Association of insulin resistance, from mid-life to late-life, with aortic stiffness in late-life: the Atherosclerosis Risk in Communities Study.

BACKGROUND: Insulin resistance may contribute to aortic stiffening that leads to end-organ damage. We examined the cross-sectional association and prospective association of insulin resistance and aortic stiffness in older adults without diabetes. METHODS: We analyzed 2571 men and women at Visit 5 (in 2011-2013), and 2350 men and women at repeat examinations from baseline at Visit 1 (in 1987-1989) to Visit 5 (in 2011-2013). Linear regression was used to estimate the difference in aortic stiffness per standard unit of HOMA-IR, TG/HDL-C, and TyG at Visit 5. Linear mixed effects were used to assess if high, as opposed to non-high, aortic stiffness (> 75th percentile) was preceded by a faster annual rate of change in log-HOMA-IR, log-TG/HDL-C, and log-TyG from Visit 1 to Visit 5. RESULTS: The mean age of participants was 75 years, 37% (n = 957) were men, and 17% (n = 433) were African American. At Visit 5, higher HOMA-IR, higher TG/HDL-C, and higher TyG were associated with higher aortic stiffness (16 cm/s per SD (95% CI 6, 27), 29 cm/s per SD (95% CI 18, 40), and 32 cm/s per SD (95% CI 22, 42), respectively). From Visit 1 to Visit 5, high aortic stiffness, compared to non-high aortic stiffness, was not preceded by a faster annual rate of change in log-HOMA-IR from baseline to 9 years (0.030 (95% CI 0.024, 0.035) vs. 0.025 (95% CI 0.021, 0.028); p = 0.15) or 9 years onward (0.011 (95% CI 0.007, 0.015) vs. 0.011 (95% CI 0.009, 0.013); p = 0.31); in log-TG/HDL-C from baseline to 9 years (0.019 (95% CI 0.015, 0.024) vs. 0.024 (95% CI 0.022, 0.026); p = 0.06) or 9 years onward (- 0.007 (95% CI - 0.010, - 0.005) vs. - 0.009 (95% CI - 0.010, - 0.007); p = 0.08); or in log-TyG from baseline to 9 years (0.002 (95% CI 0.002, 0.003) vs. 0.003 (95% CI 0.003, 0.003); p = 0.03) or 9 years onward (0 (95% CI 0, 0) vs. 0 (95% CI 0, 0); p = 0.08). CONCLUSIONS: Among older adults without diabetes, insulin resistance was associated with aortic stiffness, but the putative role of insulin resistance in aortic stiffness over the life course requires further study.

Insulin resistance and reduced cardiac autonomic function in older adults: the Atherosclerosis Risk in Communities study.

BACKGROUND: Prior studies have shown insulin resistance is associated with reduced cardiac autonomic function measured at rest, but few studies have determined whether insulin resistance is associated with reduced cardiac autonomic function measured during daily activities. METHODS: We examined older adults without diabetes with 48-h ambulatory electrocardiography (n = 759) in an ancillary study of the Atherosclerosis Risk in Communities Study. Insulin resistance, the exposure, was defined by quartiles for three indexes: 1) the homeostatic model assessment of insulin resistance (HOMA-IR), 2) the triglyceride and glucose index (TyG), and 3) the triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C). Low heart rate variability, the outcome, was defined by <25th percentile for four measures: 1) standard deviation of normal-to-normal R-R intervals (SDNN), a measure of total variability; 2) root mean square of successive differences in normal-to-normal R-R intervals (RMSSD), a measure of vagal activity; 3) low frequency spectral component (LF), a measure of sympathetic and vagal activity; and 4) high frequency spectral component (HF), a measure of vagal activity. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals weighted for sampling/non-response, adjusted for age at ancillary visit, sex, and race/study-site. Insulin resistance quartiles 4, 3, and 2 were compared to quartile 1; high indexes refer to quartile 4 versus quartile 1. RESULTS: The average age was 78 years, 66% (n = 497) were women, and 58% (n = 438) were African American. Estimates of association were not robust at all levels of HOMA-IR, TyG, and TG/HDL-C, but suggest that high indexes were associated consistently with indicators of vagal activity. High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low RMSSD (OR: 1.68 (1.00, 2.81), OR: 2.03 (1.21, 3.39), and OR: 1.73 (1.01, 2.91), respectively). High HOMA-IR, high TyG, and high TG/HDL-C were consistently associated with low HF (OR: 1.90 (1.14, 3.18), OR: 1.98 (1.21, 3.25), and OR: 1.76 (1.07, 2.90), respectively). CONCLUSIONS: In older adults without diabetes, insulin resistance was associated with reduced cardiac autonomic function - specifically and consistently for indicators of vagal activity - measured during daily activities. Primary prevention of insulin resistance may reduce the related risk of cardiac autonomic dysfunction.

