Aruna Kamineni

Lifestyle Risk Factors and New-Onset Diabetes Mellitus in Older Adults: The Cardiovascular Health Study

BACKGROUND The combined impact of lifestyle factors on incidence of diabetes mellitus later in life is not well established. The objective of this study was to determine how lifestyle factors, assessed in combination, relate to new-onset diabetes in a broad and relatively unselected population of older adults. METHODS We prospectively examined associations of lifestyle factors, measured using repeated assessments later in life, with incident diabetes mellitus during a 10-year period (1989-1998) among 4883 men and women 65 years or older (mean [SD] age at baseline, 73 [6] years) enrolled in the Cardiovascular Health Study. Low-risk lifestyle groups were defined by physical activity level (leisure-time activity and walking pace) above the median; dietary score (higher fiber intake and polyunsaturated to saturated fat ratio, lower trans-fat intake and lower mean glycemic index) in the top 2 quintiles; never smoked or former smoker more than 20 years ago or for fewer than 5 pack-years; alcohol use (predominantly light or moderate); body mass index less than 25 (calculated as weight in kilograms divided by height in meters squared); and waist circumference of 88 cm for women or 92 cm for men. The main outcome measure was incident diabetes defined annually by new use of insulin or oral hypoglycemic medications. We also evaluated fasting and 2-hour postchallenge glucose levels. RESULTS During 34,539 person-years, 337 new cases of drug-treated diabetes mellitus occurred (9.8 per 1000 person-years). After adjustment for age, sex, race, educational level, and annual income, each lifestyle factor was independently associated with incident diabetes. Overall, the rate of incident diabetes was 35% lower (relative risk, 0.65; 95% confidence interval, 0.59-0.71) for each 1 additional lifestyle factor in the low-risk group. Participants whose physical activity level and dietary, smoking, and alcohol habits were all in the low-risk group had an 82% lower incidence of diabetes (relative risk, 0.18; 95% confidence interval, 0.06-0.56) compared with all other participants. When absence of adiposity (either body mass index <25 or waist circumference < or =88/92 cm for women/men) was added to the other 4 low-risk lifestyle factors, incidence of diabetes was 89% lower (relative risk, 0.11; 95% confidence interval, 0.01-0.76). Overall, 9 of 10 new cases of diabetes appeared to be attributable to these 5 lifestyle factors. Associations were slightly attenuated, but still highly significant, for incident diabetes defined by medication use or glucose level. CONCLUSION Even later in life, combined lifestyle factors are associated with a markedly lower incidence of new-onset diabetes mellitus.

Metabolic Syndrome and Mortality in Older Adults: The Cardiovascular Health Study

BACKGROUND The utility of metabolic syndrome (MetS) for predicting mortality among older adults, the highest-risk population, is not well established. In addition, few studies have compared the predictive utility of MetS to that of its individual risk factors. METHODS We evaluated relationships of MetS (as defined by the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults [Adult Treatment Panel III (ATPIII)], International Diabetes Foundation [IDF], and World Health Organization [WHO]) and individual MetS criteria with mortality between 1989 and 2004 among 4258 US adults 65 years or older and free of prevalent cardiovascular disease (CVD) in the Cardiovascular Health Study, a multicenter, population-based, prospective cohort. Total, CVD, and non-CVD mortality were evaluated. Cox proportional hazards models were used to estimate the mortality hazard ratio (relative risk [RR]) predicted by MetS. RESULTS At baseline (mean age, 73 years), 31% of men and 38% of women had MetS (ATPIII). During 15 years of follow-up, 2116 deaths occurred. After multivariable adjustment, compared with persons without MetS, those with MetS had a 22% higher mortality (RR, 1.22; 95% confidence interval [CI], 1.11-1.34). Higher risk with MetS was confined to persons having elevated fasting glucose level (EFG) (defined as > or = 110 mg/dL [> or = 6.1 mmol/L] or treated diabetes mellitus) (RR, 1.41; 95% CI, 1.27-1.57) or hypertension (RR, 1.26; 95% CI, 1.15-1.39) as one of the criteria; persons having MetS without EFG (RR, 0.97; 95% CI, 0.85-1.11) or MetS without hypertension (RR, 0.92; 95% CI, 0.71-1.19) did not have higher risk. Evaluating MetS criteria individually, we found that only hypertension and EFG predicted higher mortality; persons having both hypertension and EFG had 82% higher mortality (RR, 1.82; 95% CI, 1.58-109). Substantially higher proportions of deaths were attributable to EFG and hypertension (population attributable risk fraction [PAR%], 22.2%) than to MetS (PAR%, 6.3%). Results were similar when we used WHO or IDF criteria, when we evaluated different cut points of each individual criterion, and when we evaluated CVD mortality. CONCLUSION These findings suggest limited utility of MetS for predicting total or CVD mortality in older adults compared with assessment of fasting glucose and blood pressure alone.

