Showing papers by "Gerardo Heiss published in 2018"
TL;DR: In this paper, the authors combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci associated with general cognitive function.
Abstract: General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
421 citations
01 Jan 2018
203 citations
TL;DR: Arterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition, including interactions by race, APOE ε4 status, and cognition.
Abstract: Objective Arterial stiffness has been associated with evidence of cerebral small vessel disease (cSVD) and fibrillar β-amyloid (Aβ) deposition in the brain. These complex relationships have not been examined in racially and cognitively diverse cohorts. Methods The Atherosclerosis Risk in Communities (ARIC)–Neurocognitive Study collected detailed cognitive testing for adjudication of dementia and mild cognitive impairment (MCI), brain MRI, and arterial stiffness by pulse wave velocity (PWV, carotid-femoral [cfPWV] and heart-carotid [hcPWV]). The ARIC-PET ancillary study added Aβ imaging using florbetapir ([ 18 F]-AV-45) to obtain standardized uptake volume ratios and defined global Aβ-positivity as standardized uptake volume ratio >1.2. One-SD increase in PWV was related to brain volume, MRI-defined cSVD (e.g., cerebral microbleeds and white matter hyperintensity), and cortical Aβ deposition adjusted for age, body mass index, sex, race, and APOE e4 status. We examined the cross-sectional relationships including interactions by race, APOE e4 status, and cognition. Results Among the 320 ARIC-PET participants (76 [5] years, 45% black, 27% MCI), greater central stiffness (hcPWV) was associated with greater Aβ deposition (odds ratio [OR] = 1.31, 95% confidence interval [CI] 1.01–1.71). Greater central stiffness (cfPWV) was significantly associated with having lower brain volumes in Alzheimer disease–susceptible regions (in mm 3 , β = −1.5 [0.7 SD], p = 0.03) and high white matter hyperintensity burden (OR = 1.6, 95% CI 1.2–2.1). Furthermore, cfPWV was associated with a higher odds of concomitant high white matter hyperintensity and Aβ-positive scans (OR = 1.4, 95% CI 1.1–2.1). These associations were strongest among individuals with MCI and did not differ by race or APOE e4 status. Conclusions Arterial stiffness, measured by PWV, is an emerging risk factor for dementia through its repeated relationships with cognition, cSVD, and Aβ deposition.
106 citations
TL;DR: The authors identify and prioritize genetic loci for cIMT and plaque by GWAS and colocalization approaches and further demonstrate genetic correlation with CHD and stroke.
Abstract: Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans.
96 citations
TL;DR: The aim was to examine associations between midlife cardiovascular health and 20‐year cognitive decline among blacks and whites and to assess the impact of smoking, diet, and physical activity on these associations.
Abstract: Introduction The aim was to examine associations between midlife cardiovascular health (CVH) and 20-year cognitive decline among blacks and whites. Methods Midlife CVH metrics (American Heart Association's Life's Simple 7) were calculated and examined in relation to midlife and 20-year change in cognitive function among 13,270 whites and blacks from the Atherosclerosis Risk in Communities Cohort Study. We used linear mixed models to estimate adjusted associations of midlife CVH with midlife cognitive status and change. Results Higher midlife (Life's Simple 7) scores and individual metrics, particularly blood pressure and glucose, were associated with better midlife cognition and reduced 20-year decline. Midlife CVH 20-year neuroprotection was more pronounced among whites than blacks. Discussion Better midlife CVH was associated with higher midlife and reduced decline in cognitive function 20 years later. However, the benefits of midlife CVH on cognition were stronger for whites than for blacks. Our findings suggest that improved midlife CVH may promote enduring cognitive health.
58 citations
TL;DR: OH assessed in midlife was independently associated with incident dementia and ischemic stroke and potential mechanisms for these associations are needed and possible applications for prevention.