The prevalence of atrial fibrillation on 48-hour ambulatory electrocardiography in African Americans compared to Whites: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND: A lower prevalence of atrial fibrillation (AF), but paradoxically higher burden of cardiovascular disease risk factors, has been observed among African Americans compared to Whites in studies of AF identified by mostly 12-lead electrocardiograms (ECGs) and clinically. METHODS: We performed 48-hour ambulatory electrocardiography (aECG) in a biracial sample of 1,193 participants in the Atherosclerosis Risk in Communities (ARIC) (mean age = 78 years, 62% African Americans, 64% female). Atrial fibrillation was identified from aECG, study visit ECGs, and discharge codes from cohort hospitalizations. We used covariate-adjusted logistic regression to estimate prevalence odds ratios (ORs) for AF in African Americans versus Whites, with adjustment for sampling and nonresponse. RESULTS: African Americans were more likely than Whites to have hypertension and diabetes but less likely to have coronary heart disease. The prevalence of AF detected by aECG or ARIC study ECG (adjusted for age and coronary heart disease) was lower in African Americans than Whites (2.7% vs 5.0%). White men had a higher (although not significant) AF prevalence of 7.8% compared to the other race and gender groups at 2.3%-2.8%. The adjusted OR for AF was 0.49 (0.24-0.99) comparing African Americans to Whites. Findings were similar when AF was defined to include prior AF hospitalizations (OR = 0.42, 0.25-0.72). There were no significant differences by race for asymptomatic or paroxysmal AF. CONCLUSIONS: Atrial fibrillation was less prevalent in African American than white older adults, regardless of detection method. Although overall detection of new AF cases with aECG was low, future studies should consider longer-term monitoring to characterize AF by race.

Repeatability of ectopic beats from 48-hr ambulatory electrocardiography: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: The purpose of this study was to characterize the repeatability of ectopic beats, defined by premature atrial contractions (PACs) and premature ventricular contractions (PVCs), on ambulatory electrocardiogram (aECG) monitoring and evaluate the effect of length of aECG monitoring on the repeatability estimates. METHODS: This analysis includes 95 randomly selected participants from the Atherosclerosis Risk in Communities Study (ARIC; 2011-2013). The participants wore a Holter monitor for two, 48-hr periods separated by a mean of 38 days following an identical, standardized protocol. We divided each 48-hr recording into 3-, 6-, 12-, and 24-hr recording periods and calculated intraclass correlation coefficients (ICCs) for PACs and PVCs and also as a percentage of the corresponding total of recorded beats per hour among these periods. RESULTS: All participants had ≥1 PAC during the 48-hr recordings, and only two participants had no PVCs. ICCs were >0.83 for all indices and recording lengths ≥12 hrs. ICCs were intermediate for 6-hr recordings (range 0.80-0.83) and lower for 3-hr recordings (range 0.74-0.80). The ratio of the between- to within-participant variation increased with recording length. CONCLUSION: Repeatability of PACs and PVCs was excellent for recording lengths of 6-24 hr and fair for 3 hr. Repeatability varies over shorter duration recordings within the 48-hr recording period, and thus the present results have implications for detection algorithms for ectopic beats and can facilitate epidemiologic and clinical applications in which knowledge of measurement variability and misclassification are needed.

