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1.
Kidney Int ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33961868

RESUMO

Chronic kidney disease (CKD) affects about 10% of all populations worldwide, with about 2 million people requiring dialysis. Although patients with CKD are at high risk of cardiovascular disease (CVD) and events, they are often underrepresented or excluded in clinical trials, leading to important knowledge gaps about how to treat these patients. KDIGO (Kidney Disease: Improving Global Outcomes) convened the fourth Clinical Controversies Conference on the Heart, Kidney and Vasculature in Dublin, Ireland, in February 2020, entitled "Central and Peripheral Arterial Diseases in Chronic Kidney Disease." A global panel of multidisciplinary experts from the fields of nephrology, cardiology, neurology, surgery, radiology, vascular biology, epidemiology and health economics attended. The objective was to identify key issues related to the optimal detection, management, and treatment of cerebrovascular diseases, central aortic disease, renovascular disease, and peripheral arterial disease in the setting of CKD. This report will outline the common pathophysiology of these vascular processes in the setting of CKD, describe best practices for their diagnosis and management, summarize areas of uncertainty, address ongoing controversial issues, and propose a research agenda to address key gaps in knowledge that, when addressed, could improve patient care and outcomes.

2.
Medicine (Baltimore) ; 100(18): e25845, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33950999

RESUMO

ABSTRACT: We examined the association between diuretic administration before the diagnosis of minimal change disease and the incidence of acute kidney injury. Moreover, we examined whether the use of diuretics affected the time to complete remission in adults with such disease.The present study was a single-center, retrospective, observational cohort study. We included 107 patients with biopsy-proven minimal change disease who were treated at a tertiary referral center in Japan between January 1, 2000 and March 31, 2019. All biopsy specimens were examined by a board-certified renal pathologist. The patients were considered to have minimal change disease when the kidney biopsy specimen had no glomerular lesions or only mild focal mesangial prominence (not exceeding 3 or 4 cells per segment) by light microscopy and/or foot process effacement by electron microscopy. Logistic regression and Kaplan-Meier curve analyses were performed, comparing the data of patients who received diuretics or not.The median age was 47 (28-66) years, 52% of patients were women, and the median proteinuria dosage was 8.3 (5.3-11.2) g/d. When minimal change disease was diagnosed, 27% of patients were taking diuretics. Within 30 days after the diagnosis, acute kidney injury occurred in 27% of patients. On multivariable logistic regression analysis, the use of diuretics was significantly associated with a higher risk of acute kidney injury. The use of diuretics was also associated with a longer time to complete remission.Diuretic administration can be associated with an elevated acute kidney injury risk and longer remission time in adult patients with newly diagnosed minimal change disease.

3.
Eur J Heart Fail ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33928732

RESUMO

AIMS: African-American carriers of the transthyretin (TTR) valine-to-isoleucine substitution (V122I) are at increased risk of heart failure, yet many have relatively subtle abnormalities of left ventricular (LV) function. We sought to explore the influence of this mutation on left atrial (LA) structure and function in this population. METHODS AND RESULTS: We assessed 1,225 genotyped African-Americans (age range, 67-89 years) participating in the Atherosclerosis Risk in Communities Study who underwent echocardiography and were in sinus rhythm at study Visit 5 (2011 to 2013). Six LA parameters (LA maximum/minimum volume index, ejection fraction, and LA reservoir, conduit, and contractile longitudinal strains [LS]) were compared between V122I TTR variant carriers (n=46) and noncarriers (n=1,179). LA minimum volume index was significantly greater and LA contractile LS was worse in carriers than noncarriers (19.5 ± 10.6 ml/m2 vs 16.3 ± 8.4 ml/m2 ; 15.0 ± 5.8 % vs 16.8 ± 5.7 %, respectively, both P<0.05). Carriers had a significantly higher number of LA abnormalities than noncarriers (1.8 ± 2.2 vs 1.1 ± 1.6, P=0.009). The number of subjects with at least 4 LA abnormalities was significantly increased among carriers compared with noncarriers (27% vs 12%; odds ratio, 2.43; 95 % confidence interval, 1.06-5.58 after adjusted for age, sex, body mass index, and LV wall thickness and global LS). CONCLUSIONS: LA enlargement and dysfunction were more common in V122I TTR carriers with sinus rhythm, suggesting our findings generate hypotheses that LA assessment may provide the possibility of ATTR-CM along with LV assessment among elderly African-Americans.