Abstract: Objective To examine associations of orthostatic hypotension (OH) with dementia and long-term cognitive decline and to update previously published results in the same cohort for stroke with an additional 16 years of follow-up Methods We analyzed data from 11,709 participants without a history of coronary heart disease or stroke who attended the baseline examination (1987–1989) of the prospective Atherosclerosis Risk in Communities (ARIC) study OH was defined as a drop in systolic blood pressure (BP) of at least 20 mm Hg or a drop in diastolic BP of at least 10 mm Hg on standing Dementia was ascertained via examination, contact with participants or their proxy, or medical record surveillance Ischemic stroke was ascertained via cohort surveillance of hospitalizations, cohort follow-up, and linkage with registries Both outcomes were adjudicated Cognitive function was ascertained via 3 neuropsychological tests administered in 1990 to 1992 and 1996 to 1998 and a full battery of tests in 2011 to 2013 Scores were summarized and reported as SDs We used adjusted Cox regression and linear mixed models Results Over ≈25 years, 1,068 participants developed dementia and 842 had an ischemic stroke Compared to persons without OH at baseline, those with OH had a higher risk of dementia (hazard ratio [HR] 154, 95% confidence interval [CI] 120–197) and ischemic stroke (HR 208, 95% CI 165–262) Persons with OH had greater, although nonsignificant, cognitive decline over 20 years (SD 009, 95% CI −002 to 021) Conclusions OH assessed in midlife was independently associated with incident dementia and ischemic stroke Additional studies are needed to elucidate potential mechanisms for these associations and possible applications for prevention
57 citations
TL;DR: High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI, and the usefulness of cardiac markers to identify individuals at high risk of CLI is suggested.
Abstract: Aims: Cardiac troponin T (cTnT) is suggested as a predictor of amputation in patients with peripheral artery disease (PAD). However, cTnT-PAD association has not been systematically studied in a large study. This study evaluated the association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also explored whether natriuretic peptide (NT-proBNP), another representative cardiac marker, predicts PAD risk.
Methods and results: Among 12 288 middle-aged adults, the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss considered as critical limb ischaemia (CLI)]) were quantified with multivariable Cox regression models. The risk discrimination was assessed by c-statistic. During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases). In demographically adjusted models, the highest category of hs-cTnT (≥14 vs. <3 ng/L) and NT-proBNP (≥258.3 vs. <51.5 pg/mL) showed ∼8- and 10-20-fold higher risk of PAD and CLI, respectively. Even after adjusting for potential confounders and each other, hazard ratios were greater for CLI than for PAD (7.74 95% confidence interval [95% CI 4.43-13.55] vs. 2.84 [2.02-4.00] for the highest vs. reference hs-cTnT category and 4.63 [2.61-8.23] vs. 3.16 [2.23-4.49] for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI.
Conclusion: High-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.
46 citations
TL;DR: It is suggested that central arterial stiffness may be an important pathophysiologic phenotype of vascular disease in CKD and both lower eGFR and higher ACR are independently associated with measures of central arterIAL stiffness.
46 citations
TL;DR: Optimal Life's Simple 7 at middle age was associated with better prognosis after myocardial infarction in later life, suggesting a secondary prevention benefit of having better cardiovascular health status in midlife.