Higher Mortality in registrants with sudden model for end-stage liver disease increase: Disadvantaged by the current allocation policy.

Liver allocation is based on current Model for End-Stage Liver Disease (MELD) scores, with priority in the case of a tie being given to those waiting the longest with a given MELD score. We hypothesized that this priority might not reflect risk: registrants whose MELD score has recently increased receive lower priority but might have higher wait-list mortality. We studied wait-list and posttransplant mortality in 69,643 adult registrants from 2002 to 2013. By likelihood maximization, we empirically defined a MELD spike as a MELD increase ≥ 30% over the previous 7 days. At any given time, only 0.6% of wait-list patients experienced a spike; however, these patients accounted for 25% of all wait-list deaths. Registrants who reached a given MELD score after a spike had higher wait-list mortality in the ensuing 7 days than those with the same resulting MELD score who did not spike, but they had no difference in posttransplant mortality. The spike-associated wait-list mortality increase was highest for registrants with medium MELD scores: specifically, 2.3-fold higher (spike versus no spike) for a MELD score of 10, 4.0-fold higher for a MELD score of 20, and 2.5-fold higher for a MELD score of 30. A model incorporating the MELD score and spikes predicted wait-list mortality risk much better than a model incorporating only the MELD score. Registrants with a sudden MELD increase have a higher risk of short-term wait-list mortality than is indicated by their current MELD score but have no increased risk of posttransplant mortality; allocation policy should be adjusted accordingly.

Short-Term Repeatability of Insulin Resistance Indexes in Older Adults: The Atherosclerosis Risk in Communities Study.

Context: The homeostatic model assessment of insulin resistance (HOMA-IR) and triglyceride (TG)/high-density lipoprotein cholesterol (HDL-C) ratio (TG/HDL-C) are insulin resistance indexes routinely used in clinical and population-based studies; however, their short-term repeatability is not well characterized. Objective: To quantify the short-term repeatability of insulin resistance indexes and their analytes, consisting of fasting glucose and insulin for HOMA-IR and TG and HDL-C for TG/HDL-C. Design: Prospective cohort study. Participants: A total of 102 adults 68 to 88 years old without diabetes attended an initial examination and repeated examination (mean, 46 days; range, 28 to 102 days). Blood samples were collected, processed, shipped, and assayed following a standardized protocol. Main Outcome Measures: Repeatability was quantified using the intraclass correlation coefficient (ICC) and within-person coefficient of variation (CV). Minimum detectable change (MDC95) and minimum detectable difference with 95% confidence (MDD95) were quantified. Results: For HOMA-IR, insulin, and fasting glucose, the ICCs were 0.70, 0.68, and 0.70, respectively; their respective within-person CVs were 30.4%, 28.8%, and 5.6%. For TG/HDL-C, TG, and HDL-C, the ICCs were 0.80, 0.68, and 0.91, respectively; their respective within-person CVs were 23.0%, 20.6%, and 8.2%. The MDC95 was 2.3 for HOMA-IR and 1.4 for TG/HDL-C. The MDD95 for a sample of n = 100 was 0.8 for HOMA-IR and 0.6 for TG/HDL-C. Conclusions: Short-term repeatability was fair to good for HOMA-IR and excellent for TG/HDL-C according to suggested benchmarks, reflecting the short-term variability of their analytes. These measurement properties can inform the use of these indexes in clinical and population-based studies.

