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1.
Small ; : e1801503, 2018 Jun 27.
Article in English | MEDLINE | ID: mdl-29952107

ABSTRACT

Dip-pen nanolithography (DPN) is used to precisely position core/thick-shell ("giant") quantum dots (gQDs; ≥10 nm in diameter) exclusively on top of silicon nanodisk antennas (≈500 nm diameter pillars with a height of ≈200 nm), resulting in periodic arrays of hybrid nanostructures and demonstrating a facile integration strategy toward next-generation quantum light sources. A three-step reading-inking-writing approach is employed, where atomic force microscopy (AFM) images of the pre-patterned substrate topography are used as maps to direct accurate placement of nanocrystals. The DPN "ink" comprises gQDs suspended in a non-aqueous carrier solvent, o-dichlorobenzene. Systematic analyses of factors influencing deposition rate for this non-conventional DPN ink are described for flat substrates and used to establish the conditions required to achieve small (sub-500 nm) feature sizes, namely: dwell time, ink-substrate contact angle and ink volume. Finally, it is shown that the rate of solvent transport controls the feature size in which gQDs are found on the substrate, but also that the number and consistency of nanocrystals deposited depends on the stability of the gQD suspension. Overall, the results lay the groundwork for expanded use of nanocrystal liquid inks and DPN for fabrication of multi-component nanostructures that are challenging to create using traditional lithographic techniques.

2.
Circulation ; 132(10): 916-22, 2015 Sep 08.
Article in English | MEDLINE | ID: mdl-26224808

ABSTRACT

BACKGROUND: In the general population, the majority of cardiovascular events occur in people at the low to moderate end of population risk distribution. The 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol recommends consideration of statin therapy for adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5% based on traditional risk factors. Whether use of nontraditional risk markers can improve risk assessment in those below this threshold for statin therapy is unclear. METHODS AND RESULTS: Using data from the Multi-Ethnic Study of Atherosclerosis (MESA), a population sample free of clinical CVD at baseline, we calibrated the Pooled Cohort Equations (cPCE). ASCVD was defined as myocardial infarction, coronary heart disease death, or fatal or nonfatal stroke. Adults with an initial cPCE <7.5% and elevated levels of additional risk markers (abnormal test) whose new calculated risk was ≥7.5% were considered statin eligible: low-density lipoprotein cholesterol ≥160 mg/dL; family history of ASCVD; high-sensitivity C-reactive protein ≥2 mg/dL; coronary artery calcium score ≥300 Agatston units or ≥75th percentile for age, sex, and ethnicity; and ankle-brachial index <0.9. We compared the absolute and relative ASCVD risks among those with versus without elevated posttest estimated risk. We calculated the number needed to screen to identify 1 person with abnormal test for each risk marker, defined as the number of participants with baseline cPCE risk <7.5% divided by the number with an abnormal test reclassified as statin eligible. Of 5185 participants not taking statins with complete data (age, 45-84 years), 4185 had a cPCE risk <7.5%. During 10 years of follow-up, 57% of the ASCVD events (183 of 320) occurred among adults with a cPCE risk <7.5%. When people with diabetes mellitus were excluded, the coronary artery calcium criterion reclassified 6.8% upward, with an event rate of 13.3%, absolute risk of 10%, relative risk of 4.0 (95% confidence interval [CI], 2.8-5.7), and number needed to screen of 14.7. The corresponding numbers for family history of ASCVD were 4.6%, 15.1%, 12%, 4.3 (95% CI, 3.0-6.4), and 21.8; for high-sensitivity C-reactive protein criteria, 2.6%, 10%, 6%, 2.6 (95% CI, 1.4-4.8), and 39.2; for ankle-brachial index criteria, 0.6%, 9%, 5%, 2.3 (95% CI, 0.6-8.6), and 176.5; and for low-density lipoprotein cholesterol criteria, 0.5%, 5%, 1%, 1.2 (95% CI, 0.2-8.4), and 193.3, respectively. Of the 3882 with <7.5% cPCE risk, 431 (11.1%) were reclassified to ≥7.5% (statin eligible) by at least 1 of the additional risk marker criteria. CONCLUSIONS: In this generally low-risk population sample, a large proportion of ASCVD events occurred among adults with a 10-year cPCE risk <7.5%. We found that the coronary artery calcium score, high-sensitivity C-reactive protein, family history of ASCVD, and ankle-brachial index recommendations by the American College of Cardiology/American Heart Association cholesterol guidelines (Class IIB) identify small subgroups of asymptomatic population with a 10-year cPCE risk <7.5% but with observed ASCVD event rates >7.5% who may warrant statin therapy considerations.