Childbearing and survival after breast carcinoma in young women

Many young patients with breast carcinoma have not started, or completed, their desired families. How childbearing after a diagnosis of breast carcinoma affects survival is of importance to these women and their families. The authors measured relative mortality among young patients with breast carcinoma with and without births occurring after diagnosis.

Screening Colonoscopy and Risk for Incident Late-Stage Colorectal Cancer Diagnosis in Average-Risk Adults: A Nested Case–Control Study

BACKGROUND The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer. OBJECTIVE To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC). DESIGN Nested case-control study. SETTING Four U.S. health plans. PATIENTS 1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration. MEASUREMENTS Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures. RESULTS In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer. LIMITATION The small number of screening colonoscopies affected the precision of the estimates. CONCLUSION Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant.

Pregnancy outcomes in female childhood and adolescent cancer survivors: a linked cancer-birth registry analysis.

OBJECTIVE To compare birth outcomes among female survivors of childhood and adolescent cancer who subsequently bear children, relative to those of women without a history of cancer. DESIGN Retrospective cohort study. SETTING Four US regions. PARTICIPANTS Cancer registries identified girls younger than 20 years who were diagnosed as having cancer from 1973 through 2000. Linked birth records identified the first live births after diagnosis (n = 1898). Comparison subjects were selected from birth records (n = 14 278). Survivors of genital tract carcinomas underwent separate analysis. MAIN EXPOSURE Cancer diagnosis at younger than 20 years. MAIN OUTCOME MEASURES Infant low birth weight, preterm delivery, sex ratio, malformations, mortality, and delivery method, and maternal diabetes, anemia, and preeclampsia. RESULTS Infants born to childhood cancer survivors were more likely to be preterm (relative risk [RR], 1.54; 95% confidence interval [CI], 1.30-1.83) and to weigh less than 2500 g (1.31; 1.10-1.57). For the offspring of genital tract carcinoma survivors, RRs were 1.33 (95% CI, 1.13-1.56) and 1.29 (1.10-1.53), respectively. There were no increased risks of malformations, infant death, or altered sex ratio, suggesting no increased germ cell mutagenicity. In exploratory analysis, bone cancer survivors had an increased risk of diabetes (RR, 4.92; 95% CI, 1.60-15.13), and anemia was more common among brain tumor survivors (3.05; 1.16-7.98) and childhood cancer survivors whose initial treatment was chemotherapy only (2.45; 1.16-5.17). CONCLUSIONS Infants born to female survivors of childhood and adolescent cancer were not at increased risk of malformations or death. Increased occurrence of preterm delivery and low birth weight suggest that close monitoring is warranted. Increased diabetes and anemia among subgroups have not been reported, suggesting areas for study.