Repeatability of Central and Peripheral Pulse Wave Velocity Measures: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Arterial stiffness measures are emerging tools for risk assessment and stratification for hypertension and cardiovascular disease (CVD). Carotid-femoral pulse wave velocity (cfPWV) is an established measure of central arterial stiffness. Other measures of PWV include femoral-ankle (faPWV), a measure of peripheral stiffness, and brachial-ankle PWV (baPWV), a composite measure of central and peripheral stiffness. Repeatability of central, peripheral, and composite PWV measures has not been adequately examined or compared. METHODS: Participants (n = 79; mean age 75.7 years; USA) from a repeatability study nested within the Atherosclerosis Risk in Communities (ARIC) Study visit 5 (2011-2013) underwent 2 standardized visits, 4-8 weeks apart. Trained technicians obtained 2 PWV measurements at each visit using the VP-1000 Plus system. We calculated the intraclass correlation coefficient (ICC), SE of measurement, and minimal detectable change (MDC95; 95% confidence interval) and difference (MDD). RESULTS: The ICCs and 95% confidence intervals (95% CIs) were 0.70 (0.59, 0.81) for cfPWV, 0.84 (0.78, 0.90) for baPWV, and 0.69 (0.59, 0.79) for faPWV. The MDC95 between repeat measures within an individual was 411.0 cm/s for cfPWV, 370.6 cm/s for baPWV, and 301.4 cm/s for faPWV. The MDD for 2 independent samples of 100 per group was 139.3 cm/s for cfPWV, 172.3 cm/s for baPWV, and 100.4 cm/s for faPWV. CONCLUSIONS: Repeatability was acceptable for all PWV measures in a multicenter, population-based study of older adults and supports its use in epidemiologic studies. Quantifying PWV measurement variation is critical for applications to risk assessment and stratification and eventual translation to clinical practice.

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

BACKGROUND: 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. METHODS: Cohort members attending the 5th exam (2011-2013) of the Atherosclerosis Risk in Communities (ARIC) study had pulse wave velocity (PWV) measures performed at the carotid-femoral (cfPWV), brachial-ankle (baPWV), and femoral-ankle (faPWV) segments. Fasting glucose ≥126mg/dl, glycated hemoglobin (HbA1c) ≥6.5%, or currently taking diabetes medication defined diabetes. Fasting glucose 100-125mg/dl or HbA1c 5.7%-6.4% among those without diabetes defined prediabetes. Cross-sectional associations were modeled using multivariable linear regression. RESULTS: Among 4,279 eligible participants with cfPWV measures (mean age 75 years), 22% were African-American, 25.5% had diabetes, and 54.7% had prediabetes. Compared to those with normal glucose, cfPWV was 95.8cm/s higher (stiffer) on average for those with diabetes (for reference: being 1 year older was associated with 14.4cm/s higher cfPWV). Similar findings were seen for diabetes and baPWV, although attenuated. Interestingly, faPWV was 17.6cm/s lower for those with diabetes compared to normal glucose. There was a significant positive association between baPWV and prediabetes. Among those with diabetes, cfPWV was higher for those with albuminuria, reduced kidney function, duration of diabetes ≥10 years, and elevated HbA1c (HbA1c ≥7). CONCLUSION: Among older adults, diabetes is associated with higher central arterial stiffness and lower peripheral arterial stiffness, and prediabetes is associated with higher baPWV. Cross-sectionally, the magnitude of the effect of diabetes on central stiffness is equivalent to 6 years of arterial aging.

Comparative associations of diabetes risk factors with five measures of hyperglycemia.

OBJECTIVE: To compare the associations of diabetes mellitus risk factors with nontraditional markers of hyperglycemia (glycated albumin, fructosamine, 1,5-anhydroglucitol (1,5-AG)) to those observed with traditional markers (fasting glucose, hemoglobin A1c (HbA1c)). DESIGN: Cross-sectional study. SETTING: The community-based Atherosclerosis Risk in Communities (ARIC) Study cohort. PARTICIPANTS: A subsample of 1764 participants (309 with diagnosed diabetes and 1455 without diagnosed diabetes) from the ARIC Study who attended a clinic visit in 2005-2006. MAIN OUTCOME MEASURES: Elevated levels of glycated albumin, fructosamine, 1,5-AG, fasting glucose, and HbA1c in persons with and without a diagnosis of diabetes. RESULTS: The mean age of participants was 70 years (SD, 6), 43% were men, and 20% were African-American. Black race and family history of diabetes were generally positively associated with elevated levels of all biomarkers of hyperglycemia except 1,5-AG, which showed inverse but weaker associations with the risk factors examined. In general, patterns of risk factor associations observed for fasting glucose and HbA1c were similar to those observed for the nontraditional biomarkers of hyperglycemia but with one clear exception: body mass index (BMI). In persons without a diagnosis of diabetes, BMI was positively associated with fasting glucose and HbA1c, but the associations of BMI with glycated albumin and fructosamine were inverse, with high values of these markers at low levels of BMI. 1,5-AG, which is lowered in the setting of hyperglycemia, was positively associated with BMI. CONCLUSIONS: Traditional diabetes risk factors have similar associations with glycated albumin and fructosamine as those for fasting glucose and HbA1c, with the exception of BMI. Risk factor associations with 1,5-AG were mostly inverse. The inverse associations of BMI with glycated albumin and fructosamine, and positive associations with 1,5-AG, may reflect pathways independent of glucose metabolism and merit further examination.

