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1.
Diabetes Care ; 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31471378

RESUMO

OBJECTIVE: Experimental studies have implicated soluble (s)CD14, an effector of lipopolysaccharide-induced inflammation, in insulin resistance, but its role in human metabolic endotoxemia has not been studied. We evaluated sCD14 in relation to dysglycemia in older adults and how this compares to other markers of inflammation. RESEARCH DESIGN AND METHODS: We investigated associations of sCD14, interleukin-6 (IL-6), CRP, and white blood cell (WBC) count with insulin resistance (quantitative insulin-sensitivity check index and HOMA 2 of insulin resistance) and incident type 2 diabetes in a population-based cohort of older adults. We also assessed the causal role of sCD14 in insulin resistance using an instrumental variable approach by Mendelian randomization. RESULTS: After adjustment for conventional risk factors, each of the four biomarkers showed positive cross-sectional associations with both insulin resistance measures. These associations persisted after mutual adjustment for all markers except sCD14. Over a median follow-up of 11.6 years, 466 cases of diabetes occurred. All biomarkers except sCD14 were positively associated with diabetes, although only WBC count remained associated (hazard ratio 1.43 per doubling [95% CI 1.07, 1.90]) after mutual adjustment. Instrumental variable analysis did not support a causal role for sCD14 in insulin resistance. CONCLUSIONS: Among older adults, sCD14 was associated with insulin resistance, but this disappeared after adjustment for other biomarkers, showed no evidence of a causal basis, and was not accompanied by a similar association with diabetes. IL-6, CRP, and WBC count were each associated with insulin resistance and diabetes, WBC count most robustly. These findings do not support a central role for sCD14, but highlight the preeminence of WBC count as an inflammatory measure of diabetes risk in this population.

2.
Clin Infect Dis ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31504325

RESUMO

BACKGROUND: HIV may affect the risk of death due to cardiovascular disease (CVD) differently in men versus women. METHODS: We examined CVD mortality rates between 2007 and 2017 among all HIV-positive New York City residents age 13+ by sex, using data from city HIV surveillance and vital statistics and the National Death Index. Residents without HIV were enumerated using modified US intercensal estimates. We determined associations of HIV status with CVD mortality by sex after accounting for age, race/ethnicity, year, and neighborhood poverty, defined as the percent living below the federal poverty level. RESULTS: There were 3,234 CVD deaths reported among 147,915 HIV-positive New Yorkers, with the proportion of deaths due to CVD increasing from 11% in 2007 to 22% in 2017. The age-standardized CVD mortality rate was 2.7/1,000 person-years among both men and women with HIV. The relative rate of CVD mortality associated with HIV status was significantly higher among women (adjusted rate ratio [aRR] 1.7, 95% CI 1.6-1.8) than men (aRR 1.2, 95% CI 1.1-1.3) overall, and within strata defined by neighborhood poverty. Sex differences in CVD mortality rates were the greatest comparing HIV-positive individuals having detectable HIV RNA and CD4+ T-cell counts <500 cells/uL with HIV-negative individuals. CONCLUSIONS: One in five deaths among people with HIV is now associated with CVD. HIV providers should recognize CVD risk among women with HIV, and reinforce preventive measures (e.g., smoking cessation, blood pressure control, lipid management) and viremic control among all people living with HIV to reduce CVD mortality.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31402089

RESUMO

The mitral annulus is a fibrous structure that surrounds the mitral valve leaflets and is prone to calcification. Despite its common occurrence, association with cardiovascular morbidity and mortality and relationship with dysfunction of the mitral valve, the pathobiology of mitral annular calcification is incompletely understood. Mitral annular calcification is no longer regarded as a local, chronic and degenerative process resulting in precipitation of calcium and phosphate, but as an active and regulated molecular process that is related to lipid metabolism, hemodynamic stress, chronic kidney disease, bone and mineral metabolism and inflammation. This review summarizes the current evidence examining the pathophysiologic determinants of mitral annular calcification.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31359766

