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1.
Transplantation ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31568217

RESUMO

BACKGROUND: Hepatitis C virus-positive (HCV+) kidney transplant (KT) recipients are at increased risks of rejection and graft failure. The optimal induction agent for this population remains controversial, particularly regarding concerns that anti-thymocyte globulin (ATG) might increase HCV-related complications. METHODS: Using SRTR and Medicare claims data, we studied 6780 HCV+ and 139,681 HCV- KT recipients in 1999-2016 who received ATG or interleukin-2 receptor antagonist (IL2RA) for induction. We first examined the association of recipient HCV status with receiving ATG (vs. IL2RA) using multilevel logistic regression. Then, we studied the association of ATG (vs. IL2RA) with KT outcomes (rejection, graft failure, and death) and hepatic complications (liver transplant registration and cirrhosis) among HCV+ recipients using logistic and Cox regression. RESULTS: HCV+ recipients were less likely to receive ATG than HCV- recipients (living donor, aOR=0.640.770.91; deceased donor, aOR=0.710.810.92). In contrast, HCV+ recipients who received ATG were at lower risk of acute rejection compared to those who received IL2RA (1-year crude incidence=11.6% vs. 12.6%; aOR=0.680.820.99). There was no significant difference in the risks of graft failure (aHR=0.861.001.17), death (aHR=0.850.951.07), liver transplant registration (aHR=0.580.971.61), and cirrhosis (aHR=0.730.921.16). CONCLUSIONS: Our findings suggest that ATG, as compared to IL2RA, may lower the risk of acute rejection without increasing hepatic complications in HCV+ KT recipients. Given the higher rates of acute rejection in this population, ATG appears to be safe and reasonable for HCV+ recipients.

3.
Nat Genet ; 2019 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-31578528

RESUMO

Elevated serum urate levels cause gout and correlate with cardiometabolic diseases via poorly understood mechanisms. We performed a trans-ancestry genome-wide association study of serum urate in 457,690 individuals, identifying 183 loci (147 previously unknown) that improve the prediction of gout in an independent cohort of 334,880 individuals. Serum urate showed significant genetic correlations with many cardiometabolic traits, with genetic causality analyses supporting a substantial role for pleiotropy. Enrichment analysis, fine-mapping of urate-associated loci and colocalization with gene expression in 47 tissues implicated the kidney and liver as the main target organs and prioritized potentially causal genes and variants, including the transcriptional master regulators in the liver and kidney, HNF1A and HNF4A. Experimental validation showed that HNF4A transactivated the promoter of ABCG2, encoding a major urate transporter, in kidney cells, and that HNF4A p.Thr139Ile is a functional variant. Transcriptional coregulation within and across organs may be a general mechanism underlying the observed pleiotropy between urate and cardiometabolic traits.