Subject(s)
American Heart Association , Atherosclerosis/blood , Cardiology/standards , Cholesterol/blood , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Practice Guidelines as Topic/standards , Aged , Aged, 80 and over , Atherosclerosis/diagnosis , Atherosclerosis/epidemiology , Biomarkers/blood , Cohort Studies , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Prospective Studies , Risk Factors , United States/epidemiology
3.
J Electrocardiol ; 49(4): 530-5, 2016.
Article in English | MEDLINE | ID: mdl-27222360

ABSTRACT

BACKGROUND: Temporary-permanent pacemakers [TPPM] are externally placed permanent generators attached to active fixation transvenous leads. TPPM can be used as an alternative to standard temporary pacing leads when placement of a permanent pacemaker is contraindicated. We sought to determine the incidence and risk factors for early (within 6months) mortality after placement of a TPPM. METHODS: Electronic medical records were used to extract baseline characteristics for 152 patients from Wake Forest Baptist Medical Center who had a TPPM placed between the years 2007 and 2012. Multivariable adjusted Cox proportional hazard models were used to estimate hazard ratios [HR] and 95% confidence intervals [C]) for baseline characteristics [age, sex, race, hypertension, diabetes, heart failure, coronary artery disease, smoking, dyslipidemia, chronic kidney disease [CKD], and indication for pacemaker] on early mortality. RESULTS: Of the 152 patients [mean age 68.9years; 57.2% female; 86.8% white], 45 [29.6%] died within the first 6months after TPPM placement. No deaths occurred as a direct result of TPPM placement, and only 1 patient experienced documented non-fatal complications. Maximum time to PPM from the date of insertion of TPPM was 336days. Using a backward multivariable adjusted hazard regression model, independent risk factors for early mortality were pre-existing CKD [HR (95% CI): 2.240 (1.002-5.010) for eGFR 30-59 and 7.645 (3.594-16.263) for eGFR <30 compared to eGFR >60] and history of smoking [HR (95% CI): 2.015 (1.099-3.696)]. Surprisingly, dyslipidemia was protective of early mortality [HR (95%CI): 0.470 (0.240-0.924)]. CONCLUSION: TPPM placement is a safe procedure with rare direct complications. CKD and smoking are predictive of increased risk for early mortality in patients undergoing TPPM placement.


Subject(s)
Arrhythmias, Cardiac/mortality , Arrhythmias, Cardiac/prevention & control , Cardiac Pacing, Artificial/mortality , Pacemaker, Artificial/statistics & numerical data , Renal Insufficiency, Chronic/mortality , Smoking/mortality , Age Distribution , Aged , Cardiac Pacing, Artificial/statistics & numerical data , Causality , Comorbidity , Female , Humans , Incidence , Longitudinal Studies , Male , North Carolina/epidemiology , Prosthesis Implantation/statistics & numerical data , Retrospective Studies , Risk Factors , Sex Distribution , Survival Rate , Treatment Outcome
4.
J Electrocardiol ; 47(2): 264-71, 2014.
Article in English | MEDLINE | ID: mdl-24406207

ABSTRACT

BACKGROUND: A widened electrocardiographic spatial QRS-T angle has been shown to be predictive of cardiovascular disease in HIV-infected individuals. However, determinants and risk factors of developing widened QRS-T angle over time in this population remain unknown. METHODS AND RESULTS: Spatial QRS-T angle was automatically measured from standard electrocardiogram of 1444 HIV-infected individuals without baseline widened spatial QRS-T angle from the Strategies for Management of Antiretroviral Therapy [SMART], a clinical trial comparing two antiretroviral treatment strategies [Drug Conservation (DC) vs. Viral Suppression (VS)]. Conditional logistic regression analysis was used to examine the association between baseline characteristics and incident widened spatial QRS-T angle (a new angle>93° in males and>74° in females). During 2544 person-years of follow-up, 199 participants developed widened angle at a rate of 7.8 per 100 person-years. In unadjusted models, female sex, black race (vs. white), DC treatment strategy, current and past smokers (vs. never), history of alcohol abuse, greater body mass index, history of diabetes and higher levels of hs-C-reactive protein were associated with incident widened spatial QRS-T angle. When these variables were entered together in the same model with adjustment for demographics and treatment strategy, DC treatment strategy [OR (95% CI): 1.50 (1.09, 2.07)], female gender [1.69 (1.17, 2.45)], current and past smoking (vs. never) [2.49 (1.63, 3.81) and 1.93 (1.21, 3.09), respectively], and diabetes [2.28 (1.33, 3.91)] predicted incident widened spatial QRS-T angle. CONCLUSIONS: Drug conservation treatment strategy, female gender, smoking, and diabetes are independently predictive of incident widened spatial QRS-T angle in HIV-infected individuals.