RESUMO

C1q/tumor necrosis factor (TNF)-related proteins (CTRPs) have been linked to energy homeostasis and vascular health. People with HIV are susceptible to cardiometabolic disease, but the contributions of different CTRPs are unknown. We investigated the associations of HIV and related factors with serum CTRPs, and CTRPs' relationships with cardiometabolic phenotypes. This involved a cross-sectional analysis of participants in the Women's Interagency HIV Study aged ≥35 with (n = 209) and without (n = 92) HIV who underwent carotid ultrasound in 2004-2005 and had stored serum available for measurement of total adiponectin and CTRPs 1, 3, 5, and 9. The Benjamini/Hochberg procedure was used to control the study-wide false-positive rate. HIV-positive women had significantly higher adiponectin than HIV-negative women after adjustment for sociodemographic, behavioral, and clinical variables [beta = 0.29 (95% confidence interval 0.11-0.47)]. Among HIV-positive women, lower CD4 count was associated with higher adiponectin and history of AIDS with higher CTRP9, but these were only nominally significant. There was no relationship between HIV status and CTRP 1, 3, or 5, nor was antiretroviral therapy or viral load associated with any CTRP. In the entire cohort, higher adiponectin was associated with significantly lower fasting glucose and insulin resistance, while higher CTRP5 [beta = -0.02 (-0.033 to -0.007)]-and, at a nominal level, CTRPs 1 and 3-was associated with significantly lower carotid intima-media thickness. In conclusion, in this sample of middle-aged women, HIV serostatus was positively associated with adiponectin, but not CTRPs. In turn, serum adiponectin was inversely associated with glucose dysregulation, whereas CTRP5 was inversely associated with carotid intima-media thickness. Further research is needed to determine CTRPs' role in atherosclerosis.

6.
J Hypertens ; 2019 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-31356403

RESUMO

OBJECTIVE: We studied associations of circulating collagen type I carboxy-terminal telopeptide (ICTP) and procollagen type III N-terminal propeptide (PIIINP) with long-term renal function decline. METHODS: In the Multi-Ethnic Study of Atherosclerosis, we included 2492 participants initially aged 45-84 years and free of clinical cardiovascular disease (CVD), excluding people with estimated glomerular filtration rate (eGFR) less than 60 ml/min per 1.73 m or urine albumin/creatinine (UAC) at least 30 mg/g. The primary outcome in median 9.4-year follow-up was renal function decline (≥30% decline in eGFR between any two exams or incident UAC ≥ 30 mg/g). The associations of baseline plasma ICTP and PIIINP with renal function decline were estimated using Poisson regression, adjusting for baseline variables race/ethnicity, sex, age, and continuous eGFR and UAC, with further adjustment for CVD risk factors and medications. RESULTS: Baseline serum ICTP was 3.27 ±â€Š1.43 µg/l and PIIINP was 5.43 ±â€Š1.85 µg/l. Mean baseline eGFR was 91.5 ±â€Š18.4 ml/min per 1.73 m. Renal function decline occurred in 19.5% during 9.4-year follow-up. The renal function decline outcome was positively associated with serum ICTP and PIIINP: relative incidence density (95% confidence interval) per SD 1.22 (1.11-1.33) and 1.27 (1.16-1.40), respectively. Additional adjustment for other risk factors did not greatly alter findings. CONCLUSION: High collagen biomarker concentrations in serum were associated with future decline in renal function in people initially free of CVD and with normal eGFR, consistent with collagen production signaling renal decline. The continuous association observed for ICTP which, unlike PIIINP, is filtered by the kidney, may owe to its double status as a sensitive marker of glomerular function and collagen degradation.

7.
Am J Hum Genet ; 105(1): 15-28, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31178129

RESUMO

Circulating levels of adiponectin, an adipocyte-secreted protein associated with cardiovascular and metabolic risk, are highly heritable. To gain insights into the biology that regulates adiponectin levels, we performed an exome array meta-analysis of 265,780 genetic variants in 67,739 individuals of European, Hispanic, African American, and East Asian ancestry. We identified 20 loci associated with adiponectin, including 11 that had been reported previously (p < 2 × 10-7). Comparison of exome array variants to regional linkage disequilibrium (LD) patterns and prior genome-wide association study (GWAS) results detected candidate variants (r2 > .60) spanning as much as 900 kb. To identify potential genes and mechanisms through which the previously unreported association signals act to affect adiponectin levels, we assessed cross-trait associations, expression quantitative trait loci in subcutaneous adipose, and biological pathways of nearby genes. Eight of the nine loci were also associated (p < 1 × 10-4) with at least one obesity or lipid trait. Candidate genes include PRKAR2A, PTH1R, and HDAC9, which have been suggested to play roles in adipocyte differentiation or bone marrow adipose tissue. Taken together, these findings provide further insights into the processes that influence circulating adiponectin levels.

