Studies have linked elevated total homocysteine (tHcy) levels to atherosclerotic carotid plaque development, but data are limited to predominantly white populations. We examined the association ...between tHcy and carotid plaque burden and morphology in a multiethnic cohort.
In the Northern Manhattan Study, we conducted a cross-sectional analysis among 1327 stroke-free subjects (mean age, 66 ± 9; 41% men; 19% black; 62% Hispanic; 17% white) with serum tHcy and ultrasonographic assessment of plaque morphology measured by gray-scale median (GSM) and total plaque area (TPA). GSM and TPA were examined in 4 categories. High and low GSM categories were considered echodense and echolucent plaque, respectively, and compared with no plaque. Logistic regression models were used to assess the associations of tHcy with GSM and TPA adjusting for demographics, vascular risk factors, renal insufficiency, and B(12) deficiency.
The mean tHcy was 9.4 ± 4.8 µmol/L (median=8.6). The prevalence of carotid plaque was 57% (52% among Hispanics, 58% black, and 70% white). Among those with plaque, the mean TPA was 20.3 ± 20.6 mm(2) (median=13.6) and mean GSM 90.9 ± 28.5 (median=93.0). The top 2 tHcy quartiles (versus quartile 1) had an elevated risk of having either echolucent plaque (tHcy Q3, odds ratio OR=1.8; 95% confidence interval {CI} 1.2-2.8; tHcy Q4, OR=1.9 95% CI 1.2-3.1) or echodense plaque (tHcy Q3, OR=1.7 95% CI, 1.1-2.7; tHcy Q4, OR=1.9 95% CI, 1.2-3.2). The top 2 tHcy quartiles were also more likely to be in the highest TPA category (tHcy Q3, OR=1.8 95% CI, 1.1-3.0; tHcy Q4, OR=2.2 95% CI, 1.3-3.7).
In this population-based multiethnic cohort, elevated tHcy was independently associated with plaque morphology and increased plaque area, subclinical markers of stroke risk.
Coronary collateral circulation protects cardiac tissues from myocardial infarction damage and decreases sudden cardiac death. So far, it is unclear how coronary collateralization varies by ...race-ethnicity groups and by sex.
We assessed 868 patients with obstructive CAD. Patients were assessed for collateral grades based on Rentrop grading system, as well as other covariates. DNA samples were genotyped using the Affymetrix 6.0 genotyping array. To evaluate genetic contributions to collaterals, we performed admixture mapping using logistic regression with estimated local and global ancestry.
Overall, 53% of participants had collaterals. We found difference between sex and racial-ethnic groups. Men had higher rates of collaterals than women (P-value = 0.000175). White Hispanics/Latinos showed overall higher rates of collaterals than African Americans and non-Hispanic Whites (59%, 50% and 48%, respectively, P-value = 0.017), and especially higher rates in grade 1 and grade 3 collateralization than the other two populations (P-value = 0.0257). Admixture mapping showed Native American ancestry was associated with the presence of collaterals at a region on chromosome 17 (chr17:35,243,142-41,251,931, β = 0.55, P-value = 0.000127). African ancestry also showed association with collaterals at a different region on chromosome 17 (chr17: 32,266,966-34,463,323, β = 0.38, P-value = 0.00072).
In our study, collateralization showed sex and racial-ethnic differences in obstructive CAD patients. We identified two regions on chromosome 17 that were likely to harbor genetic variations that influenced collateralization.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background Premature ventricular contractions (PVCs) and nonsustained ventricular tachycardia (NSVT) are known to be associated with reduced left ventricular (LV) ejection fraction and adverse ...outcomes in patients with structural heart disease. The relationship between subclinical LV dysfunction and ventricular arrhythmias in the general population is not established. Methods and Results Participants in the SAFARIS (Subclinical Atrial Fibrillation and Risk of Ischemic Stroke) study with normal left ventricular ejection fraction (n=503; mean age 77 years, 63% women) underwent 14-day electrocardiographic monitoring and 2-dimensional echocardiography. Frequent PVCs were defined as PVCs >500 per 24 hours and NSVT as ≥4 consecutive ventricular ectopic beats. Reduced LV global longitudinal strain (GLS) was used as an indicator of subclinical LV dysfunction. Seventy-six participants (15.1%) had PVCs >500/d, 117 (23.3%) had NSVT episodes. LV GLS was significantly reduced in both frequent PVCs and NSVT groups (
<0.01). In multivariable analyses, lower LV GLS was associated with frequent PVCs (adjusted odds ratio aOR, 1.19 95% CI, 1.09-1.30 per unit reduction;
<0.001) and NSVT (aOR, 1.09 95% CI, 1.01-1.17;
=0.036) independently of established risk factors and other echocardiographic parameters. Abnormal LV GLS (>-15.8%) carried a 2-fold increase in risk of ventricular arrhythmias (aOR, 2.18,
=0.029 for PVCs; aOR, 2.09,
=0.026 for NSVT). Conclusions PVCs and NSVT episodes were frequent in this community-based elderly cohort with normal left ventricular ejection fraction and were independently associated with lower LV GLS. The association between LV dysfunction and ventricular arrhythmias is present at an early, subclinical stage, an observation that carries possible preventative implications.