Abstract: Background The American Heart Association recommends focusing on 7 health factors (Life9s Simple 7) for primordial prevention of cardiovascular health. However, whether greater adherence to Life9s Simple 7 in midlife improves prognosis after myocardial infarction (MI) in later life is unknown. Methods and Results In 1277 participants who developed MI during the ARIC (Atherosclerosis Risk in Communities) Study follow‐up, a 14‐point score of Life9s Simple 7 was constructed according to the status (2 points for ideal, 1 point for intermediate, and 0 points for poor) of each of 7 factors (smoking, adiposity, physical activity, diet, total cholesterol, blood pressure, and fasting glucose) at baseline (1987–1989). Hazard ratios for composite and individual adverse outcomes of all‐cause mortality, cardiovascular mortality, recurrent MI, heart failure, and stroke were calculated according to Life9s Simple 7 score. During a median follow‐up of 3.3 years, 918 participants (72%) had subsequent adverse outcomes after MI. Life9s Simple 7 score at middle age was inversely associated with adverse outcomes after MI (adjusted hazard ratios of composite outcome, 0.57 [95% confidence interval, 0.39–0.84] if score is ≥10, 0.78 [95% confidence interval, 0.57–1.07] if score is 7–9, and 0.82 [95% confidence interval, 0.60–1.11] if score is 4–6 versus ≤3). The association was largely independent of access to care and MI severity. Individual factors related to better prognosis after MI were ideal nonsmoking, body mass index, blood pressure, and fasting glucose. Conclusions Optimal Life9s Simple 7 at middle age was associated with better prognosis after MI in later life. Our findings suggest a secondary prevention benefit of having better cardiovascular health status in midlife.
41 citations
TL;DR: Carvedilol initiation was associated with higher 1-year all-cause and cardiovascular mortality and one potential mechanism for these findings may be the increased occurrence of intradialytic hypotension after carvedilol (vs metoprolol) initiation.
37 citations
TL;DR: Maintaining an optimal weight, in addition to controlling other cardiovascular risk factors, may play a role in reducing risk of PAD with CLI after adjusting for potential confounders.
Abstract: Background We conducted an analysis of data from the ARIC (Atherosclerosis Risk in Communities) study to assess the independent association of obesity with peripheral artery disease (PAD) and criti...
University of North Carolina at Chapel Hill1, Vanderbilt University2, University of Minnesota3, Illumina4, Fred Hutchinson Cancer Research Center5, University of Southern California6, University of Washington7, Case Western Reserve University8, Cornell University9, Washington University in St. Louis10, Johns Hopkins University11, Icahn School of Medicine at Mount Sinai12, University of California, Irvine13, University of California, Los Angeles14, Mayo Clinic15, San Diego State University16, University of Illinois at Chicago17, Yeshiva University18, University of Iowa19, Rutgers University20, National Institutes of Health21
TL;DR: The findings support the transferability of reproductive trait loci discovered in European women to women of other race/ethnicities and indicate the presence of additional trans-ethnic associations both at both novel and established loci.
Abstract: Current knowledge of the genetic architecture of key reproductive events across the female life course is largely based on association studies of European descent women. The relevance of known loci for age at menarche (AAM) and age at natural menopause (ANM) in diverse populations remains unclear. We investigated 32 AAM and 14 ANM previously-identified loci and sought to identify novel loci in a trans-ethnic array-wide study of 196,483 SNPs on the MetaboChip (Illumina, Inc.). A total of 45,364 women of diverse ancestries (African, Hispanic/Latina, Asian American and American Indian/Alaskan Native) in the Population Architecture using Genomics and Epidemiology (PAGE) Study were included in cross-sectional analyses of AAM and ANM. Within each study we conducted a linear regression of SNP associations with self-reported or medical record-derived AAM or ANM (in years), adjusting for birth year, population stratification, and center/region, as appropriate, and meta-analyzed results across studies using multiple meta-analytic techniques. For both AAM and ANM, we observed more directionally consistent associations with the previously reported risk alleles than expected by chance (p-valuesbinomial≤0.01). Eight densely genotyped reproductive loci generalized significantly to at least one non-European population. We identified one trans-ethnic array-wide SNP association with AAM and two significant associations with ANM, which have not been described previously. Additionally, we observed evidence of independent secondary signals at three of six AAM trans-ethnic loci. Our findings support the transferability of reproductive trait loci discovered in European women to women of other race/ethnicities and indicate the presence of additional trans-ethnic associations both at both novel and established loci. These findings suggest the benefit of including diverse populations in future studies of the genetic architecture of female growth and development.
TL;DR: Higher physical activity in late-life, and habitual physical activity from mid-life to late- life, is associated with lower central arterial stiffness and pressure pulsatility in a large population-based sample of community-dwelling older adults.