5.
Arterioscler Thromb Vasc Biol ; : ATVBAHA120315692, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33882687

RESUMO

OBJECTIVE: Nonatherosclerotic outward remodeling of the large intracranial arteries may facilitate propagation of excessive aortic pulsatile energy into the cerebral microcirculation and has been associated with adverse cognitive outcomes. We sought to determine the relationship between central artery stiffness, brain arterial diameters, and white matter hyperintensity (WMH) volume in the general population of older adults. Approach and Results: We examined data from 1275 stroke-free participants of the ARIC (Atherosclerosis Risk in Communities) study (59% female, 30% Black, mean age 77 years) who underwent carotid-femoral pulse wave velocity (cf-PWV) testing and brain magnetic resonance imaging. A cf-PWV >12 m/s was considered elevated. Relationships between WMH and arterial diameters at the M1A1 segment of the middle and anterior cerebral arteries (whichever larger) were analyzed in the absence of artery-specific plaque, adjusting for intracranial volume and potential confounders. The average cf-PWV was 11.7 m/s and WMH volume was 11.2 cm3. Each 0.5 mm increment in M1A1 diameter was associated with 24% greater WMH volume in participants with elevated cf-PWV (exponentiated ß=1.24 [95% CI, 1.12-1.36]), compared with a 10% greater WMH volume in participants without elevated cf-PWV (exponentiated ß=1.10 [95% CI, 1.01-1.19]), P value for interaction=0.04. CONCLUSIONS: In this examination of older adults from the general population, larger, plaque-free arterial diameters in the middle cerebral circulation were associated with greater WMH volume, particularly among participants with elevated central artery stiffness. Strategies to reduce central artery stiffness may mitigate the association between cerebrovascular outward remodeling and microvascular damage.

6.
N Engl J Med ; 384(17): 1601-1612, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33913638

RESUMO

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor prolyl hydroxylase inhibitor, a class of compounds that stimulate endogenous erythropoietin production. METHODS: We conducted two randomized, open-label, noninferiority phase 3 trials to evaluate the safety and efficacy of vadadustat, as compared with darbepoetin alfa, in patients with anemia and incident or prevalent dialysis-dependent chronic kidney disease (DD-CKD). The primary safety end point, assessed in a time-to-event analysis, was the first occurrence of a major adverse cardiovascular event (MACE, a composite of death from any cause, a nonfatal myocardial infarction, or a nonfatal stroke), pooled across the trials (noninferiority margin, 1.25). A key secondary safety end point was the first occurrence of a MACE plus hospitalization for either heart failure or a thromboembolic event. The primary and key secondary efficacy end points were the mean change in hemoglobin from baseline to weeks 24 to 36 and from baseline to weeks 40 to 52, respectively, in each trial (noninferiority margin, -0.75 g per deciliter). RESULTS: A total of 3923 patients were randomly assigned in a 1:1 ratio to receive vadadustat or darbepoetin alfa: 369 in the incident DD-CKD trial and 3554 in the prevalent DD-CKD trial. In the pooled analysis, a first MACE occurred in 355 patients (18.2%) in the vadadustat group and in 377 patients (19.3%) in the darbepoetin alfa group (hazard ratio, 0.96; 95% confidence interval [CI], 0.83 to 1.11). The mean differences between the groups in the change in hemoglobin concentration were -0.31 g per deciliter (95% CI, -0.53 to -0.10) at weeks 24 to 36 and -0.07 g per deciliter (95% CI, -0.34 to 0.19) at weeks 40 to 52 in the incident DD-CKD trial and -0.17 g per deciliter (95% CI, -0.23 to -0.10) and -0.18 g per deciliter (95% CI, -0.25 to -0.12), respectively, in the prevalent DD-CKD trial. The incidence of serious adverse events in the vadadustat group was 49.7% in the incident DD-CKD trial and 55.0% in the prevalent DD-CKD trial, and the incidences in the darbepoetin alfa group were 56.5% and 58.3%, respectively. CONCLUSIONS: Among patients with anemia and CKD who were undergoing dialysis, vadadustat was noninferior to darbepoetin alfa with respect to cardiovascular safety and correction and maintenance of hemoglobin concentrations. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; INNO2VATE ClinicalTrials.gov numbers, NCT02865850 and NCT02892149.).


Assuntos
Anemia/tratamento farmacológico , Darbepoetina alfa/uso terapêutico , Glicina/análogos & derivados , Hematínicos/uso terapêutico , Ácidos Picolínicos/uso terapêutico , Inibidores de Prolil-Hidrolase/uso terapêutico , Diálise Renal/efeitos adversos , Insuficiência Renal Crônica/complicações , Idoso , Anemia/sangue , Anemia/etiologia , Doenças Cardiovasculares/induzido quimicamente , Darbepoetina alfa/efeitos adversos , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Hematínicos/efeitos adversos , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Picolínicos/efeitos adversos , Inibidores de Prolil-Hidrolase/efeitos adversos , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/terapia
7.
N Engl J Med ; 384(17): 1589-1600, 2021 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-33913637