Subject(s)
Anti-HIV Agents/therapeutic use , Arrhythmias, Cardiac/physiopathology , Electrocardiography , HIV Infections/drug therapy , HIV Infections/physiopathology , Heart Conduction System/physiopathology , Adult , C-Reactive Protein/metabolism , Female , Humans , Male , Risk Factors , Sex Factors , Smoking/adverse effects
5.
Int J Biol Macromol ; 253(Pt 8): 127479, 2023 Dec 31.
Article in English | MEDLINE | ID: mdl-37866574

ABSTRACT

The primary objective of this investigation was to synthesize a novel antibacterial nanocomposite consisting of natural gellan gum (GG) hydrogel, MnFe LDH, GO, and Fe3O4 nanoparticle, which was developed to adsorb Indigo carmine (IC). The GG hydrogel/MnFe LDH/GO/Fe3O4 nanocomposite was characterized through different analytical, microscopic, and biological methods. The results of adsorption experiments reveal that 0.004 g of the nanocomposite can remove 98.38 % of IC from a solution with an initial concentration of 100 mg/L, within 1 h at room temperature and under acidic pH conditions. Moreover, the nanocomposite material effectively suppressed the in vitro growth of both E. coli and S. aureus strains, with inhibitory rates of 62.33 % and 53.82 %, respectively. The isotherm data obtained in this investigation were fitted by linear and non-linear forms of Langmuir, Freundlich, and Dubinin-Radushkevich (D-R) isotherms equations. The results of the adsorption kinetics study indicated that the pseudo-second-order model best described the experimental data. The findings of this study suggest that the synthesized nanocomposites hold great potential as effective adsorbents for removing IC and bacteria from aqueous solutions.


Subject(s)
Nanocomposites , Water Pollutants, Chemical , Water , Indigo Carmine/chemistry , Adsorption , Hydrogels , Escherichia coli , Staphylococcus aureus , Hydroxides , Magnetic Phenomena , Kinetics , Water Pollutants, Chemical/chemistry , Hydrogen-Ion Concentration , Nanocomposites/chemistry
6.
J Am Heart Assoc ; 10(15): e020157, 2021 08 03.
Article in English | MEDLINE | ID: mdl-34325516

ABSTRACT

Background Atrial fibrillation is associated with increased stroke risk; available risk prediction tools have modest accuracy. We hypothesized that circulating stroke risk biomarkers may improve stroke risk prediction in atrial fibrillation. Methods and Results The REGARDS (Reasons for Geographic and Racial Differences in Stroke) study is a prospective cohort study of 30 239 Black and White adults age ≥45 years. A nested study of stroke cases and a random sample of the cohort included 175 participants (63% women, 37% Black adults) with baseline atrial fibrillation and available blood biomarker data. There were 81 ischemic strokes over 5.2 years in these participants. Adjusted for demographics, stroke risk factors, and warfarin use, the following biomarkers were associated with stroke risk (hazard ratio [HR]; 95% CI for upper versus lower tertile): cystatin C (3.16; 1.04-9.58), factor VIII antigen (2.77; 1.03-7.48), interleukin-6 (9.35; 1.95-44.78), and NT-proBNP (N-terminal B-type natriuretic peptide) (4.21; 1.24-14.29). A multimarker risk score based on the number of blood biomarkers in the highest tertile was developed; adjusted HRs of stroke for 1, 2, and 3+ elevated blood biomarkers, compared with none, were 1.75 (0.57-5.40), 4.97 (1.20-20.5), and 9.51 (2.22-40.8), respectively. Incorporating the multimarker risk score to the CHA2DS2VASc score resulted in a net reclassification improvement of 0.34 (95% CI, 0.04-0.65). Conclusions Findings in this biracial cohort suggested the possibility of substantial improvement in stroke risk prediction in atrial fibrillation using blood biomarkers or a multimarker risk score.