8.
Diab Vasc Dis Res ; 16(5): 483-485, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31064218

RESUMO

Carboxymethyl-lysine is an advanced glycation end product that is detectable in the serum. Higher carboxymethyl-lysine levels have been associated with increased risk of coronary heart disease, stroke and cardiovascular mortality. We determined whether high carboxymethyl-lysine levels are also associated with the risk of peripheral artery disease in Cardiovascular Health Study participants who were all aged 65 years and older at baseline. Multivariate Cox proportional hazards models were used to determine the association of baseline carboxymethyl-lysine levels with incident peripheral artery disease in 3267 individuals followed for a median length of 10.0 years. A total of 157 cases of incident peripheral artery disease occurred during follow-up. No significant relationship between carboxymethyl-lysine and risk of peripheral artery disease was found (hazard ratio per standard deviation increment = 1.03; 95% confidence interval = 0.87, 1.23).

9.
Atherosclerosis ; 285: 79-86, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31048102

RESUMO

BACKGROUND AND AIMS: Previous research has implicated dysregulation of phosphate metabolism and calcium-phosphate solubilization in cardiovascular calcification, but epidemiologic studies evaluating longitudinal associations with valvular or annular calcification by computed tomography (CT), a highly sensitive imaging modality, are lacking. Our primary aim was to investigate the associations of mineral biomarkers with incidence and progression of aortic valve calcification (AVC) and mitral annular calcification (MAC). METHODS: We evaluated the associations of serum FGF-23 (n = 6547 participants), phosphate (n = 6547), and fetuin-A (n = 2550) measured at baseline in the community-based Multi-Ethnic Study of Atherosclerosis with AVC and MAC on CT performed at baseline and at a median of 2.4 (1.6, 3.1) years later. We used linear mixed-effects models to account simultaneously for prevalence, incidence and progression of AVC and MAC. RESULTS: After adjustment for demographic and clinical characteristics, a significant association was documented for FGF-23 with accelerated annual progression of MAC (2.83 Agatston units (AU), 95% CI = 0.49, 5.17 AU, per standard deviation (18.46 pg/mL) of FGF-23), but this was not seen for phosphate or fetuin-A. None of these biomarkers was associated with accelerated annual progression of AVC. CONCLUSIONS: This study provides evidence relating serum FGF-23 to accelerated annual MAC progression. Whether this mineral regulator is a risk marker or is involved in pathogenesis merits further investigation.

10.
Ann Thorac Surg ; 108(3): 756-763, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30980824

RESUMO

BACKGROUND: Hemolysis, even at low levels, activates platelets to create a prothrombotic state and is common during mechanical circulatory support. We examined the association of low-level hemolysis (LLH) and nonhemorrhagic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support. METHODS: A single-center retrospective review of all adult patients placed on VA ECMO from January 2012 to September 2017 was conducted. To determine the association between LLH and nonhemorrhagic stroke, patients were categorized as those with and without LLH. LLH was defined by 48-hour plasma free hemoglobin (PFHb) of 11 to 50 mg/dL after VA ECMO implantation. RESULTS: Of 201 patients who underwent VA ECMO placement, 150 (75%) met inclusion criteria and comprised the study population. They were 55 ± 14 years of age and 50 (33%) were women. Sixty-two (41%) patients had LLH. Patients with LLH had a higher likelihood of incident nonhemorrhagic stroke during VA ECMO support (20 [32%] versus 4 [5%]; adjusted hazard ratio [HR], 7.6; 95% confidence interval [CI], 2.2 to 25.9; p = 0.001). The severity of LLH was associated with an incrementally higher likelihood of a nonhemorrhagic stroke (PFHb 26 to 50 mg/dL: HR, 11.3; 95% CI, 3.6 to 35.1; p = 0.001; PFHb 11 to 25 mg/dL: HR, 4.4; 95% CI, 1.36 to 14.85; p = 0.014) in comparison with no LLH. Those with LLH had a 2-fold greater increase in mean platelet volume after VA ECMO placement (0.98 ± 1.1 fL versus 0.49 ± 0.96 fL; p = 0.03). Patients with a nonhemorrhagic stroke had a higher operative mortality (20 [83%] versus 57 [45%]; adjusted HR, 3.1; 95% CI, 1.8 to 5.3; p < 0.001). CONCLUSIONS: Hemolysis at low levels during VA ECMO support is associated with subsequent nonhemorrhagic stroke.