RESUMO

BACKGROUND: Vadadustat is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor, a class of drugs that stabilize HIF and stimulate erythropoietin and red-cell production. METHODS: In two phase 3, randomized, open-label, active-controlled, noninferiority trials, we compared vadadustat with the erythropoiesis-stimulating agent (ESA) darbepoetin alfa in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD) not previously treated with an ESA who had a hemoglobin concentration of less than 10 g per deciliter and in patients with ESA-treated NDD-CKD and a hemoglobin concentration of 8 to 11 g per deciliter (in the United States) or 9 to 12 g per deciliter (in other countries). The primary safety end point, assessed in a time-to-event analysis, was the first major adverse cardiovascular event (MACE; a composite of death from any cause, nonfatal myocardial infarction, or nonfatal stroke), pooled across the two trials. Secondary safety end points included expanded MACE (MACE plus hospitalization for either heart failure or a thromboembolic event). The primary and key secondary efficacy end points in each trial were the mean change in hemoglobin concentration from baseline during two evaluation periods: weeks 24 through 36 and weeks 40 through 52. RESULTS: A total of 1751 patients with ESA-untreated NDD-CKD and 1725 with ESA-treated NDD-CKD underwent randomization in the two trials. In the pooled analysis, in which 1739 patients received vadadustat and 1732 received darbepoetin alfa, the hazard ratio for MACE was 1.17 (95% confidence interval [CI], 1.01 to 1.36), which did not meet the prespecified noninferiority margin of 1.25. The mean between-group differences in the change in the hemoglobin concentration at weeks 24 through 36 were 0.05 g per deciliter (95% CI, -0.04 to 0.15) in the trial involving ESA-untreated patients and -0.01 g per deciliter (95% CI, -0.09 to 0.07) in the trial involving ESA-treated patients, which met the prespecified noninferiority margin of -0.75 g per deciliter. CONCLUSIONS: Vadadustat, as compared with darbepoetin alfa, met the prespecified noninferiority criterion for hematologic efficacy but not the prespecified noninferiority criterion for cardiovascular safety in patients with NDD-CKD. (Funded by Akebia Therapeutics and Otsuka Pharmaceutical; PRO2TECT ClinicalTrials.gov numbers, NCT02648347 and NCT02680574.).


Assuntos
Anemia/tratamento farmacológico , Darbepoetina alfa/uso terapêutico , Glicina/análogos & derivados , Hematínicos/uso terapêutico , Ácidos Picolínicos/uso terapêutico , Inibidores de Prolil-Hidrolase/uso terapêutico , Insuficiência Renal Crônica/complicações , Administração Oral , Idoso , Anemia/sangue , Anemia/etiologia , Doenças Cardiovasculares/induzido quimicamente , Darbepoetina alfa/efeitos adversos , Feminino , Glicina/efeitos adversos , Glicina/uso terapêutico , Hematínicos/efeitos adversos , Hemoglobinas/análise , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Ácidos Picolínicos/efeitos adversos , Inibidores de Prolil-Hidrolase/efeitos adversos , Insuficiência Renal Crônica/mortalidade
8.
Atherosclerosis ; 324: 52-57, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33823370

RESUMO

BACKGROUND AND AIMS: Previous community-based studies have demonstrated sex and race-based disparities in the risk of cardiovascular disease. We sought to examine the association of sex and race with incident peripheral artery disease (PAD-) and critical limb ischemia (CLI-) related hospitalizations. METHODS: In 13,451 Black and White ARIC participants without prevalent PAD at baseline (1987-89), we estimated the cumulative incidence of PAD- and CLI-related hospitalization over a median follow-up of 26 years. We quantified hazard ratios (HRs) using Cox models across four sex- and race-groups. PAD and CLI were defined by hospitalization discharge codes. RESULTS: The cumulative incidence of PAD-related hospitalization was higher in males than females in Whites (5.1% vs. 2.7%; p<0.001) but not in Blacks (5.7% vs. 5.0%; p=0.39). The cumulative incidence of CLI-related hospitalization differed significantly by race more than sex, occurring in 3.1% Black males, 3.1% Black females, 1.4% White males, and 0.8% White females (p<0.001). After risk factor adjustment, the risk of incident PAD-related hospitalization was similar for White males vs. White females [HR 1.14, 95%CI 0.90-1.45], and slightly higher for Black males [HR 1.26, 95%CI 0.92-1.72] and Black females [HR 1.39, 95%CI 1.03-1.87] compared to White females. The adjusted risk of incident CLI-related hospitalization was similar for White males vs. White females [HR 1.15, 95%CI 0.75-1.76], and significantly higher for Black males [HR 1.96, 95%CI 1.22-3.16] and Black females [HR 2.06, 95%CI 1.31-3.24] compared to White females. CONCLUSIONS: These data suggest that there are both sex- and race-specific patterns of PAD-related hospitalization that lead to differences in clinical disease risk and presentation.