Subject(s)
Atrial Fibrillation/blood , Biomarkers/blood , Decision Support Techniques , Ischemic Stroke/blood , Black or African American , Aged , Aged, 80 and over , Atrial Fibrillation/diagnosis , Atrial Fibrillation/ethnology , Atrial Fibrillation/therapy , Case-Control Studies , Cystatin C/analysis , Factor VIII/analysis , Female , Humans , Incidence , Interleukin-6/blood , Ischemic Stroke/diagnosis , Ischemic Stroke/ethnology , Ischemic Stroke/prevention & control , Male , Middle Aged , Natriuretic Peptide, Brain/blood , Peptide Fragments/blood , Predictive Value of Tests , Prognosis , Proof of Concept Study , Prospective Studies , Risk Assessment , Risk Factors , United States/epidemiology , White People
7.
J Am Chem Soc ; 131(2): 424-5, 2009 Jan 21.
Article in English | MEDLINE | ID: mdl-19113854

ABSTRACT

The controllable synthesis of semiconductor nanocrystals is important for exploiting their size-dependent properties in a variety of applications. The important wide-bandgap semiconductors ZnS and ZnSe crystallize in both the zincblende (ZB) and wurtzite (WZ) structures. While the ZB polymorphs are most stable, methods exist for synthesizing the WZ-type nanocrystals. However, because of the subtle structural differences between the ZB and WZ structures, subtle synthetic differences can favor one polymorph over the other. It is therefore challenging to predictably generate the WZ polymorphs and understand the factors that play a key role in their formation. Through careful mechanistic studies, we show that ZnO nanoparticles, which adopt the WZ structure, form as intermediates in typical reactions that generate WZ-ZnS. This implies that ZnO nanoparticles can serve as structural templates for the preferential formation of WZ-ZnS nanoparticles, and this is confirmed experimentally. Similar chemistry can be used to preferentially form WZ-ZnSe and ZB-ZnSe.

8.
Heart Rhythm ; 16(5): 686-693, 2019 05.
Article in English | MEDLINE | ID: mdl-31036248

ABSTRACT

BACKGROUND: Hispanics/Latinos represent the largest ethnic minority group in the United States. Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States. OBJECTIVE: The purpose of this study was to provide data on the prevalence of AF and its correlates in a representative Hispanic/Latino population-based sample inclusive of all background groups. METHODS: Hispanic Community Health Study/Study of Latinos participants (n=16,415; 60% women; 59% age >45 years) were enrolled between March 2008 and June 2011, representing individuals of Cuban, Dominican, Mexican, Puerto Rican, Central American, and South American heritage. AF was defined by the 12-lead electrocardiogram and/or participant self-report of a physician diagnosis. Hispanic background-specific AF prevalence rates were determined. Weighted sequential logistic regression models were adjusted for demographic factors (age and sex) and clinical variables (diabetes, hypertension, body mass index, tobacco use, and estimated glomerular filtration rate). RESULTS: The overall weighted prevalence of AF was 1.0% (n=162), with the highest prevalence in Hispanics of Dominican and Puerto Rican backgrounds (1.9% and 2.5% respectively) and the lowest in those of Mexican background (0.3%). Diabetes, hypertension, renal disease, left ventricular hypertrophy determined by the electrocardiogram, alcohol use, and English language preference (greater acculturation) (P < .01 for all) were significantly associated with higher AF prevalence. Multivariate analysis by Hispanic/Latino background group showed that Hispanics of Dominican and Puerto Rican backgrounds were at a 3- to 6-fold higher risk of AF than their Mexican counterparts. CONCLUSION: In a diverse representative population of Hispanics/Latinos, overall AF prevalence was low and varied significantly across Hispanic/Latino background groups independent of clinical or demographic factors.


Subject(s)
Atrial Fibrillation/ethnology , Hispanic or Latino , Public Health , Risk Assessment/methods , Adolescent , Adult , Aged , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prevalence , Prospective Studies , Risk Factors , United States/epidemiology , Young Adult
9.
JAMA Intern Med ; 176(2): 219-27, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26785103