Risk Factor Differences for Aortic Versus Coronary Calcified Atherosclerosis: The Multiethnic Study of Atherosclerosis

Objective—The goal of this study was to compare and contrast coronary artery calcium (CAC) with abdominal aortic calcium (AAC) in terms of their associations with traditional and novel cardiovascular disease (CVD) risk factors. Methods and Results—We measured both AAC and CAC using computed tomography scans in 1974 men and women aged 45 to 84 years from a multiethnic cohort. Traditional and novel CVD risk factors were examined separately in relation to AAC and CAC, using logistic regression for qualitative categorical comparisons and multiple linear regression for quantitative continuous comparisons. AAC was significantly associated with cigarette smoking and dyslipidemia and showed no gender difference. In contrast, CAC showed much weaker associations with smoking and dyslipidemia and a strong male predominance. Age and hypertension were associated similarly and significantly with AAC and CAC. Novel risk factors generally showed no independent association with either calcium measure, although in subset analyses, phosphorus, but not calcium, was related to CAC. The receiver operating characteristic curves for the qualitative results and the r2 values for the quantitative analyses were both much higher for AAC than for CAC. Conclusion—AAC showed stronger correlations with most CVD risk factors than did CAC. The predictive value of AAC compared with CAC for incident CVD events remains to be evaluated.

The Epidemiology of Subclavian Stenosis and its Association with Markers of Subclinical Atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA)

BACKGROUND Recent studies indicate that subclavian stenosis (SS), diagnosed by a large systolic blood pressure difference (SBPD) between the right and left brachial arteries, is associated with cardiovascular disease (CVD) risk factors and outcomes. We sought to describe the epidemiology of SS and determine its association with markers of subclinical CVD in the baseline cohort of the Multi-Ethnic Study of Atherosclerosis. METHODS We defined SS by an absolute SBPD>or=15 mmHg. Peripheral artery disease (PAD) was defined by an ankle-brachial index<or=0.90. The coronary artery calcium score (CAC) and the common carotid artery intima-media thickness (CCA-IMT) were measured by computed tomography and B-mode ultrasound, respectively. Odds ratios for the associations of SS with risk factors and subclinical disease were estimated using logistic regression. RESULTS Of 6743 subjects studied, 307 participants (4.6%) had SS, with a higher prevalence in women (5.1%) than men (3.9%), and in African Americans (7.4%) and non-Hispanic whites (5.1%) than Hispanic (1.9%) or Chinese (1.0%) participants (p<0.01). In a model including age, gender, ethnicity, traditional and novel CVD risk factors, significant associations with SS were observed for C-reactive protein (highest vs. three lower quartiles: OR=1.41; 95%CI: 1.06-1.87) and brachial artery pulse pressure (OR=1.12/10 mmHg; 95%CI: 1.03-1.21). Adjusted for age, gender, ethnicity, traditional and novel CVD risk factors, SS was significantly associated with PAD (OR=2.35; 1.55-3.56), with CCA-IMT (highest vs. the lower three quartiles: OR=1.32; 1.00-1.75), and high CAC (score>100 vs. score=0; OR=1.43; 1.03-2.01). CONCLUSIONS The subclavian stenosis is positively associated with other markers of subclinical atherosclerosis.

Egg consumption and risk of type 2 diabetes in older adults

BACKGROUND Type 2 diabetes (T2D) remains an important public health issue in the United States. There are limited and inconsistent data on the association between egg consumption and fasting glucose or incident diabetes. OBJECTIVES We assessed the association between egg intake and incident diabetes in older adults. DESIGN In this prospective study of 3898 men and women from the Cardiovascular Health Study (1989-2007), we assessed egg consumption by using a picture-sorted food questionnaire and ascertained incident T2D annually by using information on hypoglycemic agents and plasma glucose. We used Cox proportional hazards models to estimate adjusted relative risks. RESULTS During a mean follow-up of 11.3 y, 313 new cases of T2D occurred. Crude incidence rates of T2D were 7.39, 6.83, 7.00, 6.72, and 12.20 per 1000 person-years in people who reported egg consumption of never, <1 egg/mo, 1-3 eggs/mo, 1-4 eggs/wk, and almost daily, respectively. In multivariable-adjusted models, there was no association between egg consumption and increased risk of T2D in either sex and overall. In a secondary analysis, dietary cholesterol was not associated with incident diabetes (P for trend = 0.47). In addition, egg consumption was not associated with clinically meaningful differences in fasting glucose, fasting insulin, or measures of insulin resistance despite small absolute analytic differences that were significant. CONCLUSION In this cohort of older adults with limited egg intake, there was no association between egg consumption or dietary cholesterol and increased risk of incident T2D.

