Knowledge Gaps, Challenges, and Opportunities in Health and Prevention Research for Asian Americans, Native Hawaiians, and Pacific Islanders: A Report From the 2021 National Institutes of Health Workshop.

Asian Americans (AsA), Native Hawaiians, and Pacific Islanders (NHPI) comprise 7.7% of the U.S. population, and AsA have had the fastest growth rate since 2010. Yet the National Institutes of Health (NIH) has invested only 0.17% of its budget on AsA and NHPI research between 1992 and 2018. More than 40 ethnic subgroups are included within AsA and NHPI (with no majority subpopulation), which are highly diverse culturally, demographically, linguistically, and socioeconomically. However, data for these groups are often aggregated, masking critical health disparities and their drivers. To address these issues, in March 2021, the National Heart, Lung, and Blood Institute, in partnership with 8 other NIH institutes, convened a multidisciplinary workshop to review current research, knowledge gaps, opportunities, barriers, and approaches for prevention research for AsA and NHPI populations. The workshop covered 5 domains: 1) sociocultural, environmental, psychological health, and lifestyle dimensions; 2) metabolic disorders; 3) cardiovascular and lung diseases; 4) cancer; and 5) cognitive function and healthy aging. Two recurring themes emerged: Very limited data on the epidemiology, risk factors, and outcomes for most conditions are available, and most existing data are not disaggregated by subgroup, masking variation in risk factors, disease occurrence, and trajectories. Leveraging the vast phenotypic differences among AsA and NHPI groups was identified as a key opportunity to yield novel clues into etiologic and prognostic factors to inform prevention efforts and intervention strategies. Promising approaches for future research include developing collaborations with community partners, investing in infrastructure support for cohort studies, enhancing existing data sources to enable data disaggregation, and incorporating novel technology for objective measurement. Research on AsA and NHPI subgroups is urgently needed to eliminate disparities and promote health equity in these populations.

Collaborative Cohort of Cohorts for COVID-19 Research (C4R) Study: Study Design.

The Collaborative Cohort of Cohorts for COVID-19 Research (C4R) is a national prospective study of adults comprising 14 established US prospective cohort studies. Starting as early as 1971, investigators in the C4R cohort studies have collected data on clinical and subclinical diseases and their risk factors, including behavior, cognition, biomarkers, and social determinants of health. C4R links this pre-coronavirus disease 2019 (COVID-19) phenotyping to information on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and acute and postacute COVID-related illness. C4R is largely population-based, has an age range of 18-108 years, and reflects the racial, ethnic, socioeconomic, and geographic diversity of the United States. C4R ascertains SARS-CoV-2 infection and COVID-19 illness using standardized questionnaires, ascertainment of COVID-related hospitalizations and deaths, and a SARS-CoV-2 serosurvey conducted via dried blood spots. Master protocols leverage existing robust retention rates for telephone and in-person examinations and high-quality event surveillance. Extensive prepandemic data minimize referral, survival, and recall bias. Data are harmonized with research-quality phenotyping unmatched by clinical and survey-based studies; these data will be pooled and shared widely to expedite collaboration and scientific findings. This resource will allow evaluation of risk and resilience factors for COVID-19 severity and outcomes, including postacute sequelae, and assessment of the social and behavioral impact of the pandemic on long-term health trajectories.

Use of the National Heart, Lung, and Blood Institute Data Repository.

BACKGROUND: Research on data sharing from clinical trials has focused on elucidating perceptions, barriers, and attitudes among trialists and study participants with respect to sharing data. However, little information exists regarding utilization or associated publication of articles once clinical trial data have been widely shared. METHODS: We analyzed administrative records of investigator requests for data access, linked publications, and bibliometrics to describe the use of the National Heart, Lung, and Blood Institute data repository. RESULTS: From January 2000 through May 2016, a total of 370 investigators requested data from 1 or more clinical trials. Requests for trial data have been increasing, with 195 investigators (53%) initiating requests during the last 4.4 years of the study period. The predominant reason for requesting data was post hoc secondary analysis of new questions (72%), followed by analytic or statistical approaches to clinical trials (9%) and meta-analyses or pooled study research (7%). Of 172 requests with online project descriptions, only 2 requests were initiated for reanalysis of primary-outcome findings. Data from 88 of 100 available clinical trials were requested at least once, and the median time from repository availability to first request was 235 days. A total of 277 articles were published on the basis of data from 47 trials. Citation metrics from 224 articles indicated that half of the publications have cumulative citations that rank in the top 34% normalized for subject category and year of publication. CONCLUSIONS: Demand for trial data for secondary analysis has been increasing. Requesting data for the a priori purpose of reanalysis or verification of original findings was rare.

Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies.

AIMS: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. METHODS AND RESULTS: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. CONCLUSION: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

Gene-centric association study of acute chest syndrome and painful crisis in sickle cell disease patients.

Patients with sickle cell disease (SCD) present with a wide range of clinical complications. Understanding this clinical heterogeneity offers the prospects to tailor the right treatments to the right patients and also guide the development of novel therapies. Several environmental (eg, nutrition) and nonenvironmental (eg, fetal hemoglobin levels, α-thalassemia status) factors are known to modify SCD severity. To find new genetic modifiers of SCD severity, we performed a gene-centric association study in 1514 African American participants from the Cooperative Study of Sickle Cell Disease (CSSCD) for acute chest syndrome (ACS) and painful crisis. From the initial results, we selected 36 single nucleotide polymorphism (SNPs) and genotyped them for replication in 387 independent patients from the CSSCD, 318 SCD patients recruited at Georgia Health Sciences University, and 449 patients from the Duke SCD cohort. In the combined analysis, an association between ACS and rs6141803 reached array-wide significance (P = 4.1 × 10(-7)). This SNP is located 8.2 kilobases upstream of COMMD7, a gene highly expressed in the lung that interacts with nuclear factor-κB signaling. Our results provide new leads to gaining a better understanding of clinical variability in SCD, a "simple" monogenic disease.

Individual education, area income, and mortality and recurrence of myocardial infarction in a Medicare cohort: the National Longitudinal Mortality Study.

BACKGROUND: The Medicare program provides universal access to hospital care for the elderly; however, mortality disparities may still persist in this population. The association of individual education and area income with survival and recurrence post Myocardial Infarction (MI) was assessed in a national sample. METHODS: Individual level education from the National Longitudinal Mortality Study was linked to Medicare and National Death Index records over the period of 1991-2001 to test the association of individual education and zip code tabulation area median income with survival and recurrence post-MI. Survival was partitioned into 3 periods: in-hospital, discharge to 1 year, and 1 year to 5 years and recurrence was partitioned into two periods: 28 day to 1 year, and 1 year to 5 years. RESULTS: First MIs were found in 8,043 women and 7,929 men. In women and men 66-79 years of age, less than a high school education compared with a college degree or more was associated with 1-5 year mortality in both women (HRR 1.61, 95% confidence interval 1.03-2.50) and men (HRR 1.37, 1.06-1.76). Education was also associated with 1-5 year recurrence in men (HRR 1.68, 1.18-2.41, < High School compared with college degree or more), but not women. Across the spectrum of survival and recurrence periods median zip code level income was inconsistently associated with outcomes. Associations were limited to discharge-1 year survival (RR lowest versus highest quintile 1.31, 95% confidence interval 1.03-1.67) and 28 day-1 year recurrence (RR lowest versus highest quintile 1.72, 95% confidence interval 1.14-2.57) in older men. CONCLUSIONS: Despite the Medicare entitlement program, disparities related to individual socioeconomic status remain. Additional research is needed to elucidate the barriers and mechanisms to eliminating health disparities among the elderly.