ABSTRACT

IMPORTANCE: Bradycardia has been associated with lower cardiovascular disease (CVD) risk in selected populations. There is a paucity of information available about heart rate (HR) less than 50 beats per minute (bpm) among middle-aged or older adults. OBJECTIVE: To determine whether asymptomatic bradycardia was associated with a lower cardiovascular risk profile, less subclinical atherosclerosis, and decreased incident CVD and mortality. DESIGN, SETTING, AND PARTICIPANTS: This retrospective analysis includes 6733 participants of the Multi-Ethnic Study of Atherosclerosis, which recruited men and women free of clinical cardiovascular disease ages 45 to 84 years from 2000 to 2002 and followed them over 10 years for incident CVD events and mortality. The HR was measured by baseline electrocardiogram. The analysis was performed in June 2014. MAIN OUTCOMES AND MEASURES: The association between HR categories with CVD events and all-cause mortality were examined using Cox proportional hazards models adjusted for potential confounders and mediators. RESULTS: The 6733 participants had a mean (SD) age of 62 (10.2) years; 47% were male. The mean (SD) HR was 63 (9.5) bpm among the 5831 participants not taking an HR-modifying drug; 5.3% had an HR lower than 50 bpm. Preliminary results revealed significant interaction for HR categories according to use of HR-modifying drugs for mortality (P = .002); thus, all further analyses were stratified. An HR of less than 50 bpm was not associated with incident CVD in either subgroup (participants taking or not taking HR-modifying drugs). Among participants not taking HR-modifying drugs, the fully adjusted mortality risk was not different for an HR less than 50 bpm (hazard ratio, 0.71 [95% CI, 0.41-1.09]; P = .12) and increased among those with an HR greater than 80 bpm (hazard ratio, 1.49 [95% CI, 1.08-2.05]; P = .01) (reference HR, 60-69 bpm). Among the 902 participants taking HR-modifying drugs there was an elevated mortality risk associated with an HR less than 50 bpm (hazard ratio, 2.42 [95% CI, 1.39-4.20]; P = .002) and with an HR greater than 80 bpm (hazard ratio, 3.55 [95% CI, 1.65-7.65]; P = .001) (reference HR, 60-69 bpm). CONCLUSIONS AND RELEVANCE: In a contemporary, community-based cohort, bradycardia was generally not associated with incident CVD or mortality except for a potential adverse association between bradycardia among those taking HR-modifying drugs.


Subject(s)
Bradycardia/epidemiology , Mortality , Aged , Aged, 80 and over , Asymptomatic Diseases/epidemiology , Atherosclerosis/epidemiology , Ethnicity/statistics & numerical data , Female , Humans , Incidence , Male , Middle Aged , Retrospective Studies , Risk Factors , United States/epidemiology
10.
Am J Cardiol ; 118(12): 1826-1830, 2016 Dec 15.
Article in English | MEDLINE | ID: mdl-27712649

ABSTRACT

The relation between inflammation and prothrombotic state in atrial fibrillation (AF) is well recognized. This suggests a potential role for high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, in improving prediction of stroke in participants with AF. Cox proportional hazard analysis was used to examine the risk of stroke in 25,841 participants (40% black and 55% women) with and without AF who were enrolled in the Reasons for Geographic and Racial Differences in Stroke study from 2003 to 2007. Baseline AF (n = 2,132) was ascertained by electrocardiogram and self-reported history of previous physician diagnosis. Stroke events were identified and adjudicated during 8.3 years of follow-up. A total of 655 incident strokes occurred during follow-up. In a model adjusted for sociodemographics, traditional stroke risk factors, and use of aspirin and warfarin, higher levels of hs-CRP were associated with increased overall stroke risk (hazard ratio [HR] 1.30, 95% confidence interval [CI] 1.10 to 1.54, and HR 1.06, 95% CI 1.01 to 1.12 for hs-CRP >3 mg/L and per 1-SD increase, respectively). Higher levels of hs-CRP continued to be associated with incident stroke in participants without AF (HR 1.31, 95% CI 1.09 to 1.57, and HR 1.06, 95% CI 1.01 to 1.12 for hs-CRP >3 mg/L and per 1-SD increase, respectively) but not in those with AF (HR 1.22, 95% CI 0.78 to 1.91, and HR 1.01, 95% CI 0.82 to 1.23 for hs-CRP >3 mg/L and per 1-SD increase, respectively). In conclusion, although hs-CRP was significantly associated with stroke risk in this population, it seems to be limited to those without AF. These findings suggest a limited value of hs-CRP in improving stroke risk stratification in subjects with AF.