Abstract: INTRODUCTION Regular physical activity appears to attenuate or even reverse age-related arterial stiffening. Yet, it is not clear if the reduced stiffening associated with habitual physical activity is also observed in community-dwelling older adults. METHODS Among 3893 older adults in a prospective cohort study, we associated physical activity with measures of central arterial stiffness (via carotid-femoral pulse wave velocity or cfPWV) and pressure pulsatility (via central pulse pressure or cPP). We also examined the association of long-term habitual physical activity, measured as persistence in physical activity levels from mid-life to late-life, with cfPWV and cPP among 1747 participants. RESULTS The adjusted mean difference in cfPWV was lower, reflecting less arterial stiffness, for those with moderate (s = -0.30 m/s) or high (s = -0.38 m/s) physical activity compared with no physical activity. The adjusted mean difference in cPP was also lower for those with high (s = -2.49 mmHg) physical activity, relative to no physical activity. Stronger effect estimates were observed among those with persistent physical activity from mid-life to late-life. CONCLUSION Higher physical activity in late-life, and habitual physical activity from mid-life to late-life, is associated with lower central arterial stiffness and pressure pulsatility in a large population-based sample of community-dwelling older adults.
TL;DR: This study provides important data estimating frequency of care and mortality by the setting of initial PAD diagnosis among those diagnosed in outpatient and inpatient settings, respectively.
Abstract: Background Available health services data for individuals with peripheral artery disease (PAD) are often from studies of those eligible for or undergoing intervention. Knowledge of the frequency of care and mortality following an initial PAD diagnosis by setting (outpatient versus inpatient) is limited and represents an opportunity to provide new benchmark information. Methods and Results The purpose of this study was to characterize the frequency of care and mortality following an incident PAD diagnosis in the outpatient or inpatient setting using data from the ARIC (Atherosclerosis Risk in Communities) study cohort linked with Centers for Medicare and Medicaid Services fee‐for‐service claims data (2002–2012). Direct standardization was used to estimate age‐standardized rates of encounters and mortality. PAD was defined by billing code in any claim position. We observed 1086 incident PAD cases (873 outpatient, 213 inpatient). At 1 year after diagnosis, participants diagnosed in the outpatient setting had 2.15 (95% confidence interval [CI], 2.10–2.21) PAD‐related outpatient encounters per person‐year, and 6.4% (95% CI, 4.8–8.1) had a PAD‐related hospitalization. Conversely, participants diagnosed in the inpatient setting had 1.02 (95% CI, 0.94–1.10) PAD‐related outpatient encounters per person‐year, and 14.2% (95% CI, 9.3–18.7) had a PAD‐related rehospitalization. One‐year mortality was 7.1% (95% CI, 5.4–8.7) and 16.0% (95% CI, 11.0–21.1) among those diagnosed in outpatient and inpatient settings, respectively. Conclusions This study provides important data estimating frequency of care and mortality by the setting of initial PAD diagnosis. Individuals with PAD are frequent users of health care, and those diagnosed in the inpatient setting have high rates of rehospitalization and mortality.
TL;DR: GDM is associated with the subsequent development of albuminuria among black women in CARDIA, and there was evidence of a GDM-race interaction on CKD risk.
TL;DR: Greater visit‐to‐visit SBP or DBP variability from midlife on is modestly associated with lower cognitive function, whereas higher mean SBP and lower DBP levels from mid life to later life are modestlyassociated with cognitive decline in later life.
Abstract: Background To understand how blood pressure (BP) from midlife and beyond is related to cognition in older age, a lifespan approach is needed. We assessed the associations of BP levels and variabili...
TL;DR: This work tested the hypothesis that poor sense of smell is associated with lower cognitive function and higher mild cognitive impairment (MCI) prevalence and found it to be true.