9.
J Am Heart Assoc ; 10(9): e016524, 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33880930

RESUMO

Background Black individuals have a higher burden of risk factors for heart failure (HF) and subclinical left ventricular remodeling. Methods and Results We evaluated 1871 Black participants in the Atherosclerosis Risk in Communities Study cohort who attended a routine examination (1993-1996, median age 58 years) when they underwent echocardiography. We estimated the prevalences of 4 HF stages: (1) Stage 0: no risk factors; (2) Stage A: presence of HF risk factors (hypertension, diabetes mellitus, obesity, smoking, dyslipidemia, coronary artery disease without clinical myocardial infarction), no cardiac structural/functional abnormality; (3) Stage B: presence of prior myocardial infarction, systolic dysfunction, left ventricular hypertrophy, regional wall motion abnormality, or left ventricular enlargement; and (4) Stage C/D: prevalent HF. We assessed the incidence of clinical HF, atherosclerotic cardiovascular disease events, and all-cause mortality on follow-up according to HF stage. The prevalence of HF Stages 0, A, B, and C/D were 3.8%, 20.6%, 67.0%, and 8.6%, respectively, at baseline. On follow-up (median 19.0 years), 309 participants developed overt HF, 390 incurred new-onset cardiovascular disease events, and 651 individuals died. Incidence rates per 1000 person-years for overt HF, cardiovascular disease events, and death, respectively, were Stage 0, 2.4, 0.8, and 7.6; Stage A, 7.4, 9.7, and 13.5; Stage B 13.6, 15.9, and 22.0. Stage B HF was associated with a 1.5- to 2-fold increased adjusted risk of HF, cardiovascular disease events and death compared with Stages 0/A. Conclusions In our large community-based sample of Black individuals, we observed a strikingly high prevalence of Stage B HF in middle age that was a marker of high cardiovascular morbidity and mortality.

10.
Circulation ; 143(17): e875-e891, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33761757

RESUMO

Nontraumatic lower-extremity amputation is a devastating complication of peripheral artery disease (PAD) with a high mortality and medical expenditure. There are ≈150 000 nontraumatic leg amputations every year in the United States, and most cases occur in patients with diabetes. Among patients with diabetes, after an ≈40% decline between 2000 and 2009, the amputation rate increased by 50% from 2009 to 2015. A number of evidence-based diagnostic and therapeutic approaches for PAD can reduce amputation risk. However, their implementation and adherence are suboptimal. Some racial/ethnic groups have an elevated risk of PAD but less access to high-quality vascular care, leading to increased rates of amputation. To stop, and indeed reverse, the increasing trends of amputation, actionable policies that will reduce the incidence of critical limb ischemia and enhance delivery of optimal care are needed. This statement describes the impact of amputation on patients and society, summarizes medical approaches to identify PAD and prevent its progression, and proposes policy solutions to prevent limb amputation. Among the actions recommended are improving public awareness of PAD and greater use of effective PAD management strategies (eg, smoking cessation, use of statins, and foot monitoring/care in patients with diabetes). To facilitate the implementation of these recommendations, we propose several regulatory/legislative and organizational/institutional policies such as adoption of quality measures for PAD care; affordable prevention, diagnosis, and management; regulation of tobacco products; clinical decision support for PAD care; professional education; and dedicated funding opportunities to support PAD research. If these recommendations and proposed policies are implemented, we should be able to achieve the goal of reducing the rate of nontraumatic lower-extremity amputations by 20% by 2030.