4.
JAMA Neurol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566685

RESUMO

Importance: Determining whether the previously reported decreased stroke incidence rates from 1987 to 2011 among US adults 65 years and older in the Atherosclerosis Risk in Communities (ARIC) study continued to decrease subsequently can help guide policy and planning efforts. Objective: To evaluate whether stroke incidence declines among older adults in the ARIC study continued after 2011. Design, Setting, and Participants: ARIC is a community-based prospective cohort study including 15 792 individuals aged 45 to 64 years at baseline (1987-1989), selected by probability sampling from residents of Forsyth County, North Carolina; Jackson, Mississippi (black individuals only); the northwestern suburbs of Minneapolis, Minneapolis; and Washington County, Maryland (ie, center). The present study included ARIC participants free of stroke at baseline, followed up through December 31, 2017. Data were collected through personal interviews and physical examinations during study visits, annual/semiannual telephone interviews, and active surveillance of discharges from local hospitals. Stroke events were adjudicated by study-physicians reviewers. Analysis began September 2018. Main Outcomes and Measures: The main outcome was stroke incidence rates, which were computed with 95% CIs stratifying the analysis by age and calendar time. Trends in adjusted incidence rates were assessed using Poisson regression incidence rate ratios. Models included calendar time, age, sex, race/center, and time-varying risk factors (hypertension, diabetes, coronary heart disease, cholesterol-lowering medication use, and smoking). Results: Of 14 357 ARIC participants with 326 654 person-years of follow-up, the mean (SD) age at baseline was 54.1 (5.8) years and 7955 (55.4%) were women. From 1987 to 2017, a total of 1340 incident strokes occurred among ARIC participants, and among them, 1028 (76.7%) occurred in participants 65 years and older. Crude incidence rates of stroke for participants 65 years and older decreased progressively from 1987 to 2017. Incidence rates, adjusted for age, sex, race/center, and time-varying risk factors, decreased by 32% (95% CI, 23%-40%) per 10 years in participants 65 years and older. Findings were consistent across decades, sex, and race. Conclusions and Relevance: Validated total stroke incidence rates in adults 65 years and older decreased over the last 30 years in the ARIC cohort. The decrease in rates previously reported for 1987 to 2011 extends for the subsequent 6 years in men and women as well as in white and black individuals.

5.
Circ Arrhythm Electrophysiol ; 12(10): e007390, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31607148

RESUMO

BACKGROUND: The prevalence of subclinical atrial fibrillation (AF) in the elderly general population is unclear. We sought to define the prevalence of subclinical AF in a community-based elderly population and to characterize subclinical AF and the incremental diagnostic yield of 4 versus 2 weeks of continuous ECG monitoring. METHODS: We conducted a cross-sectional analysis within the community-based multicenter observational ARIC study (Atherosclerosis Risk in Communities) using visit 6 (2016-2017) data. The 2616 ARIC study participants who wore a leadless, ambulatory ECG monitor (Zio XT Patch) for up to 2 weeks were aged 79±5 years, 42% men, and 26% black. In a subset, 386 participants without clinically recognized AF wore the monitor twice, each time for up to 2 weeks. We characterized the prevalence of subclinical AF (ie, AF detected on the Zio XT Patch without clinically recognized AF) over 2 weeks of monitoring and the diagnostic yield of 4 versus 2 weeks of monitoring. RESULTS: The prevalence of subclinical AF was 2.5%; the prevalence of subclinical AF was 3.3% among white men, 2.5% among white women, 2.1% among black men, and 1.6% among black women. Subclinical AF was mostly intermittent (75%). Among those with intermittent subclinical AF, 91% had AF burden ≤10% during the monitoring period. In a subset of 386 participants without clinical AF, 78% more subclinical AF was detected by 4 weeks versus 2 weeks of ECG monitoring. CONCLUSIONS: In our study, the prevalence of subclinical AF was lower than previously reported and monitoring beyond 2 weeks provided substantial incremental diagnostic yield. Future studies should focus on individuals with higher risk to increase diagnostic yield and consider continuous monitoring duration longer than 2 weeks.