Subject(s)
Atrial Fibrillation/metabolism , C-Reactive Protein/metabolism , Stroke/metabolism , Black or African American , Aged , Animals , Anticoagulants/therapeutic use , Aspirin/therapeutic use , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Case-Control Studies , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Platelet Aggregation Inhibitors/therapeutic use , Prognosis , Proportional Hazards Models , Risk Factors , Stroke/epidemiology , Stroke/etiology , Warfarin/therapeutic use , White People
11.
J Am Coll Cardiol ; 67(2): 139-147, 2016 Jan 19.
Article in English | MEDLINE | ID: mdl-26791059

ABSTRACT

BACKGROUND: The improvement in discrimination gained by adding nontraditional cardiovascular risk markers cited in the 2013 American College of Cardiology/American Heart Association cholesterol guidelines to the atherosclerotic cardiovascular disease (ASCVD) risk estimator (pooled cohort equation [PCE]) is untested. OBJECTIVES: This study assessed the predictive accuracy and improvement in reclassification gained by the addition of the coronary artery calcium (CAC) score, the ankle-brachial index (ABI), high-sensitivity C-reactive protein (hsCRP) levels, and family history (FH) of ASCVD to the PCE in participants of MESA (Multi-Ethnic Study of Atherosclerosis). METHODS: The PCE was calibrated (cPCE) and used for this analysis. The Cox proportional hazards survival model, Harrell's C statistics, and net reclassification improvement analyses were used. ASCVD was defined as myocardial infarction, coronary heart disease-related death, or fatal or nonfatal stroke. RESULTS: Of 6,814 MESA participants not prescribed statins at baseline, 5,185 had complete data and were included in this analysis. Their mean age was 61 years; 53.1% were women, 9.8% had diabetes, and 13.6% were current smokers. After 10 years of follow-up, 320 (6.2%) ASCVD events occurred. CAC score, ABI, and FH were independent predictors of ASCVD events in the multivariable Cox models. CAC score modestly improved the Harrell's C statistic (0.74 vs. 0.76; p = 0.04); ABI, hsCRP levels, and FH produced no improvement in Harrell's C statistic when added to the cPCE. CONCLUSIONS: CAC score, ABI, and FH were independent predictors of ASCVD events. CAC score modestly improved the discriminative ability of the cPCE compared with other nontraditional risk markers.


Subject(s)
Ankle Brachial Index/statistics & numerical data , C-Reactive Protein/analysis , Cholesterol/analysis , Coronary Artery Disease , Coronary Vessels , Family Health , Aged , Aged, 80 and over , Biomarkers/analysis , Coronary Artery Disease/diagnosis , Coronary Artery Disease/drug therapy , Coronary Artery Disease/epidemiology , Coronary Vessels/metabolism , Coronary Vessels/pathology , Disease Progression , Ethnicity/statistics & numerical data , Family Health/ethnology , Family Health/statistics & numerical data , Female , Follow-Up Studies , Health Status Indicators , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Male , Middle Aged , Predictive Value of Tests , Proportional Hazards Models , Risk Assessment/methods , Risk Factors , United States/epidemiology , Vascular Calcification/epidemiology
12.
Cell Commun Adhes ; 10(4-6): 187-91, 2003.
Article in English | MEDLINE | ID: mdl-14681014

ABSTRACT

We previously used electron cryo-crystallography to determine the three-dimensional structure of recombinant gap junction channels formed by a C-terminal truncation mutant of Cx43 (11). The dodecameric channel is formed by the end-to-end docking of two hexameric connexons, each comprised of 24 transmembrane alpha-helices. We have now generated two-dimensional crystals of the recombinant, full-length channel, as well as crystals in which the C-tail has been completely removed by trypsin digestion. Projection density maps at 7.5 A resolution closely resemble our previous analysis of the C-terminal truncation mutant (9). A difference map between the full length and trypsin-treated channels suggests that there are small but significant shifts in protein density upon removal of the C-tail.


Subject(s)
Connexin 43/chemistry , Cryoelectron Microscopy/methods , Gap Junctions/chemistry , Animals , Crystallization , Protein Structure, Tertiary , Recombinant Proteins/chemistry
13.
Am J Cardiol ; 114(11): 1707-12, 2014 Dec 01.
Article in English | MEDLINE | ID: mdl-25282316