11.
JAMA Cardiol ; 6(5): 509-520, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33729428

RESUMO

Importance: Limited data exist regarding the association of subtle subclinical systolic dysfunction and incident heart failure (HF) in late life. Objective: To assess the independent associations of subclinical impairments in systolic performance with incident HF in late life. Design, Setting, and Participants: This study was a time-to-event analysis of participants without heart failure in the Atherosclerosis Risk in Communities (ARIC) study, a prospective, community-based cohort study, who underwent protocol echocardiography at the fifth study visit (January 1, 2011, to December 31, 2013). Findings were validated independently in participants in the Copenhagen City Heart Study (CCHS). Data analysis was performed from June 1, 2018, to February 28, 2020. Exposures: Left ventricular ejection fraction (LVEF), longitudinal strain (LS), and circumferential strain (CS) measured by 2-dimensional and strain echocardiography. Main Outcomes and Measures: Main outcomes were incident adjudicated HF and HF with preserved and reduced LVEF at a median follow-up of 5.5 years (interquartile range, 5.0-5.8 years). Cox proportional hazards regression models adjusted for demographics, hypertension, diabetes, obesity, smoking, coronary disease, estimated glomerular filtration rate, LV mass index, e', E/e', and left atrial volume index. Lower 10th percentile limits were determined in 374 participants free of cardiovascular disease or risk factors. Results: Among 4960 ARIC participants (mean [SD] age, 75 [5] years; 2933 [59.0%] female; 965 [19%] Black), LVEF was less than 50% in only 76 (1.5%). In the 3552 participants with complete assessment of LVEF, LS, and CS, 983 (27.7%) had 1 or more of the following findings: LVEF less than 60%, LS less than 16.0%, or CS less than 23.7%. Modeled continuously or dichotomized, worse LVEF, LS, and CS were each independently associated with incident HF. The adjusted hazard ratio (HR) per SD decrease in LVEF was 1.41 (95% CI, 1.29-1.55); the HR for LVEF less than 60% was 2.59 (95% CI, 1.99-3.37). Similar findings were observed for continuous LS (HR, 1.37; 95% CI, 1.22-1.53) and dichotomized LS (HR, 1.93; 95% CI, 1.46-2.55) and for continuous CS (HR, 1.39; 95% CI, 1.22-1.57) and dichotomized CS (HR, 2.30; 95% CI, 1.64-3.22). Although the magnitude of risk for incident HF or death associated with impaired LVEF was greater using guideline (HR, 2.99; 95% CI, 2.19-4.09) compared with ARIC-based limits (HR, 1.88; 95% CI, 1.58-2.25), the number of participants classified as impaired was less (104 [2.1%] based on guideline thresholds compared with 692 [13.9%] based on LVEF <60%). The population-attributable risk associated with LVEF less than 60% was 11% compared with 5% using guideline-based limits, a finding replicated in 908 participants in the CCHS. Conclusions and Relevance: These findings suggest that relatively subtle impairments of systolic function (detected based on LVEF or strain) are independently associated with incident HF and HF with reduced LVEF in late life. Current recommended assessments of LV function may substantially underestimate the prevalence of prognostically important impairments in systolic function in this population.

12.
Stroke ; : STROKEAHA120032695, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33784831

RESUMO

BACKGROUND AND PURPOSE: The association of physical activity (PA) before stroke (prestroke PA) with long-term prognosis after stroke is still unclear. We examined the association of prestroke PA with adverse health outcomes in the ARIC study (Atherosclerosis Risk in Communities). METHODS: We included 881 participants with incident stroke occurring between 1993 and 1995 (visit 3) and December 31, 2016. Follow-up continued until December 31, 2017 to allow for at least 1-year after incident stroke. Prestroke PA was assessed using a modified version of the Baecke questionnaire in 1987 to 1989 (visit 1) and 1993 to 1995 (visit 3), evaluating PA domains (work, leisure, and sports) and total PA. We used Cox proportional hazards models to quantify the association between tertiles of accumulated prestroke PA levels over the 6-year period between visits 1 and 3 and mortality, risk of cardiovascular disease, and recurrent stroke after incident stroke. RESULTS: During a median follow-up of 3.1 years after incident stroke, 676 (77%) participants had adverse outcomes. Highest prestroke total PA was associated with decreased risks of all-cause mortality (hazard ratio, 0.78 [95% CI, 0.63-0.97]) compared with lowest tertile. In the analysis by domain-specific PA, highest levels of work PA were associated with lower risk for all-cause (hazard ratio, 0.77 [95% CI, 0.62-0.96]) and cardiovascular mortality (hazard ratio, 0.45 [95% CI, 0.29-0.70]), and highest levels of leisure PA were associated with lower all-cause mortality (hazard ratio, 0.72 [95% CI, 0.58-0.89]) compared with lowest tertile of PA. No significant associations for sports PA were observed. CONCLUSIONS: Higher levels of total prestroke PA as well as work and leisure PA were associated with lower risk of mortality after incident stroke. Public health strategies to increase lifetime PA should be encouraged to decrease long-term mortality after stroke.