6.
Mayo Clin Proc ; 2019 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-31619367

RESUMO

OBJECTIVE: To assess the patterns of angiotensin converting enzyme inhibitors and angiotensin receptor blockers (ACE-I/ARB) discontinuation in the setting of chronic kidney disease (CKD) progression in real-world clinical practice. PATIENTS AND METHODS: We identified incident ACE-I/ARB users with a baseline estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2 and without end-stage renal disease in the Geisinger Health System between January 1, 2004, and December 31, 2015. We investigated the associations of CKD stage, hospitalizations with and without acute kidney injury (AKI), serum potassium, bicarbonate level, thiazide, and loop diuretic use with ACE-I/ARB discontinuation. RESULTS: Among the 53,912 ACE-I/ARB users, the mean age was 59.9 years, and 50.6% were female. More than half of users discontinued ACE-I/ARB within 5 years of therapy initiation. The risk of ACE-I/ARB discontinuation increased with more advanced CKD stage. For example, patients who initiated ACE-I/ARB with CKD stage G4 (eGFR: 15-29 mL/min/1.73 m2) were 2.09-fold (95% CI, 1.87-2.34) more likely to discontinue therapy than those with eGFR ≥ 90 mL/min/1.73 m2. Potassium level greater than 5.3 mEq/L, systolic blood pressure ≤ 90 mm Hg, bicarbonate level < 22 mmol/L, and intervening hospitalization-particularly AKI-related-were also strong risk factors for ACE-I/ARB discontinuation. Thiazide diuretic use was associated with lower risk, whereas loop diuretic use was associated with higher risk of discontinuation. CONCLUSION: In a real-world cohort, discontinuation of ACE-I/ARB was common, particularly in patients with lower eGFR. Hyperkalemia, hypotension, low bicarbonate level, and hospitalization (AKI-related, in particular) were associated with a higher risk of ACE-I/ARB discontinuation. Additional studies are needed to evaluate the risk-benefit balance of discontinuing ACE-I/ARB in the setting of CKD progression.

7.
J Appl Lab Med ; 4(1): 30-39, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31639705

RESUMO

BACKGROUND: There is growing interest in the use of multiplexed aptamer-based assays for large-scale proteomic studies. However, the analytic, short- and long-term variation of the measured proteins is largely uncharacterized. METHODS: We quantified 4001 plasma protein analytes from 42 participants in the Atherosclerosis Risk in Communities (ARIC) Study in split samples and at multiple visits using a multiplexed modified aptamer assay. We calculated the CV, Spearman correlation, and intraclass correlation (ICC) between split samples and evaluated the short-term (4-9 weeks) and long-term (approximately 20 years) variability using paired t-tests with log-transformed protein concentrations and Bonferroni-corrected significance thresholds. We performed principal component (PC) analysis of protein analyte concentrations and evaluated their associations with age, sex, race, and estimated glomerular filtration rate (eGFR). RESULTS: The mean baseline age was 57 years at the first visit, 43% of participants were male and 57% were white. Among 3693 protein analytes that passed quality control, half (n = 1846) had CVs < 5.0%, Spearman correlations > 0.89, and ICCs > 0.96 among the split samples. Over the short term, only 1 analyte had a statistically significant difference between the 2 time points, whereas, over approximately 20 years, 866 analytes (23.4%) had statistically significant differences (P < 1.4 × 10-5, 681 increased, 185 decreased). PC1 had high correlations with age (-0.73) and eGFR (0.60). PC2 had moderate correlation with male sex (0.18) and white race (0.31). CONCLUSIONS: Multiplexed modified aptamer technology can assay thousands of proteins with excellent precision. Our results support the potential for large-scale studies of the plasma proteome over the lifespan.

8.
Nat Commun ; 10(1): 4130, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31511532

RESUMO

Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria.

9.
Nat Rev Nephrol ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31527790

RESUMO

Evaluation of glomerular filtration rate (GFR) is central to the assessment of kidney function in medical practice, research and public health. Measured GFR (mGFR) remains the reference standard, but the past 20 years have seen major advances in estimated GFR (eGFR). Both eGFR and mGFR are associated with error compared with true GFR. eGFR is now recommended by clinical practice guidelines, regulatory agencies and public health agencies for the initial evaluation of GFR, with measured GFR (mGFR) typically considered an important confirmatory test, depending on how accurate the assessment of GFR needs to be for application to the clinical, research or public health setting. Our approach is to use initial and confirmatory tests as needed to develop a final assessment of true GFR. We suggest that GFR evaluation might be improved by more complete implementation of current recommendations and by further research to improve the accuracy of mGFR and eGFR.