11.
AIDS ; 33(6): 1043-1052, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30946158

RESUMO

OBJECTIVE: To evaluate plasma acylcarnitine profiles and their relationships with progression of carotid artery atherosclerosis among individuals with and without HIV infection. DESIGN: Prospective cohort studies of 499 HIV-positive and 206 HIV-negative individuals from the Women's Interagency HIV Study and the Multicenter AIDS Cohort Study. METHODS: Twenty-four acylcarnitine species were measured in plasma samples of participants at baseline. Carotid artery plaque was assessed using repeated B-mode carotid artery ultrasound imaging in 2004-2013. We examined the associations of individual and aggregate short-chain (C2-C7), medium-chain (C8-C14) and long-chain acylcarnitines (C16-C26) with incident carotid artery plaque over 7 years. RESULTS: Among 24 acylcarnitine species, C8-carnitines and C20 : 4-carnitines showed significantly lower levels comparing HIV-positive to HIV-negative individuals (false discovery rate adjusted P < 0.05); and C20-carnitines and C26-carnitines showed significantly higher levels in HIV positive using antiretroviral therapy than those without antiretroviral therapy (false discovery rate adjusted P < 0.05). In the univariate analyses, higher aggregated short-chain and long-chain acylcarnitine scores were associated with increased risk of carotid artery plaque [risk ratios (RRs) = 1.22 (95% confidence interval 1.02-1.45) and 1.20 (1.02-1.41) per SD increment, respectively]. The association for the short-chain acylcarnitine score remained significant [RR = 1.23 (1.05-1.44)] after multivariate adjustment (including traditional cardiovascular disease risk factors). This association was more evident in HIV-positive individuals without persistent viral suppression [RR = 1.37 (1.11-1.69)] compared with those with persistent viral suppression during follow-up [RR = 1.03 (0.76-1.40)] or HIV-negative individuals [RR = 1.02 (0.69-1.52)]. CONCLUSION: In two HIV cohorts, plasma levels of most acylcarnitines were not significantly different between HIV-positive and HIV-negative individuals. However, higher levels of aggregated short-chain acylcarnitines were associated with progression of carotid artery atherosclerosis.

12.
ASAIO J ; 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30973402

RESUMO

Fibrinogen is a clotting factor and a major determinant of platelet aggregation. Albumin, on the other hand, inhibits platelet function and thrombus formation. Taken together, an elevated fibrinogen albumin ratio (FAR) has been described as a marker of disease severity during prothrombotic conditions. We evaluated the association of FAR and ischemic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support. A single center, retrospective study was performed including all adult patients placed on VA ECMO. FAR was calculated from fibrinogen and albumin measurements in the first 24 hours of VA-ECMO initiation. Patients were categorized into high (≥125) and low (<125) FAR groups and the risk of eventual ischemic stroke was determined. There were 201 patients who underwent VA ECMO placement and 157 had a FAR. They were 56 ± 14 years old and 66 (42%) had a high FAR. Patients with a high FAR had lower survival free from an ischemic stroke during VA ECMO (log rank p < 0.001; adjusted hazard ratio 5.51; 95% CI: 1.8-16.5). In tertile analysis, the level of FAR was associated with an incrementally higher likelihood of eventual ischemic stroke (log rank p = 0.004). Those with a high FAR had greater mean platelet volume (10.8[10.4-12] vs. 10.5[10.2-11.9]fl, p = 0.004). An elevated FAR during the first 24 hours of VA ECMO placement is associated with a greater risk of a subsequent ischemic stroke. Our findings suggest that assessment of FAR soon after VA ECMO placement may assist with early stratification of patients at risk for an ischemic stroke.

