be needed to evaluate cancer therapies for older adults in prospective clinical trials and to improve cancer care in adults over age 75. These include re-evaluating what may be considered restrictive eligibility criteria so as not to exclude older adults. Incorporating elements from geriatric assessment tools may help identify older adults most likely to benefit from treatment. More detailed labeling information that reflects the clinical experience with older adults could be considered. The FDA encourages drug sponsors as well as clinical trial cooperative groups to devise strategies to recruit patients that are reflective of their intended population. [Table: see text]

BackgroundThe role of coronary artery calcium (CAC) as a screening tool for cardiovascular disease (CVD) risk in African Americans (AAs) is unclear. We compared the diagnostic accuracy for CVD prevalence using the CAC score and the Framingham Risk Score (FRS) in an adult population of AAs.MethodsCAC was measured in 2944 participants AAs. Approximately 8% of this cohort had known CVD defined as prior myocardial infarction, stroke, percutaneous coronary intervention, coronary artery bypass grafting and peripheral artery disease. Logistic regression, receiver operating characteristic (ROC) and net reclassification index (NRI) analysis were used adjusting for age, gender, systolic blood pressure (SBP), total and high-density lipoprotein (HDL) cholesterol, smoking status, diabetes mellitus (DM), body mass index (BMI), blood pressure medication and statin use. Participants with prevalent clinical CVD and DM were classified as high FRS risk.ResultsThe mean age of participants was 60 years, 65% were females, 26% had DM, 50% were obese and 30% were current or former smokers. Prevalent CVD was associated with older age, higher SBP, lower HDL and total cholesterol, and higher CAC. The prevalence of CAC was 83% in participants with prevalent CVD and 45% in those without CVD. CAC was independently associated with prevalent CVD in our multivariable model [OR (95% CI): 1.22 (1.12–1.32), p< 0.0001]. In ROC analysis, CAC improved the diagnostic accuracy (c statistic) of the FRS from 0.617 to 0.757 (p < 0.0001) for prevalent CVD. Addition of CAC to FRS resulted in net reclassification improvement of 4% for subjects with known CVD and 28.5% in those without CVD.ConclusionIn AAs, CAC is independently associated with prevalent CVD and improves the diagnostic accuracy of FRS for prevalent CVD by 14%. Addition of CAC improves the NRI of those with prevalent CVD by 4% and the NRI of individuals without CVD by 28.5%. Determination of CAC may be useful in CVD risk stratification in AAs.

The effect of dietary isoflavone intake on systolic blood pressure (SBP) has not been studied in a large community-based cohort inclusive of African Americans. We analyzed data from the year 20 exam of the Coronary Artery Risk Development in Young Adults (CARDIA) study, including medical history, physical exam and dietary intake surveys for 3,142 participants. Multivariable linear regression models controlled for age, sex, BMI, smoking, physical activity, and intakes of alcohol and total energy. Effect modification by race was tested. Overall, those with hypertension had a lower daily intake of total dietary isoflavones (2.2±5.2 vs. 4.1±11.7 mg/day; p-value <0.001). In fully adjusted models, the highest quartile of dietary isoflavone intake was associated with a 4.4 mmHg lower SBP on average compared with SBP for the lowest quartile. The relation between dietary isoflavone intake and SBP was more pronounced among African Americans, compared to Caucasians (p-for interaction <0.001). Greater dietary intake of isoflavones was independently associated with a lower SBP.