10.
J Nutr ; 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529069

RESUMO

BACKGROUND: The Healthy Eating Index-2015 (HEI-2015) score measures adherence to recommendations from the 2015-2020 Dietary Guidelines for Americans. The HEI-2015 was altered from the HEI-2010 by reclassifying sources of dietary protein and replacing the empty calories component with 2 new components: saturated fats and added sugars. OBJECTIVES: Our aim was to assess whether the HEI-2015 score, along with 3 other previously defined indices, were associated with incident cardiovascular disease (CVD), CVD mortality, and all-cause mortality. METHODS: We conducted a prospective analysis of 12,413 participants aged 45-64 y (56% women) from the Atherosclerosis Risk in Communities (ARIC) Study. The HEI-2015, Alternative Healthy Eating Index-2010 (AHEI-2010), alternate Mediterranean (aMed) diet, and Dietary Approaches to Stop Hypertension Trial (DASH) scores were computed using the average dietary intakes of Visits 1 (1987-1989) and 3 (1993-1995). Incident CVD, CVD mortality, and all-cause mortality data were ascertained from baseline through 31 December, 2017. We used Cox proportional hazards models to estimate HRs and 95% CIs. RESULTS: There were 4509 cases of incident CVD, 1722 cases of CVD mortality, and 5747 cases of all-cause mortality over a median of 24-25 y of follow-up. Compared with participants in the lowest quintile of HEI-2015, participants in the highest quintile had a 16% lower risk of incident CVD (HR: 0.84; 95% CI: 0.76-0.93; P-trend < 0.001), 32% lower risk of CVD mortality (HR: 0.68; 95% CI: 0.58-0.80; P-trend < 0.001), and 18% lower risk of all-cause mortality (HR: 0.82; 95% CI: 0.75-0.89; P-trend < 0.001) after adjusting for demographic and lifestyle covariates. There were similar protective associations for AHEI-2010, aMed, and DASH scores, and no significant interactions by race. CONCLUSIONS: Higher adherence to the 2015-2020 Dietary Guidelines for Americans was associated with lower risks of incident CVD, CVD mortality, and all-cause mortality among US adults.

11.
J Am Heart Assoc ; 8(18): e012177, 2019 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-31500474

RESUMO

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.

12.
Am J Kidney Dis ; 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31492486

RESUMO

Diabetes is the leading cause of kidney failure worldwide, whereas glomerulonephritis has been predominant in developing countries such as China. The prevalence of obesity and diabetes has increased dramatically in developing countries, substantially affecting the patterns of chronic kidney disease (CKD) observed in these regions. Using data from the Hospital Quality Monitoring System to evaluate changes in the spectrum of non-dialysis-dependent CKD in China, we have observed an increase in the percentage of patients with CKD due to diabetes, which has exceeded that of CKD due to glomerulonephritis since 2011, as well as an increase in hypertensive nephropathy and, in some regions, obstructive kidney disease (mostly associated with kidney stones). The growth of noncommunicable diseases under profound societal and environmental changes has shifted the spectrum of CKD in China toward patterns similar to those of developed countries, which will have enormous impacts on the Chinese health care system. There is much to be done regarding public health interventions, including the establishment of a national CKD surveillance system, improvement in the management of diabetes and hypertension, and enhancement of the affordability and accessibility of kidney replacement therapy. Reducing the burden of CKD will require joint efforts from government, the medical community (including practitioners other than nephrologists), and the public.