Declining severity of myocardial infarction from 1987 to 2002: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Death rates for coronary heart disease have been declining in the United States, but the reasons for this decline are not clear. One factor that could contribute to this decline is a reduction in the severity of acute myocardial infarction (MI). We hypothesized that for those patients hospitalized in the Atherosclerosis Risk in Communities (ARIC) Study with acute incident MI, there was a decline in MI severity from 1987 to 2002. METHODS AND RESULTS: The community surveillance component of the ARIC Study consisted of tracking residents 35 to 74 years of age with hospitalized MI or fatal coronary heart disease in 4 diverse communities. For incident, hospitalized MI, a probability sample of hospital discharges was validated and an MI classification was assigned according to an algorithm consisting of chest pain, ECG evidence, and cardiac biomarkers. Severity indicators were chosen from abstracted hospital charts validated as a definite or probable MI. With few exceptions, the MI severity indicators suggested a significant decline in the severity of MI during the period of 1987 to 2002. The percent of MI cases with major ECG abnormalities decreased as evidenced by a 1.9%/y (P=0.002) decline in the proportion of those with initial ST-segment elevation, a 3.9%/y (P<0.001) decline in those with subsequent Q-waves, and a 4.5%/y (P<0.001) decline in those with any major Q wave. Maximum creatine kinase and creatine kinase-MB values declined (5.2% and 7.6%; P<0.001, P<0.001 per year, respectively), although in the later years, maximum troponin I values remained stable (1.1%/y decline; P=0.66). The percent with shock declined (5.7%/y; P<0.001), although those with congestive heart failure remained stable. A combined severity score, the Predicting Risk of Death in Cardiac Disease Tool (PREDICT) score, also declined (0.2%/y; P<0.001). Results for blacks paralleled those of the entire group, as did results for women. CONCLUSIONS: Evidence from ARIC community surveillance suggests that the severity of acute MI has declined among community residents hospitalized for incident MI. This reduction in severity may have contributed, along with other factors, to the decline in death rates for coronary heart disease.

Trends in all-cause and cardiovascular disease mortality among women and men with and without diabetes mellitus in the Framingham Heart Study, 1950 to 2005.

BACKGROUND: Despite population declines in all-cause mortality, women with diabetes mellitus may have experienced an increase in mortality rates compared with men. METHODS AND RESULTS: We examined change in all-cause, cardiovascular, and non-cardiovascular disease mortality rates among Framingham Heart Study participants who attended examinations during an "earlier" (1950 to 1975; n=930 deaths) and a "later" (1976 to 2001; n=773 deaths) time period. Diabetes mellitus was defined as casual glucose > or =200 mg/dL, fasting plasma glucose > or =126 mg/dL, or treatment. Among women, the hazard ratios (HRs) for all-cause mortality in the later versus the earlier time period were 0.59 (95% confidence interval, 0.50 to 0.70; P<0.0001) for those without diabetes mellitus and 0.48 (95% confidence interval, 0.32 to 0.71; P=0.002) for those with diabetes mellitus. Similar results were observed in men. Among women and men, the HR of cardiovascular disease mortality declined among those with and without diabetes mellitus. Non-cardiovascular disease mortality declined among women without diabetes mellitus (HR, 0.76; P=0.01), whereas no change was observed among women with diabetes mellitus or among men with or without diabetes mellitus. Individuals with versus those without diabetes mellitus were at increased risk of all-cause mortality in the earlier (HR, 2.44; P<0.0001) and later (HR, 1.95; P<0.0001) time periods. CONCLUSIONS: Reductions in all-cause mortality among women and men with diabetes mellitus have occurred over time. However, mortality rates among individuals with diabetes mellitus remain approximately 2-fold higher compared with individuals without diabetes mellitus.

Funding of Hispanic/Latino Health-Related Research by the National Institutes of Health: An Analysis of the Portfolio of Research Program Grants on Six Health Topic Areas.

Hispanics/Latinos are expected to constitute 25% of the U.S. population by 2060. Differences in the prevalence of health risk factors, chronic diseases, and access to and utilization of health-care services between Hispanics/Latinos and other populations in the U.S. have been documented. This study aimed to describe and analyze the landscape of Research Program Grants (RPGs) funded by the National Institutes of Health (NIH) between 2008 and 2015 involving Hispanic/Latino health research in six health condition areas-asthma, cancer, dementia, diabetes, liver/gallbladder disease, and obesity-and to identify opportunities for continued research in these areas. Using an NIH internal search engine, we identified new and renewal Hispanic/Latino health RPGs searching for specific Hispanic/Latino identifiers in the Title, Abstract, and Specific Aims. We used descriptive statistics to examine the distribution of funded RPGs by NIH disease-based classification codes for the six health condition areas of interest, and other selected characteristics. The most prominent clusters of research subtopics were identified within each health condition area, and performance sites were mapped at the city level. Within the selected time frame, 3,221 Hispanic/Latino health-related unique RPGs were funded (constituting 4.4% of all funded RPGs), and of those 625 RPGs were eligible for review and coding in the present study. Cancer and obesity were the most commonly studied health condition areas (72%), while studies on mechanisms of disease-biological and non-biological-(72.6%), behavioral research (42.1%) and epidemiological studies (38.1%) were the most common types of research. Most of the primary performance sites were in California, Texas, the northeastern U.S., and Illinois. The predominance of mechanistic, behavioral, and epidemiological studies in our analysis poses opportunities to evaluate knowledge gained and their clinical application, explore new research questions, or to update some methods or instruments. The findings of the present study suggest opportunities to expand research in understudied mechanisms of disease that could explain differences in prevalence of conditions like diabetes and cancer among different heritage groups. In addition, our findings suggest that the impact of interventions or policies designed to reduce health disparities, innovative multi-level interventions, implementation and dissemination studies, the role of health information technology on health outcomes, and the intersectionality of individual, sociocultural, geographic, and other factors on health outcomes, among others, are understudied approaches, which could potentially advance research in Hispanic/Latino health and contribute to the achievement of better health outcomes in this diverse population.