Maternal Dietary Patterns during Third Trimester in Association with Birthweight Characteristics and Early Infant Growth.

Our analysis examined the impact of maternal dietary patterns and lifestyle factors on markers of fetal growth, specifically birthweight and size for gestational age (small- (SGA) or large-for-gestational age (LGA)). The Infant Feeding Practices Study II, a prospective cohort study, surveyed pregnant women during their 3rd trimester, of which a subgroup (n = 893) completed a food frequency questionnaire. Maternal dietary patterns were evaluated by diet scores (Alternative Healthy Eating Index for Pregnancy and alternate Mediterranean diet) and by carbohydrate quality (glycemic index and glycemic load). Poisson regression with robust standard errors was used to examine the relative risk of SGA and separately LGA, with dietary patterns and other lifestyle factors. Linear regression was used to determine the association of birthweight and early infant growth with better dietary patterns. Relative risk of SGA and LGA was not associated with dietary patterns. Birthweight and infant growth were not associated with maternal diet. Smoking, however, increased the risk of delivering an SGA infant (RR = 2.92, 95% CI: 1.58-5.39), while higher prepregnancy BMI increased the risk of delivering an LGA infant (RR = 1.06, 95% CI: 1.03-1.09). Future studies are needed to evaluate whether deficiencies in more specific maternal dietary nutrients play a role in fetal growth.

Dietary patterns in association with postpartum weight retention.

BACKGROUND: Postpartum weight retention (PPWR) can contribute to obesity development in women of reproductive age. Few studies have examined the association between postnatal diet and PPWR. OBJECTIVE: We examined both PPWR and substantial PPWR (≥4.55 kg) in association with the following dietary patterns: the alternate Mediterranean Diet Score (aMED) and the Alternative Healthy Eating Index-2010 (AHEI-2010). DESIGN: Women (n = 1136) in the Infant Feeding Practices Study II (2005-2007) self-reported their prepregnancy and postpartum weights at ~4, 7, 10, and 14 mo. Dietary patterns were calculated from a food-frequency questionnaire administered ~4 mo postpartum. Linear mixed models and generalized estimating equations for repeated measurements were used to examine PPWR and substantial PPWR, respectively, in association with the dietary patterns with adjustment for energy intake, breastfeeding, age, education, smoking, and marital status. RESULTS: At 14 mo postpartum, the mean (±SD) PPWR was 1.1 ± 6.7 kg, and 22.4% of women had substantial PPWR. Although the change in PPWR over time seemed to differ by diet quality 4-7 mo postpartum, no differences were ultimately observed in the total mean PPWR or probability of substantial PPWR across aMED and AHEI-2010 categories during the rest of the follow-up (P > 0.12). Instead, PPWR and substantial PPWR were associated with total energy intake (at ~7-14 mo postpartum: 0.97 kg/1000 kcal (95% CI: 0.40, 1.55 kg/1000 kcal); OR: 1.25/1000 kcal (95% CI: 1.03, 1.52/1000 kcal), respectively]. CONCLUSIONS: Postpartum diet quality assessed by 2 patterns was not associated with weight retention. Total energy intake, regardless of the diet composition, plays a more important role in weight retention.