13.
Am J Kidney Dis ; 2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31473020

RESUMO

The US Food and Drug Administration (FDA) and European Medicines Agency (EMA) are currently willing to consider a 30% to 40% glomerular filtration rate (GFR) decline as a surrogate end point for kidney failure for clinical trials of kidney disease progression under appropriate conditions. However, these end points may not be practical for early stages of kidney disease. In March 2018, the National Kidney Foundation sponsored a scientific workshop in collaboration with the FDA and EMA to evaluate changes in albuminuria or GFR as candidate surrogate end points. Three parallel efforts were presented: meta-analyses of observational studies (cohorts), meta-analyses of clinical trials, and simulations of trial design. In cohorts, after accounting for measurement error, relationships between change in urinary albumin-creatinine ratio (UACR) or estimated GFR (eGFR) slope and the clinical outcome of kidney disease progression were strong and consistent. In trials, the posterior median R2 of treatment effects on the candidate surrogates with the clinical outcome was 0.47 (95% Bayesian credible interval [BCI], 0.02-0.96) for early change in UACR and 0.72 (95% BCI, 0.05-0.99) when restricted to baseline UACR>30mg/g, and 0.97 (95% BCI, 0.78-1.00) for total eGFR slope at 3 years and 0.96 (95% BCI, 0.63-1.00) for chronic eGFR slope (ie, the slope excluding the first 3 months from baseline, when there might be acute changes in eGFR). The magnitude of the relationships of changes in the candidate surrogates with risk for clinical outcome was consistent across cohorts and trials: a UACR reduction of 30% or eGFR slope reduction by 0.5 to 1.0mL/min/1.73m2 per year were associated with an HR of ∼0.7 for the clinical outcome in cohorts and trials. In simulations, using GFR slope as an end point substantially reduced the required sample size and duration of follow-up compared with the clinical end point when baseline eGFR was high, treatment effects were uniform, and there was no acute effect of the treatment. We conclude that both early change in albuminuria and GFR slope fulfill criteria for surrogacy for use as end points in clinical trials for chronic kidney disease progression under certain conditions, with stronger support for change in GFR than albuminuria. Implementation requires understanding conditions under which each surrogate is likely to perform well and restricting its use to those settings.

14.
Am J Clin Nutr ; 110(3): 713-721, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31386145

RESUMO

BACKGROUND: Adherence to healthy dietary patterns, measured by the Healthy Eating Index (HEI), Alternative Healthy Eating Index (AHEI), and alternate Mediterranean diet (aMed) scores, is associated with a reduced risk of cardiovascular disease. The association between these scores and chronic kidney disease (CKD) is undetermined. OBJECTIVE: We aimed to estimate the association between the HEI, AHEI, and aMed scores and risk of incident CKD. METHODS: We conducted a prospective analysis in 12,155 participants aged 45-64 y from the Atherosclerosis Risk in Communities (ARIC) Study. We calculated HEI-2015, AHEI-2010, and aMed scores for each participant and categorized them into quintiles of each dietary score. Incident CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 accompanied by ≥25% decline in estimated glomerular filtration rate, a kidney disease-related hospitalization or death, or end-stage renal disease. We used cause-specific hazard models to estimate risk of CKD from the quintile of the dietary score through to 31 December 2017. RESULTS: There were 3980 cases of incident CKD over a median follow-up of 24 y. Participants who had higher adherence to the HEI-2015, AHEI-2010, and aMed scores were more likely to be female, have higher educational attainment, higher income level, be nonsmokers, more physically active, and diabetic compared with participants who scored lower. All 3 dietary scores were associated with lower CKD risk (P-trend < 0.001). Participants who were in the highest quintile of HEI-2015 score had a 17% lower risk of CKD (HR: 0.83; 95% CI: 0.74, 0.92) compared with participants in the lowest quintile. Those in quintile 5 of AHEI-2010 and aMed scores, respectively, had a 20% and 13% lower risk of CKD compared with those in quintile 1. CONCLUSION: Higher adherence to healthy dietary patterns during middle age was associated with lower risk of CKD.