13.
J Hypertens ; 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33560059

RESUMO

BACKGROUND: The aortic to femoral arterial stiffness gradient (af-SG) may be a novel measure of arterial health and cardiovascular disease (CVD) risk, but its association with CVD risk factors and CVD status, and whether or not they differ from the referent measure, carotid-femoral pulse-wave velocity (cfPWV), is not known. METHOD: Accordingly, we compared the associations of the af-SG and cfPWV with (i) age and traditional CVD risk factors and (ii) CVD status. We evaluated 4183 older-aged (75.2 ±â€Š5.0 years) men and women in the community-based Atherosclerosis Risk in Communities (ARIC) Study. cfPWV and femoral-ankle PWV (faPWV) were measured using an automated cardiovascular screening device. The af-SG was calculated as faPWV divided by cfPWV. Associations of af-SG and cfPWV with age, CVD risk factors (age, BMI, blood pressure, heart rate, glucose and blood lipid levels) and CVD status (hypertension, diabetes, coronary heart disease, heart failure, stroke) were determined using linear and logistic regression analyses. RESULTS: (i) the af-SG and cfPWV demonstrated comparable associations with age and CVD risk factors, except BMI. (ii) a low af-SG was associated with diabetes, coronary heart disease, heart failure and stroke, whilst a high cfPWV was only associated with diabetes. CONCLUSION: Although future studies are necessary to confirm clinical utility, the af-SG is a promising tool that may provide a unique picture of hemodynamic integration and identification of CVD risk when compared with cfPWV.

14.
Clin Chem ; 67(4): 653-661, 2021 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-33582779

RESUMO

INTRODUCTION: Laboratory studies suggest an involvement of growth differentiation factor 15 (GDF-15) in metabolic dysregulation. However, the utility of GDF-15 for assessing risk of cardiometabolic outcomes has not been rigorously examined among older adults. METHODS: We conducted a cross-sectional analysis of older adults who attended visit 6 (2016-2017) of the Atherosclerosis Risk in Communities (ARIC) Study. We used multivariable logistic regression to quantify cross-sectional associations of GDF-15 (in quartiles) with prevalent diabetes, obesity, atherosclerotic cardiovascular disease (ASCVD), subclinical myocardial stress/injury (assessed by NT-proB-type Natriuretic Peptide [NT-proBNP] and high-sensitivity cardiac troponin T [hs-cTnT]), and heart failure (HF). RESULTS: Among 3792 ARIC study participants (mean age 80 years, 59% women, 23% Blacks and 77% Whites, mean GDF-15: 2094.9 pg/mL [SD: 1395.6]), higher GDF-15 concentrations (highest vs. lowest quartile) were positively associated with diabetes (adjusted odds ratio [aOR]:] : 2.48, 95% CI : 1.89, 3.26), ASCVD (aOR: 1.57, 95% CI: 1.16, 2.11), increased hscTnT (aOR: 2.27, 95%CI: 1.54, 3.34), increased NT-proBNP (aOR: 1.98, 95%CI: 1.46, 2.70), and HF (aOR: 3.22, 95%CI : 2.13, 4.85), in models adjusted for demographics and traditional cardiovascular risk factors. CONCLUSIONS: In this sample of older US black and whites, increased GDF-15 was positively associated with diabetes, ASCVD, HF, and markers of subclinical myocardial stress or injury. These results illustrate the diverse aspects of the link between GDF-15 and diseases states, and its potential utility as robust biomarker of adverse cardiometabolic outcomes.

15.
J Am Coll Cardiol ; 77(5): 559-571, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33538254

RESUMO

BACKGROUND: Although intensive blood pressure reduction has cardiovascular benefits, the absolute benefit is greater in those at higher cardiovascular disease (CVD) risk. OBJECTIVES: This study examined whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) helps identify subjects at higher risk for CVD events across systolic blood pressure (SBP), diastolic blood pressure (DBP), or pulse pressure (PP) categories. METHODS: Participants from the ARIC (Atherosclerosis Risk In Communities) study visit 4 (1996 to 98) were grouped according to SBP, DBP, or PP categories and further stratified by NT-proBNP categories. Cox regression models were used to estimate hazard ratios for incident CVD (coronary heart disease, ischemic stroke, or heart failure hospitalization) and mortality across combined NT-proBNP and/or BP categories, adjusting for CVD risk factors. RESULTS: There were 9,309 participants (age: 62.6 ± 5.6 years; 58.3% women) with 2,416 CVD events over a median follow-up of 16.7 years. Within each SBP, DBP, or PP category, a higher category of NT-proBNP (100 to <300 or 300 pg/ml, compared with NT-proBNP <100 pg/ml) was associated with a graded increased risk for CVD events and mortality. Participants with SBP 130 to 139 mm Hg but NT-proBNP ≥300 pg/ml had a hazards ratio of 3.4 for CVD (95% confidence interval: 2.44 to 4.77) compared with a NT-proBNP of <100 pg/ml and SBP of 140 to 149 mm Hg. CONCLUSIONS: Elevated NT-proBNP is independently associated with CVD and mortality across SBP, DBP, and PP categories and helps identify subjects at the highest risk. Participants with stage 1 hypertension but elevated NT-proBNP had greater cardiovascular risk compared with those with stage 2 SBP but lower NT-proBNP. Future studies are needed to evaluate use of biomarker-based strategies for CVD risk assessment to assist with initiation or intensification of BP treatment.