Previous research suggests that visceral adipose tissue (VAT) increases risk for atherosclerosis and specifically arterial calcification, yet the association of subcutaneous adipose tissue (SAT) with calcification is less substantiated. Studies have also noted important race and sex differences in risk of atherosclerosis. In the Family Heart Study, we examined race and sex differences in the pattern of associations of abdominal fat depots with coronary (CAC) and abdominal aorto-iliac (AAC) calcified plaque measured using computed tomography (CT). Methods- We used CT to measure abdominal fat volume and arterial calcified plaque in 2,748 participants of European American descent (EA; n=1512 females) and 626 participants of African American descent (AA; n=412 females) in the Family Heart Study. CAC and AAC were defined as present (≥1) or absent (0) based on Agatston scores. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined using logistic regression models adjusted for age, field center, family pedigree, race, and history of coronary heart disease (CHD), diabetes, hypertension, hypercholesterolemia, and smoking. Results- The association of SAT and VAT with prevalent CAC and AAC varied with sex and race in multivariable logistic regression models. In males, SAT was strongly associated with both CAC (p=0.001) and AAC (p<0.001) in multivariable models and there was evidence that the associations of SAT with CAC and AAC differed by race (each p interaction SAT*race p<0.01). The associations of SAT with CAC and AAC appeared to be stronger in EA males than in AA males. In EA, the OR for CAC for a single SD increase in SAT was 2.17 (95% CI 1.37-3.45) whereas for AA the OR was 1.42 (95% CI 1.17-1.72) per SD increase in SAT. Also, in EA males the OR for AAC per SD increase in SAT was 2.69 (95% CI 1.61-4.50) compared to 1.39 (95% CI 1.11-1.73) in AA males. VAT was significantly associated with prevalent CAC in both EA males (OR=1.96 per SD increase, p=0.02) and AA males (OR=1.26 per SD increase, p=0.02) though there were no significant associations of VAT with AAC among males. In females, both SAT (OR=1.18 per SD increase, p=0.004) and VAT (OR=1.21 per SD increase, p=0.003) were associated with prevalent CAC, but not AAC, in multivariable models and associations did not vary by race. Conclusions- Abdominal SAT was associated with both CAC and AAC prevalence in males, and associations appeared to be stronger in EA compared to AA participants. VAT was predictive of CAC in both EA and AA males. In contrast, SAT and VAT were only associated with CAC in females and no differences by race were noted. Our findings suggest that SAT, and by inference obesity, along with VAT may be an important contributors to prevalence of arterial calcification and that race plays a role in associations among males.

Background: Prior studies suggest that African Americans (AA) have lower prevalence of coronary artery calcium (CAC) compared to whites, yet CAC has similar ability to predict coronary heart disease (CHD) events. The role of CAC as a screening tool for CHD risk in AA is unclear. We compared the diagnostic accuracy for CHD prevalence using the CAC score and the Framingham Risk Score (FRS) in an adult population of AA. Methods: CAC was measured in 2944 participants in the Jackson Heart Study, an NHLBI funded study of AA based in Jackson, MS. Approximately 8% of this cohort had known cardiovascular disease (CVD) defined as prior MI, angina, stroke, PTCA, CABG or PVD. Logistic regression, ROC and net reclassification index (NRI) analysis were used adjusting for age, gender, SBP, total and HDL cholesterol, smoking status, DM and BMI. FRS was calculated and those with DM were classified as high risk. Results: The mean age was 60, 65% were females, 26% had DM, 50% were obese and 30% were current or former smokers. Prevalent CVD was associated with older age, higher SBP, lower HDL and total cholesterol, and higher CAC. CAC was independently associated with prevalent CVD in our multivariable model [OR (95% CI): 1.26 (1.17, 1.35), p< 0.0001]. In ROC analysis, CAC improved the diagnostic accuracy (c statistic) of the FRS from 0.617 to 0.757 (p < 0.0001) for prevalent CVD. The FRS classified 30% of the cohort as high risk, 38.5% as intermediate risk and 31.5% as low risk. FRS classfied 51% of subjects with prevalent CVD as high risk. Addition of CAC to FRS resulted in net reclassification improvement of 4% for subjects with known CVD and 28.5% in those without CVD (see figure). Conclusion: In AA, the CAC is independently associated with prevalent CVD and improves the diagnostic accuracy of FRS for prevalent CVD by 14%. Addition of CAC improves the NRI of those with prevalent CVD by 4% and the NRI of individuals without CVD by 28.5%. Determination of CAC in AA may be useful in identifying individuals at risk of CVD and reclassifying individuals with low and intermediate FRS.