15.
PLoS One ; 14(8): e0219899, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31393910

RESUMO

BACKGROUND: Although hypokalemia has been viewed as a significant concern among patients with heart failure (HF), recent advances in HF management tend to increase the risk of hyperkalemia. OBJECTIVE: To characterize contemporary data regarding correlates and prognostic values of dyskalemia in patients with HF. DESIGN, SETTING, AND PARTICIPANTS: In cross-sectional and longitudinal analyses, we studied 142,087 patients with newly diagnosed HF in US nationwide Veterans Administration database from 2005 through 2013. EXPOSURES: Demographic characteristics, laboratory variables, comorbidities, and medication use for the analysis of correlates of dyskalemia as well as potassium level in the analysis of mortality. MAIN OUTCOMES AND MEASURES: Dyskalemia and mortality. RESULTS: Hypokalemia (<3.5 mmol/L) at baseline was observed in 3.0% of the population, whereas hyperkalemia (≥5.5 mmol/L) was seen in 0.9%. An additional 20.4% and 5.7% had mild hypokalemia (3.5-3.9 mmol/L) and mild hyperkalemia (5.0-5.4 mmol/L). Key correlates were black race, higher blood pressure, and use of potassium-wasting diuretics for hypokalemia, and lower kidney function for hyperkalemia. Baseline potassium levels showed a U-shaped association with mortality, with the lowest risk between 4.0-4.5 mmol/L. With respect to potassium levels over a year after HF diagnosis, persistent (>50% of measurements), intermittent (>1 occurrence but ≤50%), and transient (1 occurrence) hypo- and hyperkalemia were also related to increased mortality in a graded fashion regardless of the aforementioned thresholds for dyskalemia. These dyskalemic patterns were also related to other clinical actions and demands such as emergency room visit. CONCLUSIONS: Potassium levels below 4 mmol/L and above 5 mmol/L at and after HF diagnosis were associated with poor prognosis and the clinical actions. HF patients (particularly with risk factors for dyskalemia like black race and kidney dysfunction) may require special attention for both hypo- and hyperkalemia.

16.
JAMA ; 322(6): 535-545, 2019 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-31408138

RESUMO

Importance: The association between late-life blood pressure (BP) and cognition may depend on the presence and chronicity of past hypertension. Late-life declines in blood pressure following prolonged hypertension may be associated with poor cognitive outcomes. Objective: To examine the association of midlife to late-life BP patterns with subsequent dementia, mild cognitive impairment, and cognitive decline. Design, Setting, and Participants: The Atherosclerosis Risk in Communities prospective population-based cohort study enrolled 4761 participants during midlife (visit 1, 1987-1989) and followed-up over 6 visits through 2016-2017 (visit 6). BP was examined over 24 years at 5 in-person visits between visits 1 and 5 (2011-2013). During visits 5 and 6, participants underwent detailed neurocognitive evaluation. The setting was 4 US communities: Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis, Minnesota. Follow-up ended on December 31, 2017. Exposures: Five groups based on longitudinal patterns of normotension, hypertension (>140/90 mm Hg), and hypotension (<90/60 mm Hg) at visits 1 to 5. Main Outcomes and Measures: Primary outcome was dementia onset after visit 5, based on Ascertain Dementia-8 informant questionnaires, Six-Item Screener telephone assessments, hospital discharge and death certificate codes, and the visit 6 neurocognitive evaluation. Secondary outcome was mild cognitive impairment at visit 6, based on the neurocognitive evaluation. Results: Among 4761 participants (2821 [59%] women; 979 [21%] black race; visit 5 mean [SD] age, 75 [5] years; visit 1 mean age range, 44-66 years; visit 5 mean age range, 66-90 years), there were 516 (11%) incident dementia cases between visits 5 and 6. The dementia incidence rate for participants with normotension in midlife (n = 833) and late life was 1.31 (95% CI, 1.00-1.72 per 100 person-years); for midlife normotension and late-life hypertension (n = 1559), 1.99 (95% CI, 1.69-2.32 per 100 person-years); for midlife and late-life hypertension (n = 1030), 2.83 (95% CI, 2.40-3.35 per 100 person-years); for midlife normotension and late-life hypotension (n = 927), 2.07 (95% CI, 1.68-2.54 per 100 person-years); and for midlife hypertension and late-life hypotension (n = 389), 4.26 (95% CI, 3.40-5.32 per 100 person-years). Participants in the midlife and late-life hypertension group (hazard ratio [HR], 1.49 [95% CI, 1.06-2.08]) and in the midlife hypertension and late-life hypotension group (HR, 1.62 [95% CI, 1.11-2.37]) had significantly increased risk of subsequent dementia compared with those who remained normotensive. Irrespective of late-life BP, sustained hypertension in midlife was associated with dementia risk (HR, 1.41 [95% CI, 1.17-1.71]). Compared with those who were normotensive in midlife and late life, only participants with midlife hypertension and late-life hypotension had higher risk of mild cognitive impairment (37 affected individuals (odds ratio, 1.65 [95% CI, 1.01-2.69]). There was no significant association of BP patterns with late-life cognitive change. Conclusions and Relevance: In this community-based cohort with long-term follow-up, sustained hypertension in midlife to late life and a pattern of midlife hypertension and late-life hypotension, compared with midlife and late-life normal BP, were associated with increased risk for subsequent dementia.