13.
J Am Heart Assoc ; 8(8): e012250, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30957681

RESUMO

Background Hypertrophic cardiomyopathy is defined as unexplained left ventricular ( LV ) hypertrophy (wall thickness ≥15 mm) and is prevalent in 0.2% of adults (1:500) in population-based studies using echocardiography. Cardiac magnetic resonance imaging ( MRI ) allows for more accurate wall thickness measurement across the entire ventricle than echocardiography. The prevalence of unexplained LV hypertrophy by cardiac MRI is unknown. MESA (Multi-Ethnic Study of Atherosclerosis) recruited individuals without overt cardiovascular disease 45 to 84 years of age. Methods and Results We studied 4972 individuals who underwent measurement of regional LV wall thickness by cardiac MRI as part of the MESA baseline exam. American Heart Association criteria were used to define LV segments. We excluded participants with hypertension, LV dilation (≥95% predicted end-diastolic volume) or dysfunction (ejection fraction ≤50%), moderate-to-severe left-sided valve lesions by cardiac MRI , severe aortic valve calcification by cardiac computed tomography (aortic valve Agatston calcium score >1200 in women or >2000 in men), obesity (body mass index >35 kg/m2), diabetes mellitus, and current smoking. Sixty-seven participants (aged 64±10 years, 9% female) had unexplained LV hypertrophy (wall thickness ≥15 mm in at least 2 adjacent LV segments), representing 1.4% (1 in 74) participants, 2.6% of men and 0.2% of women. Prevalence was similar across categories of race/ethnicity. Hypertrophy was focal in 17 (25.4%), intermediate in 44 (65.7%), and diffuse in 5 (7.5%) participants. Conclusions The prevalence of unexplained LV hypertrophy in a population-based cohort using cardiac MRI was 1.4%. This may have implications for the diagnosis of patients with hypertrophic cardiomyopathy and will require further study.

14.
Circ Cardiovasc Imaging ; 12(2): e008513, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30712363

RESUMO

BACKGROUND: Mitral annular calcification (MAC) is associated with cardiovascular events and mitral valve dysfunction. However, the underlying pathophysiology remains incompletely understood. In this prospective longitudinal study, we used a multimodality approach including positron emission tomography, computed tomography, and echocardiography to investigate the pathophysiology of MAC and assess factors associated with disease activity and progression. METHODS: A total of 104 patients (age 72±8 years, 30% women) with calcific aortic valve disease, therefore predisposed to MAC, underwent 18F-sodium fluoride (calcification activity) and 18F-Fluorodeoxyglucose (inflammation activity) positron emission tomography, computed tomography calcium scoring, and echocardiography. Sixty patients underwent repeat computed tomography and echocardiography after 2 years. RESULTS: MAC (mitral annular calcium score >0) was present in 35 (33.7%) patients who had increased 18F-fluoride (tissue-to-background ratio, 2.32 [95% CI, 1.81-3.27] versus 1.30 [1.22-1.49]; P<0.001) and 18F-Fluorodeoxyglucose activity (tissue-to-background ratio, 1.44 [1.37-1.58] versus 1.17 [1.12-1.24]; P<0.001) compared with patients without MAC. MAC activity (18F-fluoride uptake) was closely associated with the local calcium score and 18F-Fluorodeoxyglucose uptake, as well as female sex and renal function. Similarly, MAC progression was closely associated with local factors, in particular, baseline MAC. Traditional cardiovascular risk factors and calcification activity in bone or remote atherosclerotic areas were not associated with disease activity nor progression. CONCLUSIONS: MAC is characterized by increased local calcification activity and inflammation. Baseline MAC burden was associated with disease activity and the rate of subsequent progression. This suggests a self-perpetuating cycle of calcification and inflammation that may be the target of future therapeutic interventions.