ABSTRACT

Calcified coronary arteries are associated with the development of cardiovascular disease and stroke. It is currently unknown whether coronary artery calcium (CAC) is associated with an increased risk for atrial fibrillation (AF). The aim of this study was to address this question in 6,641 participants (mean age 62 ± 10 years, 53% women, 62% nonwhites) from the Multi-Ethnic Study of Atherosclerosis (MESA) who were free of baseline clinical cardiovascular disease and AF. CAC measurements were assessed by cardiac computed tomography at study baseline. AF was ascertained by review of hospital discharge records and from Medicare claims data until December 31, 2010. Cox regression was used to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between CAC and AF. During a median follow-up period of 8.5 years, 308 participants (4.6%) developed AF. In a model adjusted for sociodemographics, cardiovascular risk factors, and potential confounders, higher CAC scores were associated with increased risk for AF (CAC = 0: HR 1.0, referent; CAC = 1 to 100: HR 1.4, 95% CI 1.01 to 2.0; CAC = 101 to 300: HR 1.6, 95% CI 1.1 to 2.4; CAC >300: HR 2.1, 95% CI 1.4 to 2.9). The addition of CAC to the Framingham Heart Study and Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) AF risk scores yielded integrated discrimination improvement of 0.0033 (95% CI 0.0015 to 0.0066) and 0.0028 (95% CI 0.0012 to 0.0057), with relative integrated discrimination improvement of 0.10 (95% CI 0.061 to 0.15) and 0.077 (95% CI 0.040 to 0.11), respectively. In conclusion, CAC is independently associated with increased risk for AF.


Subject(s)
Atrial Fibrillation/epidemiology , Coronary Artery Disease/epidemiology , Coronary Vessels/diagnostic imaging , Vascular Calcification/epidemiology , Black or African American/statistics & numerical data , Aged , Asian/statistics & numerical data , Atrial Fibrillation/ethnology , Cardiac-Gated Imaging Techniques , Coronary Artery Disease/diagnostic imaging , Coronary Artery Disease/ethnology , Female , Follow-Up Studies , Hispanic or Latino/statistics & numerical data , Humans , Male , Middle Aged , Multidetector Computed Tomography , Proportional Hazards Models , Risk Factors , Tomography, X-Ray Computed , United States/epidemiology , Vascular Calcification/diagnostic imaging , Vascular Calcification/ethnology , White People/statistics & numerical data
14.
JAMA Intern Med ; 174(1): 107-14, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24190540

ABSTRACT

IMPORTANCE: Myocardial infarction (MI) is an established risk factor for atrial fibrillation (AF). However, the extent to which AF is a risk factor for MI has not been investigated. OBJECTIVE: To examine the risk of incident MI associated with AF. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort of 23,928 participants residing in the continental United States and without coronary heart disease at baseline were enrolled from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) cohort between 2003 and 2007, with follow-up through December 2009. MAIN OUTCOMES AND MEASURES: Expert-adjudicated total MI events (fatal and nonfatal). RESULTS: Over 6.9 years of follow-up (median 4.5 years), 648 incident MI events occurred. In a sociodemographic-adjusted model, AF was associated with about 2-fold increased risk of MI (hazard ratio [HR], 1.96 [95% CI, 1.52-2.52]). This association remained significant (HR, 1.70 [95% CI, 1.26-2.30]) after further adjustment for total cholesterol, high-density lipoprotein cholesterol, smoking status, systolic blood pressure, blood pressure-lowering drugs, body mass index, diabetes, warfarin use, aspirin use, statin use, history of stroke and vascular disease, estimated glomerular filtration rate, albumin to creatinine ratio, and C-reactive protein level. In subgroup analysis, the risk of MI associated with AF was significantly higher in women (HR, 2.16 [95% CI, 1.41-3.31]) than in men (HR, 1.39 [95% CI, 0.91-2.10]) and in blacks (HR, 2.53 [95% CI, 1.67-3.86]) than in whites (HR, 1.26 [95% CI, 0.83-1.93]); for interactions, P = .03 and P = .02, respectively. On the other hand, there were no significant differences in the risk of MI associated with AF in older (≥75 years) vs younger (<75 years) participants (HR, 2.00 [95% CI, 1.16-3.35] and HR, 1.60 [95% CI, 1.11-2.30], respectively); for interaction, P = .44. CONCLUSIONS AND RELEVANCE: AF is independently associated with an increased risk of incident MI, especially in women and blacks. These findings add to the growing concerns of the seriousness of AF as a public health burden: in addition to being a well-known risk factor for stroke, AF is also associated with increased risk of MI.


Subject(s)
Atrial Fibrillation/epidemiology , Myocardial Infarction/epidemiology , Black or African American/statistics & numerical data , Aged , Atrial Fibrillation/ethnology , Cohort Studies , Diabetes Mellitus/epidemiology , Female , Follow-Up Studies , Humans , Hypertension/epidemiology , Male , Middle Aged , Myocardial Infarction/ethnology , Proportional Hazards Models , Prospective Studies , Renal Insufficiency, Chronic/epidemiology , Risk Factors , Sex Factors , United States/epidemiology , White People/statistics & numerical data
16.
Am J Med ; 126(5): 450.e9-450.e16, 2013 May.
Article in English | MEDLINE | ID: mdl-23582938