Assuntos
Disfunção Cognitiva/complicações , Demência/etiologia , Hipertensão/complicações , Adulto , Idoso , Pressão Sanguínea , Determinação da Pressão Arterial , Disfunção Cognitiva/etiologia , Estudos de Coortes , Feminino , Humanos , Hipotensão/complicações , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
17.
Am Heart J ; 216: 62-73, 2019 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-31404723

RESUMO

High-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) at the time of myocardial infarction (MI) are strong predictors of prognosis. However, whether their premorbid (before MI occurrence) levels are associated with prognosis after incident MI is unknown. METHODS: In 1,054 participants from the Atherosclerosis Risk in Communities Study with incident MI, we evaluated premorbid levels of hs-cTnT and NT-proBNP measured on median 5.8 (interquartile interval 3.0-11.5 [mean 5.5]) years prior to incident MI and their associations with subsequent composite and individual outcomes of all-cause mortality, cardiovascular mortality, recurrent MI, heart failure, and stroke. RESULTS: During a median follow-up of 3.0 years after MI, 801 participants developed the composite outcome. Both hs-cTnT and NT-proBNP were independently associated with the composite outcome after incident MI. Among individual outcomes, all-cause mortality, cardiovascular mortality, and heart failure showed significant associations with both cardiac markers. Overall, NT-proBNP demonstrated a more evident relationship than hs-cTnT. Indeed, the addition of premorbid NT-proBNP alone, but not hs-cTnT alone, to conventional predictors at incident MI significantly improved risk prediction of the composite outcome after incident MI (∆c-statistic 0.013 [95% CI 0.005-0.022] from 0.691 with conventional predictors). CONCLUSIONS: Premorbid levels of hs-cTnT and NT-proBNP assessed on average 6 years prior to incident MI were associated with adverse outcomes after incident MI. These results further highlight the importance of cardiac health at an earlier stage of life.

18.
J Am Soc Nephrol ; 30(10): 2027-2036, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31383730

RESUMO

BACKGROUND: Two coding variants in the apo L1 gene (APOL1) are strongly associated with kidney disease in blacks. Kidney disease itself increases the risk of cardiovascular disease, but whether these variants have an independent direct effect on the risk of cardiovascular disease is unclear. Previous studies have had inconsistent results. METHODS: We conducted a two-stage individual participant data meta-analysis to assess the association of APOL1 kidney-risk variants with adjudicated cardiovascular disease events and death, independent of kidney measures. The analysis included 21,305 blacks from eight large cohorts. RESULTS: Over 8.9±5.0 years of follow-up, 2076 incident cardiovascular disease events occurred in the 16,216 participants who did not have cardiovascular disease at study enrollment. In fully-adjusted analyses, individuals possessing two APOL1 kidney-risk variants had similar risk of incident cardiovascular disease (coronary heart disease, myocardial infarction, stroke and heart failure; hazard ratio 1.11, 95% confidence interval, 0.96 to 1.28) compared to individuals with zero or one kidney-risk variant. The risk of coronary heart disease, myocardial infarction, stroke and heart failure considered individually was also comparable by APOL1 genotype. APOL1 genotype was also not associated with death. There was no difference in adjusted associations by level of kidney function, age, diabetes status, or body-mass index. CONCLUSIONS: In this large, two-stage individual participant data meta-analysis, APOL1 kidney-risk variants were not associated with incident cardiovascular disease or death independent of kidney measures.