Reproductive outcomes in male childhood cancer survivors: a linked cancer-birth registry analysis

OBJECTIVE To compare the risk of reproductive and infant outcomes between male childhood cancer survivors and a population-based comparison group. DESIGN Retrospective cohort study. SETTING Four US regions. PARTICIPANTS Cancer registries identified males younger than 20 years diagnosed with cancer from 1973 to 2000. Linked birth certificates identified first subsequent live offspring (N = 470). Comparison subjects were identified from remaining birth certificates, frequency-matched on year and age at fatherhood, and race/ethnicity (N = 4150). MAIN EXPOSURE Cancer diagnosis before age 20 years. OUTCOME MEASURES Pregnancy and infant outcomes identified from birth certificates. RESULTS Compared with infants born to unaffected males, offspring of cancer survivors had a borderline risk of having a birth weight less than 2500 g (relative risk, 1.43 [95% confidence interval, 0.99-2.05]) that was associated most strongly with younger age at cancer diagnosis and exposure to any chemotherapy (1.96 [1.22-3.17]) or radiotherapy (1.95 [1.14-3.35]). However, they were not at risk of being born prematurely, being small for gestational age, having malformations, or having an altered male to female ratio. Overall, female partners of male survivors were not more likely to have maternal complications recorded on birth records vs the comparison group. However, preeclampsia was associated with some cancers, especially central nervous system tumors (relative risk, 3.36 [95% confidence interval, 1.63-6.90]). CONCLUSIONS Most pregnancies resulting in live births among partners of male childhood cancer survivors were not at significantly greater risk of complications vs comparison subjects. However, there remains the possibility that prior cancer therapy may affect male germ cells with some effects on progeny and on female partners.

Time to colonoscopy after positive fecal blood test in four U.S. health care systems

Background: To reduce colorectal cancer mortality, positive fecal blood tests must be followed by colonoscopy. Methods: We identified 62,384 individuals ages 50 to 89 years with a positive fecal blood test between January 1, 2011 and December 31, 2012 in four health care systems within the Population-Based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. We estimated the probability of follow-up colonoscopy and 95% confidence intervals (CI) using the Kaplan–Meier method. Overall differences in cumulative incidence of follow-up across health care systems were assessed with the log-rank test. HRs and 95% CIs were estimated from multivariate Cox proportional hazards models. Results: Most patients who received a colonoscopy did so within 6 months of their positive fecal blood test, although follow-up rates varied across health care systems (P <0.001). Median days to colonoscopy ranged from 41 (95% CI, 40–41) to 174 (95% CI, 123–343); percent followed-up by 12 months ranged from 58.1% (95% CI, 51.6%–63.7%) to 83.8% (95% CI, 83.4%–84.3%) and differences across health care systems were also observed at 1, 2, 3, and 6 months. Increasing age and comorbidity score were associated with lower follow-up rates. Conclusion: Individual characteristics and health care system were associated with colonoscopy after positive fecal blood tests. Patterns were consistent across health care systems, but proportions of patients receiving follow-up varied. These findings suggest that there is room to improve follow-up of positive colorectal cancer screening tests. Impact: Understanding the timing of colonoscopy after positive fecal blood tests and characteristics associated with lack of follow-up may inform future efforts to improve follow-up. Cancer Epidemiol Biomarkers Prev; 25(2); 344–50. ©2016 AACR.