Abstract: Introduction We tested the hypothesis that poor sense of smell is associated with lower cognitive function and higher mild cognitive impairment (MCI) prevalence. Methods Olfaction, measured by the Sniffin' Sticks test, was categorized as olfactory impairment (OI) (score ≤6) or no OI (score >6). MCI was adjudicated based on review of a neuropsychological examination. Linear regression estimated the mean difference in cognitive factor scores, and log-binomial regression quantified MCI prevalence among participants with versus without OI. Results Participants with OI had lower mean factor scores (memory: −0.27 standard deviation [SD], 95% confidence interval [CI]: −0.35 to −0.19; language: −0.24 SD, 95% CI: −0.30 to −0.17; executive function/processing speed: −0.09 SD, 95% CI: −0.12 to −0.06; and general cognitive performance: −0.25 SD, 95% CI: −0.30 to −0.20). OI was also associated with MCI (n = 204; prevalence ratio = 1.56, 95% CI: 1.37, 1.78). Discussion An impaired sense of smell may serve as a readily accessible early marker of neurodegeneration and improve upon the prevailing delayed diagnoses and underascertainment of MCI/dementia.
TL;DR: Nontraditional glycemic markers were associated with incident PAD independent of fasting glucose but not necessarily HbA1c, and these results support the importance of glucose metabolism in the progression to CLI.
TL;DR: Previously reported associations between periodontitis and NAFLD were marginal to null in this study of a diverse group of Hispanics/Latinos.
Abstract: BACKGROUND Non-alcoholic fatty liver disease (NAFLD) prevalence is greater among Hispanics/Latinos than other racial/ethnic groups and prevalence is further reported to vary among Hispanic/Latino background groups. Experimental animal and human studies demonstrate associations between periodontitis and NAFLD, not yet reported among Hispanics/Latinos. This study examined periodontitis as a novel risk factor that may contribute to the burden of NAFLD among Hispanics/Latinos. METHODS Data came from 11,914 participants of the Hispanic Community Health Study/Study of Latinos. Periodontitis was defined as the extent (none, 40 IU/L or aspartate aminotransferase (AST) > 37 IU/L for men and ALT > 31 IU/L or AST > 31 IU/L for women. Survey-logistic regression models estimated prevalence odds ratios (POR) and 95% confidence intervals (CI) for the association between periodontitis and suspected NAFLD. RESULTS The overall age-standardized percentage of study participants with < 30% of sites with CAL ≥3 mm or PD ≥4 mm was 53.5% and 58.6%, respectively, while participants with ≥30% sites with CAL ≥3 mm or PD ≥4 mm comprised 16% and 5.72%, respectively. The overall age-standardized prevalence (95% CI) of suspected NAFLD was 18.1% (17.1-19.0). For the entire cohort, we observed a dose-response (i.e. graded) association between PD ≥4 mm and the prevalence odds of suspected NAFLD, whereby participants with < 30% affected had a crude POR = 1.19 (95% CI: 1.03, 1.38) while participants with ≥30% affected had a crude POR = 1.39 (95% CI: 1.02, 1.90). These crude estimates were attenuated toward the null and rendered non-significant upon covariate adjustment. No differences were found by Hispanic/Latino background group. CONCLUSION Previously reported associations between periodontitis and NAFLD were marginal to null in this study of a diverse group of Hispanics/Latinos.
Fred Hutchinson Cancer Research Center1, University of Washington2, University of Texas Health Science Center at Houston3, University of North Carolina at Chapel Hill4, PATH5, Baylor College of Medicine6, University of San Diego7, Stanford University8, University of Minnesota9, Vanderbilt University Medical Center10, University of Alabama at Birmingham11, San Diego State University12, University of Illinois at Chicago13, Northwestern University14, Anschutz Medical Campus15, University of Southern California16, University of California, San Francisco17, Case Western Reserve University18, University of Hawaii19
TL;DR: This study identified novel variants and loci associated with CRP levels, generalized known CRP associations to a multiethnic study population, refined association signals atSeveral loci and found evidence for multiple independent signals at several well-known loci.