Abstract Objective Periodontal infections have been linked to cardiovascular disease, including atherosclerosis, and systemic inflammation has been proposed as a possible mediator. Secretory ...phospholipase A2 (s-PLA2) and Lipoprotein-associated PLA2 (Lp-PLA2) are inflammatory enzymes associated with atherosclerosis. No data are available on the association between oral microbiota and PLA2s. We studied whether a relationship exists between periodontal microbiota and the activities of these enzymes. Methods The Oral Infection and Vascular Disease Epidemiology Study (INVEST) collected subgingival biofilms and serum samples from 593 dentate men and women (age 68.7 ± 8.6 years). 4561 biofilm samples were collected in the two most posterior teeth of each quadrant (average 7/participant) for quantitative assessment of 11 bacterial species using DNA–DNA checkerboard hybridization. Mean concentration of s-PLA2 and activities of s-PLA2 and Lp-PLA2 were regressed on tertiles of etiologic dominance (ED). ED is defined as the level of presumed periodontopathic species/combined level of all eleven species measured, and represents the relative abundance of periodontopathic organisms. Analyses were adjusted for age, sex, race/ethnicity, education, smoking, BMI, diabetes, LDL cholesterol and HDL cholesterol, and systolic blood pressure. Results Higher levels of s-PLA2 activity were observed across increasing tertiles of etiologic dominance (0.66 ± 0.04 nmol ml−1 min−1 , 0.73 ± 0.04 nmol ml−1 min−1 , 0.89 ± 0.04 nmol ml−1 min−1; p < 0.001), with also a trend of association between Lp-PLA2 activity and ED (p = 0.07), while s-PLA2 concentration was unrelated to ED. Conclusion Increasingly greater s-PLA2 activity at higher tertiles of etiologic dominance may provide a mechanistic explanatory link of the relationship between periodontal microbiota and vascular diseases. Additional studies investigating the role of s-PLA2 are needed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPUK
OBJECTIVES/GOALS: The goal of this study is to highlight the unique characteristics of Miami CTSIs Master of Science in Clinical and Translational Investigation (MSCTI) as part of CTSIs overall ...translational workforce development program and to describe program outcomes. METHODS/STUDY POPULATION: The MSCTI at the University of Miami offers a structured, individualized, and mentored educational program that trains students in the principles and practice of translational science and clinical research. Based on student feedback and needs assessment, three courses were specifically created for the program to include additional scientific cognates and promote essential skills for the translational research workforce – team science and entrepreneurship, research ethics, and writing for clinical and translational science. A fourth course on applied statistics is currently under development that provides training in practical statistical knowledge required for clinician-researchers. Career trajectory of graduates and academic output were tracked through surveys and secondary data collection. RESULTS/ANTICIPATED RESULTS: The MSCTI Program has enrolled 76 students over its lifetime, including KL2 scholars, NIH K scholars and T32 trainees; with 25% of students holding foreign degrees. In addition to traditional outcomes such as funding and publications, qualitative case studies will highlight scientific impact and career progress of students. The program has performed exceptionally well in recruiting underrepresented persons in research, with 41% of the students identifying as Hispanic, and 52% of the students as female. Of the graduates, 84% have gone on to achieve leadership positions in NIH and pursue research careers in academic institutions, while 16% have moved to industry, government, or non-profit careers. Overall, 92% of graduates were engaged in research after two years of graduating from the program. DISCUSSION/SIGNIFICANCE: Miami CTSIs MSCTI Program has trained students with a wide range of incoming experience to establish successful careers in clinical and translational research and is a critical component of CTSIs translational workforce development program.
Abstract
Aims
Heart disease is associated with an increased risk for ischaemic stroke. However, the predictive value of reduced left ventricular ejection fraction (LVEF) for stroke is controversial ...and only observed in patients with severe reduction. LV global longitudinal strain (LV GLS) can detect subclinical LV systolic impairment when LVEF is normal. We investigated the prognostic role of LV GLS for incident stroke in a predominantly elderly cohort.