16.
J Am Heart Assoc ; 10(5): e014270, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33586464

RESUMO

Background Antiplatelets, anticoagulants, and statins are commonly prescribed for various indications. The associations between these medications and the risk of intracerebral hemorrhage (ICH) and cerebral microbleeds (CMBs) are unclear. Methods and Results We performed a retrospective study of the ARIC (Atherosclerosis Risk in Communities) study cohort, recruited from 4 US communities in 1987 to 1989 with follow-up. In 2011 to 2013, a subset (N=1942) underwent brain magnetic resonance imaging with CMB evaluation. Time-varying and any antiplatelet, anticoagulant, or statin use was evaluated at subsequent study visits in participants not on each medication at baseline. To determine the hazard of ICH and odds of CMB by medication use, logistic and Cox proportional hazard models were built, respectively, adjusting for the propensity to take the medication, concomitant use of other medications, and cognitive, genetic, and radiographic data. Of 15 719 individuals during up to 20 years of follow-up, 130 participants experienced an ICH. The adjusted hazard of ICH was significantly lower among participants taking an antiplatelet at the most recent study visit before ICH versus nonusers (hazard ratio [HR], 0.53; 95% CI, 0.30-0.92). Statin users had a significantly lower hazard of an ICH compared with nonusers (adjusted HR, 0.13; 95% CI, 0.05-0.34). There was no association of CMB and antiplatelet, anticoagulant, or statin use in adjusted models. Conclusions In this US community-based study, antiplatelet and statin use were associated with lower ICH hazard, whereas no association was noted between CMBs and antiplatelets, anticoagulants, and statins. Further study is needed to understand the differential roles of these medications in cerebral microhemorrhages and macrohemorrhages.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33517414

RESUMO

AIMS : Heart failure increases the risk of kidney disease progression. However, whether cardiac function and structure are associated with the risk of incident chronic kidney disease (CKD) is not well characterized in a community setting. METHODS AND RESULTS : Among 4188 participants (mean age 75 years and 22% blacks) of the Atherosclerosis Risk in Communities Study without prevalent CKD in 2011-13, we examined the association of echocardiographic measures of left ventricular (LV) mass index, ejection fraction, left atrial volume index (LAVi), right ventricular (RV) fractional area change, and peak RV-right atrium (RA) gradient, with the subsequent risk of incident CKD, as defined by >25% decline to estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2, hospitalization with CKD diagnosis, or incident end-stage kidney disease. Multivariable Cox regression models were used to estimate hazard ratios (HRs). The risk of incident CKD was monotonically increased with each of higher LV mass index [adjusted HR 2.61 (1.92-3.55) for highest quartile (Q4) vs. lowest (Q1)], lower ejection fraction [1.54 (1.17-2.04) for Q1 vs. Q4], higher LAVi [2.12 (1.56-2.89) for Q4 vs. Q1], and higher peak RV-RA gradient [2.17 (1.45-3.25) for Q4 vs. Q1] but not with RV function. The associations were consistent between subgroups by sex and race. CONCLUSION : Among community-dwelling older individuals, LV mass index, ejection fraction, LAVi, and peak RV-RA gradient were independently associated with the risk of incident CKD. Our results further support that heart disease is associated with the risk of kidney disease progression and suggest the value of echocardiography for assessing cardiac and kidney health in older populations.

18.
J Am Heart Assoc ; 10(2): e018414, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33399008

RESUMO

Background Acute myocardial infarction (AMI) with in-hospital onset (AMI-IHO) has poor prognosis but is clinically underappreciated. Whether its occurrence has changed over time is uncertain. Methods and Results Since 1987, the ARIC (Atherosclerosis Risk in Communities) study has conducted adjudicated surveillance of AMI hospitalizations in 4 US communities. Our analysis was limited to patients aged 35 to 74 years with symptomatic AMI. Patients with symptoms initiating after hospital arrival were considered AMI-IHO. A total of 26 678 weighted hospitalizations (14 276 unweighted hospitalizations) for symptomatic AMI were identified from 1995 to 2014, with 1137 (4%) classified as in-hospital onset. The population incidence rate of AMI-IHO increased in the 4 ARIC communities from 1995 through 2004 to 2005 through 2014 (12.7-16.9 events per 100 000 people; P for 20-year trend <0.0001), as did the proportion of AMI hospitalizations with in-hospital onset (3.7%-6.1%; P for 20-year trend =0.03). The 10-year proportions were stable for patients aged 35 to 64 years (3.0%-3.4%; P for 20-year trend =0.3) but increased for patients aged ≥65 years (4.6%-7.8%; P for 20-year trend =0.008; P for interaction by age group =0.04). AMI-IHO had a more severe clinical course with lower use of AMI therapies or invasive strategies and higher in-hospital (7% versus 3%), 28-day (19% versus 5%), and 1-year (29% versus 12%) mortality (P<0.0001 for all). Conclusions In this population-based community surveillance, AMI-IHO increased from 2005 to 2014, particularly among older patients. Quality initiatives to improve recognition and management of AMI-IHO should be especially focused on hospitalized patients aged >65.