Trends from 1987 to 2004 in sudden death due to coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: Few data are available on the secular changes in sudden coronary heart disease (CHD) death in US communities. METHODS: We examined trends in sudden CHD death from 1987 to 2004, using data from the Atherosclerosis Risk in Communities (ARIC) study. Sudden CHD deaths in residents of 4 communities aged 35 to 74 years were ascertained using multiple sources such as death certificates, informant and coroner interviews, and physician adjudications. Poisson regression was used to assess the trends for the 6 periods: 1987 to 1989, 1990 to 1992, 1993 to 1995, 1996 to 1998, 1999 to 2001, 2002 to 2004, after adjusting for demographic factors. RESULTS: Overall, 32.6% of CHD deaths were sudden, occurring within an hour after the onset of symptoms, 63.5% of which had no prior diagnosis of CHD. For women, the rate declined by 40% (P = .059) for sudden deaths with CHD history, 27% (P = .067) for those without CHD history, and 39% (P < .001) for nonsudden CHD deaths. The trends did not differ by community. For men, the trends differed by community for sudden deaths with and without CHD history (Ps for the interaction= .019 and .009, respectively) but not for nonsudden CHD death (P for the interaction= .10). For all communities combined, the decline in men was greatest for sudden deaths with CHD history (by 58%, P < .001), followed by nonsudden CHD deaths (by 39%, P < .001) and sudden deaths without CHD history (by 31%, P = .002). However, the proportion of CHD deaths that were sudden had remained stable over time. CONCLUSION: Although the rate of sudden CHD deaths, with and without CHD history, declined over time, the trend pattern may differ by community and gender.

Prevalence and awareness of CKD among African Americans: the Jackson Heart Study.

BACKGROUND: Chronic kidney disease (CKD) leads to end-stage renal disease and is a growing epidemic throughout the world. In the United States, African Americans have an incidence of end-stage renal disease 4 times that of whites. STUDY DESIGN: Cross-sectional to examine the prevalence and awareness of CKD in African Americans. SETTING & PARTICIPANTS: Observational cohort in the Jackson Heart Study (JHS). PREDICTOR: CKD was defined as an estimated glomerular filtration rate less than 60 mL/min/1.73 m(2), the presence of albuminuria, or dialysis therapy. OUTCOMES & MEASUREMENTS: Data from the JHS were analyzed. Medical history, including disease awareness and drug therapy, anthropometric measurements, and serum and urine samples, were obtained from JHS participants at the baseline visit. Associations between CKD prevalence and awareness and selected demographic, socioeconomic, health care access, and disease status parameters were assessed by using logistic regression models. RESULTS: The prevalence of CKD in the JHS was 20%; CKD awareness was only 15.8%. Older participants had a greater prevalence, but also were more aware of CKD. Hypertension, diabetes, cardiovascular disease, hypercholesterolemia, hypertriglyceridemia, increasing age and waist circumference, and being single or less physically active were associated with CKD. Only advancing CKD stage was associated with awareness. LIMITATIONS: Cross-sectional assessment, single urine measurement. CONCLUSIONS: The JHS has a high prevalence and low awareness of CKD, especially in those with less severe disease status. This emphasizes the need for earlier diagnosis and increased education of health care providers and the general population.

Increasing cardiovascular disease burden due to diabetes mellitus: the Framingham Heart Study.

