Lifetime Risk of Lower-Extremity Peripheral Artery Disease Defined by Ankle-Brachial Index in the United States.

Background There are no available lifetime risk estimates of lower-extremity peripheral artery disease (PAD). Methods and Results Using data from 6 US community-based cohorts and the vital statistics, we estimated the prevalence and incidence of PAD, defined as an ankle-brachial index < 0.90, at each year of age from birth to 80 years for white, black, and Hispanic men and women. Then, we used Markov Monte Carlo simulations in a simulated cohort of 100 000 individuals to estimate lifetime risk of PAD. On the basis of odds ratios of PAD for traditional atherosclerotic risk factors (eg, diabetes mellitus and smoking), we developed a calculator providing residual lifetime risk of PAD. In an 80-year horizon, lifetime risks of PAD were 30.0% in black men and 27.6% in black women, but ≈19% in white men and women and ≈22% in Hispanic men and women. From another perspective, 9% of blacks were estimated to develop PAD by 60 years of age, while the same proportion was seen at ≈70 years for whites and Hispanics. The residual lifetime risk within the same race/ethnicity varied by 3.5- to 5-fold according to risk factors (eg, residual lifetime risk in 45-year-old black men was 19.9% when current smoking, diabetes mellitus, and history of cardiovascular disease were absent versus 70.4% when all were present). Conclusions In the United States, ≈30% of blacks are estimated to develop PAD during their lifetime, whereas the corresponding estimate is ≈20% for whites and Hispanics. The residual lifetime risk within the same race/ethnicity substantially varies according to traditional risk factors

Iterative Outlier Removal: A Method for Identifying Outliers in Laboratory Recalibration Studies

Extreme values that arise for any reason, including through non-laboratory measurement procedure-related processes (inadequate mixing, evaporation, mislabeling), lead to outliers and inflate errors in recalibration studies. We present an approach termed iterative outlier removal (IOR) for identifying such outliers

Orthostatic Hypotension in Middle-Age and Risk of Falls

One-third of older adults fall each year. Orthostatic hypotension (OH) has been hypothesized as an important risk factor for falls, but findings from prior studies have been inconsistent

Prediabetes and Diabetes Are Associated With Arterial Stiffness in Older Adults: The ARIC Study

To determine whether prediabetes and diabetes in older adults are associated with arterial stiffness measured in central and peripheral arteries and to examine characteristics that modify these associations

Myocardial Injury, Obesity, and the Obesity Paradox

To examine whether pre-heart failure (HF) myocardial injury explains the differential mortality after HF across weight categories

Identification of Incident CKD Stage 3 in Research Studies

In epidemiologic research, incident chronic kidney disease (CKD) is commonly determined by laboratory tests performed at planned study visits. Given the morbidity and mortality associated with CKD, persons with incident disease may be less likely to attend scheduled visits, affecting observed associations. The objective of this study was to quantify loss-to-follow-up by CKD status, and to determine whether supplementation with diagnostic code data improves capture of incident CKD

Hyperglycemia and arterial stiffness: The Atherosclerosis Risk in the Communities study

Hyperglycemia has been associated with an increased risk of cardiovascular morbidity and mortality. Although numerous studies have demonstrated that hyperglycemia is associated with the atherosis component of atherosclerosis, limited studies have addressed the independent role of hyperglycemia in the pathophysiology of sclerotic vascular disease. We hypothesized that hyperglycemia, as assessed by hemoglobin A1c (HbA1c), would be independently associated two common indices of arterial stiffness (pressure-strain elastic modulus (Ep) and Young’s elastic modulus (YEM))

Socioeconomic status and the trajectory of self-rated health

Background: self-rated health (SRH) likely reflects both mental and physical health domains, and is assessed by asking individuals to describe their health status. Poor SRH is associated with disease incidence and subsequent mortality. Changes in SRH across time in persons with different incident diseases are uncharacterised

Recalibration of Blood Analytes over 25 Years in the Atherosclerosis Risk in Communities Study: Impact of Recalibration on Chronic Kidney Disease Prevalence and Incidence

BACKGROUND: Equivalence of laboratory tests over time is important for longitudinal studies. Even a small systematic difference (bias) can result in substantial misclassification. METHODS: We selected 200 Atherosclerosis Risk in Communities Study participants attending all 5 study visits over 25 years. Eight analytes were remeasured in 2011-2013 from stored blood samples from multiple visits: creatinine, uric acid, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, and high-sensitivity C-reactive protein. Original values were recalibrated to remeasured values with Deming regression. Differences >10% were considered to reflect substantial bias, and correction equations were applied to affected analytes in the total study population. We examined trends in chronic kidney disease (CKD) pre- and postrecalibration. RESULTS: Repeat measures were highly correlated with original values [Pearson r > 0.85 after removing outliers (median 4.5% of paired measurements)], but 2 of 8 analytes (creatinine and uric acid) had differences >10%. Original values of creatinine and uric acid were recalibrated to current values with correction equations. CKD prevalence differed substantially after recalibration of creatinine (visits 1, 2, 4, and 5 prerecalibration: 21.7%, 36.1%, 3.5%, and 29.4%, respectively; postrecalibration: 1.3%, 2.2%, 6.4%, and 29.4%). For HDL cholesterol, the current direct enzymatic method differed substantially from magnesium dextran precipitation used during visits 1-4. CONCLUSIONS: Analytes remeasured in samples stored for approximately 25 years were highly correlated with original values, but 2 of the 8 analytes showed substantial bias at multiple visits. Laboratory recalibration improved reproducibility of test results across visits and resulted in substantial differences in CKD prevalence. We demonstrate the importance of consistent recalibration of laboratory assays in a cohort study

Serum metabolites reflecting gut microbiome alpha diversity predict type 2 diabetes

Type 2 diabetes (T2D) is associated with reduced gut microbiome diversity, although the cause is unclear. Metabolites generated by gut microbes also appear to be causative factors in T2D. We therefore searched for serum metabolites predictive of gut microbiome diversity in 1018 females from TwinsUK with concurrent metabolomic profiling and microbiome composition. We generated a Microbial Metabolites Diversity (MMD) score of six circulating metabolites that explained over 18% of the variance in microbiome alpha diversity. Moreover, the MMD score was associated with a significantly lower odds of prevalent (OR[95%CI] = 0.22[0.07;0.70], P = .01) and incident T2D (HR[95%CI] = 0.31[0.11,0.90], P = .03). We replicated our results in 1522 individuals from the ARIC study (prevalent T2D: OR[95%CI] = 0.79[0.64,0.96], P = .02, incident T2D: HR[95%CI] = 0.87[0.79,0.95], P = .003). The MMD score mediated 28%[15%,94%] of the total effect of gut microbiome on T2D after adjusting for confounders. Metabolites predicting higher microbiome diversity included 3-phenylpropionate(hydrocinnamate), indolepropionate, cinnamoylglycine and 5-alpha-pregnan-3beta,20 alpha-diol monosulfate(2) of which indolepropionate and phenylpropionate have already been linked to lower incidence of T2D. Metabolites correlating with lower microbial diversity included glutarate and imidazole propionate, of which the latter has been implicated in insulin resistance. Our results suggest that the effect of gut microbiome diversity on T2D is largely mediated by microbial metabolites, which might be modifiable by diet