19.
Arterioscler Thromb Vasc Biol ; 41(3): 1229-1238, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33504178

RESUMO

OBJECTIVE: The aim of this study was to comprehensively assess the association of multiple lipid measures with incident peripheral artery disease (PAD). Approach and Results: We used Cox proportional hazards models to characterize the associations of each of the fasting lipid measures (total cholesterol, LDL-C [low-density lipoprotein cholesterol], HDL-C [high-density lipoprotein cholesterol], triglycerides, RLP-C [remnant lipoprotein cholesterol], LDL-TG [LDL-triglycerides], sdLDL-C [small dense LDL-C], and Apo-E-HDL [Apo-E-containing HDL-C]) with incident PAD identified by pertinent International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) hospital discharge codes (eg, 440.2) among 8330 Black and White ARIC (Atherosclerosis Risk in Communities) participants (mean age 62.8 [SD 5.6] years) free of PAD at baseline (1996-1998) through 2015. Since lipid traits are biologically correlated to each other, we also conducted principal component analysis to identify underlying components for PAD risk. There were 246 incident PAD cases with a median follow-up of 17 years. After accounting for potential confounders, the following lipid measures were significantly associated with PAD (hazard ratio per 1-SD increment [decrement for HDL-C and Apo-E-HDL]): triglycerides, 1.21 (95% CI, 1.08-1.36); RLP-C, 1.18 (1.08-1.29); LDL-TG, 1.18 (1.05-1.33); HDL-C, 1.39 (1.16-1.67); and Apo-E-HDL, 1.27 (1.07-1.51). The principal component analysis identified 3 components (1: mainly loaded by triglycerides, RLP-C, LDL-TG, and sdLDL-C; 2: by HDL-C and Apo-E-HDL; and 3: by LDL-C and RLP-C). Components 1 and 2 showed independent associations with incident PAD. CONCLUSIONS: Triglyceride-related and HDL-related lipids were independently associated with incident PAD, which has implications on preventive strategies for PAD. However, none of the novel lipid measures outperformed conventional ones. Graphic Abstract: A graphic abstract is available for this article.


Assuntos
Lipídeos/sangue , Doença Arterial Periférica/sangue , Idoso , Idoso de 80 Anos ou mais , Apolipoproteínas E/sangue , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Estudos de Coortes , Dislipidemias/sangue , Dislipidemias/complicações , Feminino , Humanos , Lipoproteínas/sangue , Lipoproteínas HDL/sangue , Lipoproteínas LDL/sangue , Masculino , Doença Arterial Periférica/etiologia , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Triglicerídeos/sangue
20.
J Am Soc Nephrol ; 32(3): 629-638, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33510037

RESUMO

BACKGROUND: CKD is associated with sudden cardiac death and atrial fibrillation (AF). However, other types of arrhythmia and different measures of the burden of arrhythmias, such as presence and frequency, have not been well characterized in CKD. METHODS: To quantify the burden of arrhythmias across CKD severity in 2257 community-dwelling adults aged 71-94 years, we examined associations of major arrhythmias with CKD measures (eGFR and albuminuria) among individuals in the Atherosclerosis Risk in Communities study. Participants underwent 2 weeks of noninvasive, single-lead electrocardiogram monitoring. We examined types of arrhythmia burden: presence and frequency of arrhythmias and percent time in arrhythmias. RESULTS: Of major arrhythmias, there was a higher prevalence of AF and nonsustained ventricular tachycardia among those with more severe CKD, followed by long pause (>30 seconds) and atrioventricular block. Nonsustained ventricular tachycardia was the most frequent major arrhythmia (with 4.2 episodes per person-month). Most participants had ventricular ectopy, supraventricular tachycardia, and supraventricular ectopy. Albuminuria consistently associated with higher AF prevalence and percent time in AF, and higher prevalence of nonsustained ventricular tachycardia. When other types of arrhythmic burden were examined, lower eGFR was associated with a lower frequency of atrioventricular block. Although CKD measures were not strongly associated with minor arrhythmias, higher albuminuria was associated with a higher frequency of ventricular ectopy. CONCLUSIONS: CKD, especially as measured by albuminuria, is associated with a higher burden of AF and nonsustained ventricular tachycardia. Additionally, eGFR is associated with less frequent atrioventricular block, whereas albuminuria is associated with more frequent ventricular ectopy. Use of a novel, 2-week monitoring approach demonstrated a broader range of arrhythmias associated with CKD than previously reported.

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