BACKGROUND: Marked reductions in cardiovascular disease (CVD) morbidity and mortality have occurred in the United States over the last 50 years. We tested the hypothesis that the relative burden of CVD attributable to diabetes mellitus (DM) has increased over the past 5 decades. METHODS AND RESULTS: Participants aged 45 to 64 years from the Framingham Heart Study, who attended examinations in an "early" time period (1952 to 1974), were compared with those who attended examinations in a later time period (1975 to 1998). The risk of CVD events (n=133 among those with and 1093 among those without DM) attributable to DM in the 2 time periods was assessed with Cox proportional hazards models; population attributable risk of DM as a CVD risk factor was calculated for each time period. The age- and sex-adjusted hazard ratio for DM as a CVD risk factor was 3.0 (95% CI, 2.3 to 3.9) in the earlier time period and 2.5 (95% CI, 1.9 to 3.2) in the later time period. The population attributable risk for DM as a CVD risk factor increased from 5.4% (95% CI, 3.8% to 6.9%) in the earlier time period to 8.7% (95% CI, 5.9% to 11.4%) in the later time period (P for attributable risk ratio=0.04), although multivariable adjustment resulted in attenuation of these findings (P=0.12); most of these observations were found among men. CONCLUSIONS: The proportion of CVD attributable to DM has increased over the past 50 years in Framingham. These findings emphasize the need for increased efforts to prevent DM and to aggressively treat and control CVD risk factors among those with DM.

Effect of statin therapy on survival in patients with nonischemic dilated cardiomyopathy (from the Beta-blocker Evaluation of Survival Trial [BEST]).

To determine whether statin therapy improves survival in patients with heart failure (HF) secondary to nonischemic dilated cardiomyopathy (non-IDC), data from 1,024 patients with non-IDC (New York Heart Association functional class III and IV HF) and left ventricular ejection fraction < or =0.35 who were enrolled in the BEST were analyzed. The association of statin therapy at the initial screening visit with all-cause and cardiovascular mortality was evaluated using multivariate Cox proportional hazards models. After adjusting for age, gender, race, systolic blood pressure, total cholesterol, New York Heart Association functional class IV, estimated glomerular filtration rate, current cigarette smoking, left ventricular ejection fraction, angiotensin-converting enzyme inhibitor use, antiplatelet therapy, diabetes mellitus, treatment group (beta blocker or placebo), and hypertension, statin use was independently associated with decreased all-cause mortality (hazard ratio 0.38, confidence interval 0.18 to 0.82, p = 0.0134) and also with decreased cardiovascular death (hazard ratio 0.42, confidence interval 0.18 to 0.95, p = 0.037). In conclusion, in patients with moderate or severe HF due to non-IDC entered into BEST, statin therapy at entry was independently associated with a decrease in all-cause and cardiovascular mortality.

The Productivity of NHLBI-Funded Obesity Research, 1983-2013.

OBJECTIVE: To describe and elucidate the time trends of the academic productivity of NHLBI's obesity-related research funding via bibliometric analysis of 30 years of NHLBI-supported obesity-related publications. METHODS: In total, 3,545 NHLBI-funded obesity-related publications were identified in the Thomson Reuters InCites™ database. Shared references in a community detection algorithm were used to identify publication topics. Characteristics of publications and topical communities were analyzed based on citation count and percentile rank. A percentile rank >90 was considered "highly cited." RESULTS: Obesity-related publications increased more than 10-fold over 30 years, whereas NHLBI-funded publications only increased twofold NHLBI-funded obesity publications were cited a median of 23 times (IQR 8-55, range 0-2,047, mean 52). Thirty percent of these publications were highly cited compared to the expected ten percent. Six topical communities were present in 1983 compared to 16 in 2013. The most highly cited topical areas were sleep (n = 199 publications, 38% highly cited), cardiovascular morbidity and mortality (n = 277, 36%), obesity correlates and consequences (n = 588, 35%), and asthma and inflammation (n = 283, 35%). CONCLUSIONS: NHLBI-funded obesity publications have contributed substantially to the obesity literature, with many highly cited. Publications grew in number and topical diversity over 30 years and grew at a faster rate than total NHLBI publications.

Providing Contemporary Access to Historical Biospecimen Collections: Development of the NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).