Abstract: C-reactive protein (CRP) is a circulating biomarker indicative of systemic inflammation. We aimed to evaluate genetic associations with CRP levels among non-European-ancestry populations through discovery, fine-mapping and conditional analyses. A total of 30 503 non-European-ancestry participants from 6 studies participating in the Population Architecture using Genomics and Epidemiology study had serum high-sensitivity CRP measurements and ∼200 000 single nucleotide polymorphisms (SNPs) genotyped on the Metabochip. We evaluated the association between each SNP and log-transformed CRP levels using multivariate linear regression, with additive genetic models adjusted for age, sex, the first four principal components of genetic ancestry, and study-specific factors. Differential linkage disequilibrium patterns between race/ethnicity groups were used to fine-map regions associated with CRP levels. Conditional analyses evaluated for multiple independent signals within genetic regions. One hundred and sixty-three unique variants in 12 loci in overall or race/ethnicity-stratified Metabochip-wide scans reached a Bonferroni-corrected P-value <2.5E-7. Three loci have no (HACL1, OLFML2B) or only limited (PLA2G6) previous associations with CRP levels. Six loci had different top hits in race/ethnicity-specific versus overall analyses. Fine-mapping refined the signal in six loci, particularly in HNF1A. Conditional analyses provided evidence for secondary signals in LEPR, IL1RN and HNF1A, and for multiple independent signals in CRP and APOE. We identified novel variants and loci associated with CRP levels, generalized known CRP associations to a multiethnic study population, refined association signals at several loci and found evidence for multiple independent signals at several well-known loci. This study demonstrates the benefit of conducting inclusive genetic association studies in large multiethnic populations.
TL;DR: Consideration of outpatient HF is warranted to better understand the burden of HF and its temporal trends, as the overall incidence of HF decreased from 2008 to 2014, regardless of health-care setting.
Abstract: Reports on the burden of heart failure (HF) have largely omitted HF diagnosed in outpatient settings. We quantified annual incidence rates ([IR] per 1,000 person years) of HF identified in ambulatory clinics, emergency departments (EDs), and during hospital stays in a national probability sample of Medicare beneficiaries from 2008 to 2014, by age and race/ethnicity. A 20% random sample of Medicare beneficiaries ages ≥65 years with continuous Medicare Parts A, B, and D coverage was used to estimate annual IRs of HF identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Of the 681,487 beneficiaries with incident HF from 2008 to 2014, 283,451 (41%) presented in ambulatory clinics, 76,919 (11%) in EDs, and 321,117 (47%) in hospitals. Overall, incidence of HF in ambulatory clinics decreased from 2008 (IR 22.2, 95% confidence interval [CI] 22.0, 22.4) to 2014 (IR 15.0, 95% CI 14.8, 15.1). Similarly, incidence of HF-related ED visits without an admission to the hospital decreased somewhat from 2008 (IR 5.5, 95% CI 5.4, 5.6) to 2012 (IR 4.2, 95% CI 4.1, 4.3) and stabilized from 2013 to 2014. Similar to previous reports, HF hospitalizations, both International Classification of Diseases, Ninth Revision, Clinical Modification code 428.x in the primary and any position, decreased over the study period. More than half of all new cases of HF in Medicare beneficiaries presented in an ambulatory clinic or ED. The overall incidence of HF decreased from 2008 to 2014, regardless of health-care setting. In conclusion, consideration of outpatient HF is warranted to better understand the burden of HF and its temporal trends.
TL;DR: Better cardiovascular health, as defined by higher Life's Simple 7 score, is associated with a substantially lower risk of peripheral artery disease.
TL;DR: The results highlight the role of area-level social determinants of health in the incidence of HF in both the IP and OP settings and may have implications for HF prevention policies.
TL;DR: 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.
Abstract: 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.