ABSTRACT

BACKGROUND: The significance of minor isolated Q waves in the resting electrocardiograms (ECGs) of apparently healthy individuals is unknown. OBJECTIVE: To examine the association between minor isolated Q waves and incident cardiovascular disease events in the Multi-Ethnic Study of Atherosclerosis (MESA). DESIGN: This analysis included 6551 MESA participants (38% white, 28% black, 22% Hispanic, 12% Chinese) who were free of cardiovascular disease at enrollment. Cox proportional hazards models were used to examine the association between minor isolated Q waves defined by the Minnesota ECG Classification with adjudicated incident cardiovascular events. RESULTS: During up to 7.8 years of follow-up, 423 events occurred, with a rate of 10.7 events per 1000 person-years. A significant interaction between minor isolated Q waves and race/ethnicity was observed (P=.030). In models stratified by race/ethnicity and adjusted for demographics, socioeconomic status, common cardiovascular risk factors, and other ECG abnormalities, presence of isolated minor Q waves was significantly associated with incident cardiovascular events in Hispanics (hazard ratio [HR] 2.62; 95% confidence interval [CI], 1.42-4.82), but not in whites (HR 0.65; 95% CI, 0.32-1.33) or blacks (HR 1.46; 95% CI, 0.74-2.89). Despite the statistically significant association in the Chinese population, the small number of events precluded solid conclusions in this race/ethnicity. CONCLUSION: The prognostic significance of minor isolated Q waves varies across races/ethnicities; they carry a high risk for future cardiovascular events in apparently healthy Hispanics, but not in whites or blacks.


Subject(s)
Atherosclerosis/ethnology , Cardiovascular Diseases/epidemiology , Aged , Aged, 80 and over , Cardiovascular Diseases/ethnology , Electrocardiography , Ethnicity , Female , Follow-Up Studies , Humans , Incidence , Male , Middle Aged , Proportional Hazards Models , Prospective Studies , Risk Factors
17.
Am J Cardiol ; 111(1): 118-24, 2013 Jan 01.
Article in English | MEDLINE | ID: mdl-23062314

ABSTRACT

Widening of the electrocardiographic (ECG) spatial QRS-T angle has been predictive of cardiovascular disease (CVD) events in the general population. However, its prognostic significance in human immunodeficiency virus (HIV)-infected patients remains unknown. The spatial QRS-T angle was derived from the baseline resting 12-lead electrocardiogram of 4,453 HIV-infected patients aged 43.5 ± 9.3 years from the Strategies for Management of Antiretroviral Therapy (SMART) trial. CVD events were identified during a median follow-up of 28.7 months. Quartiles of the spatial QRS-T angle was calculated for men and women separately, and values in the upper quartile were considered as a widened angle (values >74° for women and >93° for men). A multivariate Cox proportional hazards analysis was used to examine the association between a widened baseline spatial QRS-T angle and incident CVD events. During 11,965 person-years of follow-up, 152 CVD events occurred at a rate of 1.27 events/100 person-years. The rate of CVD events in those with a widened spatial QRS-T angle was almost double the rate in those with a normal spatial QRS-T angle (rate ratio 1.94, 95% confidence interval 1.40 to 2.69; p <0.001). In a model adjusted for study treatment arm, demographics, CVD risk factors, HIV characteristics, inflammatory markers, and other ECG abnormalities, a widened spatial QRS-T angle was associated with a >50% increased risk of CVD events compared to a normal spatial QRS-T angle (hazard ratio 1.53, 95% confidence interval 1.07 to 2.17; p = 0.02). No interaction was seen by SMART trial arm (p value for interaction = 0.37) or gender (p value for interaction = 0.84). In conclusion, a widened spatial QRS-T angle was independently predictive of CVD events in HIV-infected patients receiving antiretroviral therapy. This highlights the potential role of routine electrocardiography as a simple noninvasive CVD risk-screening tool in HIV-infected patients.


Subject(s)
Anti-Retroviral Agents/therapeutic use , Arrhythmias, Cardiac/epidemiology , Electrocardiography , HIV Infections/complications , HIV , Adolescent , Adult , Arrhythmias, Cardiac/etiology , Arrhythmias, Cardiac/physiopathology , Female , Follow-Up Studies , Global Health , HIV Infections/drug therapy , HIV Infections/physiopathology , Humans , Incidence , Male , Prognosis , Proportional Hazards Models , Prospective Studies , Risk Factors , Survival Rate/trends , Young Adult
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