The National Heart, Lung, and Blood Institute (NHLBI), within the United States' National Institutes of Health (NIH), established a Biorepository in 1976 that initially archived biospecimens from population-based blood product safety surveys. It was later expanded to biospecimens from clinical and epidemiological studies in heart, lung, and blood disorders. The NHLBI also established a Data Repository in 2000 to store and distribute study data from NHLBI-sponsored research. The NHLBI Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC) was established in 2008 to develop the infrastructure needed to link the contents of these two related NHLBI Repositories, facilitate access to repository resources, and streamline request processes. Three key program subcomponents were developed simultaneously: 1) the linkage of biospecimen electronic inventory records with their clinical or characterization data; 2) the development and implementation of a website with both public-facing information and private processing workspaces; and 3) the development of processes to maximize efficiency via a web-based system while maintaining workflow control, document tracking, and secure processes. The BioLINCC website was launched on October 1, 2009 with eight biospecimen collections and data from 72 research studies. By the end of the fourth online year, 38 biospecimen collections were linked and posted, and data from 108 research studies had been made available for request. The number of registered users by the end of the fourth online year approached 2600, and continues to show a trend towards an increasing rate of new users per year. BioLINCC has fulfilled 381 requests comprising 851 data collections, as well as 600 teaching dataset requests and 75 data renewal agreements. 154 biospecimen requests comprising 147,388 biospecimens were fulfilled or actively in process. We conclude that the BioLINCC program has been successful in its goal to increase the visibility and utilization of NHLBI biospecimen and data repository resources.

Duration and Degree of Weight Gain and Incident Diabetes in Younger Versus Middle-Aged Black and White Adults: ARIC, CARDIA, and the Framingham Heart Study.

OBJECTIVE: To determine whether duration and degree of weight gain are differentially associated with diabetes risk in younger versus middle-aged black and white adults. RESEARCH DESIGN AND METHODS: We combined data from three cohort studies: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and the Framingham Heart Study. A total of 17,404 participants (56% women; 21% black) were stratified by baseline age (younger: ≥30 and <45 years; middle-aged: ≥45 and <60 years) and examined for incident diabetes (median follow-up 9 years). Duration and degree of gain in BMI were calculated as "BMI-years" above one's baseline BMI. RESULTS: Diabetes incidence per 1,000 person-years in the younger and middle-aged groups was 7.2 (95% CI 5.7, 8.7) and 24.4 (22.0, 26.8) in blacks, respectively, and 3.4 (2.8, 4.0) and 10.5 (9.9, 11.2) in whites, respectively. After adjusting for sex, baseline BMI and other cardiometabolic factors, and age and race interaction terms, gains in BMI-years were associated with higher risk of diabetes in the younger compared with middle-aged groups: hazard ratios for 1-unit increase in log BMI-years in younger versus middle-aged blacks were 1.18 (P = 0.02) and 1.02 (P = 0.39), respectively (P for interaction by age-group = 0.047), and in whites were 1.35 (P < 0.001) and 1.11 (P < 0.001), respectively (P for interaction by age-group = 0.008). CONCLUSIONS: Although middle-aged adults have higher rates of diabetes, younger adults are at greater relative risk of developing diabetes for a given level of duration and degree of weight gain.

Smoking and diabetes differ in their associations with subclinical atherosclerosis and coronary heart disease-the ARIC Study.

Atherosclerosis, nearly universally present in major arteries of Western adults, is characterized in all affected arteries by cholesterol-laden plaques and consistently associated with blood cholesterol levels. Other risk factors are reported to have relatively stronger or weaker associations with different atherosclerotic manifestations, but such differences have never previously been quantified. Measuring them may offer fresh clues to atherogenic processes and their prevention. The Atherosclerosis Risk in Communities Study (ARIC) ascertained incident coronary heart disease (CHD) and measured subclinical atherosclerosis as carotid artery intimal medial thickness using ultrasound and as lower extremity arterial disease (LEAD) using ankle-brachial blood pressure index. Blood cholesterol was associated with all endpoints. When standardized against LDL cholesterol associations, diabetes and smoking showed substantially different strengths of associations with different endpoints. Relative to associations with LDL cholesterol: (1) smoking, but not diabetes, increased in its strength of association with the severity of the underlying arterial disease; (2) the diabetes and smoking associations with CHD were much stronger in women than men, a phenomenon which, the standardization pattern suggests, is due to a gender difference in CHD pathogenesis, possibly attributable to arteriolar differences.