TL;DR: The REasons for Geographic and Racial Differences in Stroke-Severe Sepsis Risk Score (REGARDS-SSRS) may potentially play a role in identifying community-dwelling adults at high severe sepsis risk.
Abstract: There are no validated systems for characterizing long-term risk of severe sepsis in community-dwelling adults. We tested the ability of the REasons for Geographic and Racial Differences in Stroke-Severe Sepsis Risk Score (REGARDS-SSRS) to predict 10-year severe sepsis risk in separate cohorts of community-dwelling adults. We internally tested the REGARDS-SSRS on the REGARDS-Medicare subcohort. We then externally validated the REGARDS-SSRS using (1) the Cardiovascular Health Study (CHS) and (2) the Atherosclerosis Risk in Communities (ARIC) cohorts. Participants included community-dwelling adults: REGARDS-Medicare, age ≥65 years, n = 9522; CHS, age ≥65 years, n = 5888; ARIC, age 45⁻64 years, n = 11,584. The primary exposure was 10-year severe sepsis risk, predicted by the REGARDS-SSRS from participant sociodemographics, health behaviors, chronic medical conditions and select biomarkers. The primary outcome was first severe sepsis hospitalizations, defined as the concurrent presence of ICD-9 discharge diagnoses for a serious infection and organ dysfunction. Median SSRS in the cohorts were: REGARDS-Medicare 11 points (IQR 7⁻16), CHS 10 (IQR 6⁻15), ARIC 7 (IQR 5⁻10). Severe sepsis incidence rates were: REGARDS-Medicare 30.7 per 1000 person-years (95% CI: 29.2⁻32.2); CHS 11.9 (10.9⁻12.9); ARIC 6.8 (6.3⁻7.3). SSRS discrimination for first severe sepsis events were: REGARDS-Medicare C-statistic 0.704 (95% CI: 0.691⁻0.718), CHS 0.696 (0.675⁻0.716), ARIC 0.697 (0.677⁻0.716). The REGARDS-SRSS may potentially play a role in identifying community-dwelling adults at high severe sepsis risk.
TL;DR: In US Hispanic/Latinos, sleep-disordered breathing was independently associated with higher odds of prevalent albuminuria, and this association varied by Hispanic/Latino background group.
TL;DR: Modifiable linear regression characterized the impact on incident CKD of two approaches for blood pressure management and found Modest population‐wide reductions in systolic BP hold potential for the primary prevention of CKD.
Abstract: While much of the chronic kidney disease (CKD) literature focuses on the role of blood pressure reduction in delaying CKD progression, little is known about the benefits of modest population-wide decrements in blood pressure on incident CKD. The authors used multivariable linear regression to characterize the impact on incident CKD of two approaches for blood pressure management: (1) a 1-mm Hg reduction in systolic BP across the entire study population; and (2) a 10% reduction in participants with unaware, untreated, and uncontrolled BP above goal as defined by the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) thresholds. Over a mean of 20 years of follow-up (ARIC [Atherosclerosis Risk in Communities] study, n = 15 390), 3852 incident CKD events were ascertained. After adjustment, a 1-mm Hg decrement in systolic BP across the population was associated with an estimated 11.7 (95% confidence interval [CI], 6.2-17.3) and 13.4 (95% CI, 10.3-16.6) fewer CKD events per 100 000 person-years in blacks and whites, respectively. Among participants with BP above JNC 7 goal, a 10% decrease in unaware, untreated, or uncontrolled BP was associated with 3.2 (95% CI, 2.0-4.9), 2.8 (95% CI, 1.8-4.3), and 5.8 (95% CI, 3.6-8.8) fewer CKD events per 100 000 person-years in blacks and 3.1 (95% CI, 2.3-4.1), 0.7 (95% CI, 0.5-0.9), and 1.0 (95% CI, 1.3-2.4) fewer CKD events per 100 000 person-years in whites. Modest population-wide reductions in systolic BP hold potential for the primary prevention of CKD.