16.
J Am Heart Assoc ; 8(3): e010855, 2019 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-30691334

RESUMO

Background Although admission heart rate predicts higher mortality after acute myocardial infarction ( AMI ), less is known about discharge heart rate. We tested the hypothesis that higher discharge heart rate after AMI is related to increased long-term mortality independent of admission heart rate, and assessed whether ß blockers modify this relationship. Methods and Results In 2 prospective US multicenter registries of AMI , we evaluated the associations of discharge and admission heart rate with 3-year mortality using Cox models. Among 6576 patients with AMI , discharge heart rate was modestly associated with initial heart rate ( r=0.28), comorbidities, and infarct severity. In this cohort, 10.7% did not receive ß blockers at discharge. After full adjustment for demographic, psychosocial, and clinical covariates, discharge heart rate (hazard ratio [HR]=1.14 per 10 beats per minute [bpm]; 95% CI =1.07-1.21 per 10 bpm) was more strongly associated with risk of death than admission heart rate (HR=1.05 per 10 bpm; 95% CI=1.02-1.09 per 10 bpm) when both were entered in the same model ( P=0.043 for comparison). There was a significant interaction between discharge heart rate and ß-blocker use ( P=0.004) on mortality, wherein risk of death was markedly higher among those with high discharge heart rate and not on ß blockers (HR=1.35 per 10 bpm; 95% CI=1.19-1.53 per 10 bpm) versus those with a high discharge heart rate and on ß blockers at discharge (HR=1.10 per 10 bpm; 95% CI=1.03-1.17 per 10 bpm). Conclusions Higher discharge heart rate after AMI was more strongly associated with 3-year mortality than admission heart rate, and the risk associated with higher discharge heart rate was modified by ß blockers at discharge. These findings highlight opportunities for risk stratification and intervention that will require further investigation.

17.
EBioMedicine ; 37: 392-400, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30366816

RESUMO

BACKGROUND: Gut microbiota alteration has been implicated in HIV infection and metabolic disorders. The relationship between gut microbiota and diabetes has rarely been studied in HIV-infected individuals, who have excess risk of metabolic disorders. METHODS: Our study during 2015-2016 enrolled predominantly African Americans and Hispanics in the Women's Interagency HIV Study. We studied 28 women with long-standing HIV infection under antiretroviral therapy and 20 HIV-uninfected, but at high risk of infection, women (16 HIV+ and 6 HIV- with diabetes). Fecal samples were analyzed by sequencing prokaryotic16S rRNA gene. Plasma metabolomics profiling was performed by liquid chromatography-tandem mass spectrometry. FINDINGS: No significant differences in bacterial α- or ß-diversity were observed by diabetes or HIV serostatus (all P > .1). Relative abundances of four genera (Finegoldia, Anaerococcus, Sneathia, and Adlercreutzia) were lower in women with diabetes compared to those without diabetes (all P < .01). In women with diabetes, plasma levels of several metabolites in tryptophan catabolism (e,g., kynurenine/tryptophan ratio), branched-chain amino acid and proline metabolism pathways were higher, while glycerophospholipids were lower (all P < .05). Results were generally consistent between HIV-infected and HIV-uninfected women, and no significant modification effects by HIV serostatus were observed (all Pinteraction > 0.05). Anaerococcus, known to produce butyrate which is involved in anti-inflammation and glucose metabolism, showed an inverse correlation with kynurenine/tryptophan ratio (r = -0.38, P < .01). INTERPRETATION: Among women with or at high risk for HIV infection, diabetes is associated with gut microbiota and plasma metabolite alteration, including depletion of butyrate-producing bacterial population along with higher tryptophan catabolism. FUND: NHLBI (K01HL129892, R01HL140976) and FMF.

18.
Circ Arrhythm Electrophysiol ; 11(10): e006557, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30354407

RESUMO

BACKGROUND: Atrial fibrosis is a hallmark of structural remodeling in atrial fibrillation (AF). Plasma procollagen type III N-terminal propeptide (PIIINP) reflects collagen synthesis and degradation while collagen type I carboxy-terminal telopeptide (ICTP) reflects collagen degradation. We aimed to study baseline plasma PIIINP and ICTP and their associations with incident AF in participants initially free of overt cardiovascular disease. METHODS: In a stratified sample of the Multi-Ethnic Study of Atherosclerosis, initially aged 45-84 years, 3071 participants had both PIIINP and ICTP measured at baseline. Incident AF in 10-year follow-up was based on a hospital International Classification of Diseases code for AF or atrial flutter, in- or outpatient Medicare claims through 2011 (primarily in those aged 65-84 years), or ECG 10 years after baseline (n=357). The associations of PIIINP and ICTP with incident AF were estimated using Poisson regression with follow-up time offset. RESULTS: Baseline PIIINP (5.50±1.55 µg/L) and ICTP (mean±SD, 3.41±1.37 µg/L) were positively related (both P<0.0001) to incident AF in a model adjusting for age, race/ethnicity, and sex, with an apparent threshold (relative incidence density 2.81 [1.94-4.08] for PIIINP ≥8.5 µg/L [3.5% of the sample] and 3.46 [2.36-5.07] for ICTP ≥7 µg/L [1.7% of the sample]). Findings were attenuated but remained statistically significant after further adjustment for systolic blood pressure, height, body mass index, smoking, and renal function. Additional adjustment for other risk factors and biomarkers of inflammation did not alter conclusions. CONCLUSIONS: Plasma collagen biomarkers, particularly at elevated levels, were associated with excess risk for AF.