19.
Eur J Prev Cardiol ; : 2047487319865378, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362534

RESUMO

AIMS: The aim of this study was to evaluate the associations of blood pressure categorization based on the 2017 American College of Cardiology and American Heart Association guideline with the risk of peripheral artery disease (PAD). METHODS: Among 13,113 middle-aged participants, we investigated the associations of 2017 blood pressure categories (systolic <120 and diastolic <80 mmHg (normal if no anti-hypertensive medications; reference), 120-129 and <80 (elevated), 130-139 and/or 80-89 (stage 1 hypertension), and ≥140 and/or ≥90 (stage 2 hypertension)) with incident PAD (hospitalizations with a diagnosis or leg revascularization) using Cox regression models. Analyses were separately conducted in individuals with and without anti-hypertensive medications. RESULTS: During a median follow-up of 25.4 years, 466 incident PAD occurred (271 cases in 9858 participants without anti-hypertensive medications). In participants without anti-hypertensive medications, we observed significant hazard ratios of PAD in elevated blood pressure (1.80 (1.28-2.51)) and stage 2 hypertension (2.40 (1.72-3.34)), but not in stage 1 hypertension. Analyzing systolic and diastolic blood pressure separately, higher systolic blood pressure categories showed significant associations with incident PAD in a graded fashion whereas, for diastolic blood pressure, only ≥90 mmHg did. Generally similar patterns were seen among participants on anti-hypertensive medication, while they had higher risk of PAD than those without at each blood pressure category. CONCLUSIONS: Systolic blood pressure, including the category of 130-139 mmHg, showed stronger associations with incident PAD than did diastolic blood pressure. Consequently, elevated blood pressure conferred similar or even greater risk of PAD than stage 1 hypertension, with implications on how to interpret new blood pressure categories in terms of leg vascular health.

20.
J Am Heart Assoc ; 8(16): e012865, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31387433

RESUMO

Background Previous studies have documented the cardiometabolic health benefits of plant-based diets; however, these studies were conducted in selected study populations that had narrow generalizability. Methods and Results We used data from a community-based cohort of middle-aged adults (n=12 168) in the ARIC (Atherosclerosis Risk in Communities) study who were followed up from 1987 through 2016. Participants' diet was classified using 4 diet indexes. In the overall plant-based diet index and provegetarian diet index, higher intakes of all or selected plant foods received higher scores; in the healthy plant-based diet index, higher intakes of only the healthy plant foods received higher scores; in the less healthy plant-based diet index, higher intakes of only the less healthy plant foods received higher scores. In all indexes, higher intakes of animal foods received lower scores. Results from Cox proportional hazards models showed that participants in the highest versus lowest quintile for adherence to overall plant-based diet index or provegetarian diet had a 16%, 31% to 32%, and 18% to 25% lower risk of cardiovascular disease, cardiovascular disease mortality, and all-cause mortality, respectively, after adjusting for important confounders (all P<0.05 for trend). Higher adherence to a healthy plant-based diet index was associated with a 19% and 11% lower risk of cardiovascular disease mortality and all-cause mortality, respectively, but not incident cardiovascular disease (P<0.05 for trend). No associations were observed between the less healthy plant-based diet index and the outcomes. Conclusions Diets higher in plant foods and lower in animal foods were associated with a lower risk of cardiovascular morbidity and mortality in a general population.

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