19.
Int J Cardiol ; 272: 323-328, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30082119

RESUMO

BACKGROUND: Patients with chronic kidney disease are at increased risk of cardiovascular disease (CVD). Even after kidney transplant, the rate of CVD events and death remain elevated. Early detection of patients at risk would be helpful for guiding aggressive preventive therapy. The purpose of this study was to evaluate global longitudinal strain (GLS) as a predictor of CVD events and death after kidney transplant. METHOD: Among patients with successful kidney transplant between 3/2009 and 12/2012 at our institution, 111 individuals had an echocardiogram within 6 months of the transplant. Medical records were evaluated for demographics and patient characteristics. Echocardiograms were analyzed for conventional measurements, and GLS was assessed using speckle-tracking analysis. RESULTS: The median age of the study sample was 54 years. Overall, 60% were men; 35% were non-Hispanic black, and 50% Hispanic. After a mean follow-up of 3.8 ±â€¯0.5 years, there were 21 cardiovascular events or deaths. Patients who experienced an event were older, more frequently had a history of coronary artery disease, and had higher LV filling/longitudinal diastolic annular velocity (E/e') than those who did not. GLS was significantly associated with event-free survival even after adjusting for age, sex, race-ethnicity, hypertension, diabetes, history of coronary artery disease or heart failure, and E/e'. CONCLUSION: Reduced GLS peri-transplant is significantly associated with increased CVD events or death after kidney transplant. Larger studies are required to determine the incremental predictive value of GLS over clinical and other echocardiographic parameters for adverse CVD events following renal transplantation.

20.
Diabetes Care ; 41(9): 1901-1908, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-30002202

RESUMO

OBJECTIVE: To investigate the relationship of osteocalcin (OC), a marker of bone formation, and C-terminal cross-linked telopeptide of type I collagen (CTX), a marker of bone resorption, with incident diabetes in older women. RESEARCH DESIGN AND METHODS: The analysis included 1,455 female participants from the population-based Cardiovascular Health Study (CHS) (mean [SD] age 74.6 [5.0] years). The cross-sectional association of serum total OC and CTX levels with insulin resistance (HOMA-IR) was examined using multiple linear regression. The longitudinal association of both markers with incident diabetes, defined by follow-up glucose measurements, medications, and ICD-9 codes, was examined using multivariable Cox proportional hazards models. RESULTS: OC and CTX were strongly correlated (r = 0.80). In cross-sectional analyses, significant or near-significant inverse associations with HOMA-IR were observed for continuous levels of OC (ß = -0.12 per SD increment; P = 0.004) and CTX (ß = -0.08 per SD; P = 0.051) after full adjustment for demographic, lifestyle, and clinical covariates. During a median follow-up of 11.5 years, 196 cases of incident diabetes occurred. After full adjustment, both biomarkers exhibited inverse associations with incident diabetes (OC: hazard ratio 0.85 per SD [95% CI 0.71-1.02; P = 0.075]; CTX: 0.82 per SD [0.69-0.98; P = 0.031]), associations that were comparable in magnitude and approached or achieved statistical significance. CONCLUSIONS: In late postmenopausal women, lower OC and CTX levels were associated with similarly increased risks of insulin resistance at baseline and incident diabetes over long-term follow-up. Further research to delineate the mechanisms linking abnormal bone homeostasis and energy metabolism could uncover new approaches for the prevention of these age-related disorders.


Assuntos
Biomarcadores/sangue , Remodelação Óssea/fisiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Reabsorção Óssea/sangue , Reabsorção Óssea/epidemiologia , Osso e Ossos/metabolismo , Sistema Cardiovascular/fisiopatologia , Colágeno Tipo I/sangue , Estudos Transversais , Feminino , Humanos , Incidência , Osteocalcina/sangue , Fatores de Risco
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