Methods and results
Two-dimensional echocardiography with speckle tracking was performed in the Cardiac Abnormalities and Brain Lesions (CABL) study. Among 708 stroke-free participants (mean age 71.4 ± 9.4 years, 60.9% women), abnormal LV GLS (>−14.7%: 95% percentile of the subgroup without risk factors) was detected in 133 (18.8%). During a mean follow-up of 10.8 ± 3.9 years, 47 participants (6.6%) experienced an ischaemic stroke (26 cardioembolic or cryptogenic, 21 other subtypes). The cumulative incidence of ischaemic stroke was significantly higher in participants with abnormal LV GLS than with normal LV GLS (P < 0.001). In multivariate stepwise logistic regression analysis, abnormal LV GLS was associated with ischaemic stroke independently of cardiovascular risk factors including LVEF, LV mass, left atrial volume, subclinical cerebrovascular disease at baseline, and incident atrial fibrillation hazard ratio (HR): 2.69, 95% confidence interval (CI): 1.47–4.92; P = 0.001. Abnormal LV GLS independently predicted cardioembolic or cryptogenic stroke (adjusted HR: 3.57, 95% CI: 1.51–8.43; P = 0.004) but not other subtypes.
Conclusion
LV GLS was a strong independent predictor of ischaemic stroke in a predominantly elderly stroke-free cohort. Our findings provide insights into the brain–heart interaction and may help improve stroke primary prevention strategies.
Graphical Abstract
Graphical Abstract
Background
No prospective studies exist on the relationship between change in periodontal clinical and microbiological status and progression of carotid atherosclerosis.
Methods and Results
The Oral ...Infections and Vascular Disease Epidemiology Study examined 420 participants at baseline (68±8 years old) and follow‐up. Over a 3‐year median follow‐up time, clinical probing depth (PD) measurements were made at 75 766 periodontal sites, and 5008 subgingival samples were collected from dentate participants (average of 7 samples/subject per visit over 2 visits) and quantitatively assessed for 11 known periodontal bacterial species by DNA‐DNA checkerboard hybridization. Common carotid artery intima‐medial thickness (CCA‐IMT) was measured using high‐resolution ultrasound. In 2 separate analyses, change in periodontal status (follow‐up to baseline), defined as (1) longitudinal change in the extent of sites with a ≥3‐mm probing depth (Δ%PD≥3) and (2) longitudinal change in the relative predominance of bacteria causative of periodontal disease over other bacteria in the subgingival plaque (Δetiologic dominance), was regressed on longitudinal CCA‐IMT progression adjusting for age, sex, race/ethnicity, diabetes, smoking status, education, body mass index, systolic blood pressure, and low‐density lipoprotein cholesterol and high‐density lipoprotein cholesterol. Mean (SE) CCA‐IMT increased during follow‐up by 0.139±0.008 mm. Longitudinal IMT progression attenuated with improvement in clinical or microbial periodontal status. Mean CCA‐IMT progression varied inversely across quartiles of longitudinal improvement in clinical periodontal status (Δ%PD≥3) by 0.18 (0.02), 0.16 (0.01), 0.14 (0.01), and 0.07 (0.01) mm (P for trend<0.0001). Likewise, mean CCA‐IMT increased by 0.20 (0.02), 0.18 (0.02), 0.15 (0.02), and 0.12 (0.02) mm (P<0.0001) across quartiles of longitudinal improvement in periodontal microbial status (Δetiologic dominance).
Conclusion
Longitudinal improvement in clinical and microbial periodontal status is related to a decreased rate of carotid artery IMT progression at 3‐year average follow‐up.
Prediction of decline to dementia using objective biomarkers in high-risk patients with amnestic mild cognitive impairment (aMCI) has immense utility. Our objective was to use multimodal MRI to (1) ...determine whether accurate and precise prediction of dementia conversion could be achieved using baseline data alone, and (2) generate a map of the brain regions implicated in longitudinal decline to dementia.
Participants meeting criteria for aMCI at baseline (
= 55) were classified at follow-up as remaining stable/improved in their diagnosis (
= 41) or declined to dementia (
= 14). Baseline T1 structural MRI and resting-state fMRI (rsfMRI) were combined and a semi-supervised support vector machine (SVM) which separated stable participants from those who decline at follow-up with maximal margin. Cross-validated model performance metrics and MRI feature weights were calculated to include the strength of each brain voxel in its ability to distinguish the two groups.
Total model accuracy for predicting diagnostic change at follow-up was 92.7% using baseline T1 imaging alone, 83.5% using rsfMRI alone, and 94.5% when combining T1 and rsfMRI modalities. Feature weights that survived the
< 0.01 threshold for separation of the two groups revealed the strongest margin in the combined structural and functional regions underlying the medial temporal lobes in the limbic system.
An MRI-driven SVM model demonstrates accurate and precise prediction of later dementia conversion in aMCI patients. The multi-modal regions driving this prediction were the strongest in the medial temporal regions of the limbic system, consistent with literature on the progression of Alzheimer's disease.
Life's Essential 8 (LE8) is a new metric to define cardiovascular health. We aimed to describe LE8 among Hispanics/Latinos and its association with incident hypertension.
The HCHS/SOL (Hispanic ...Community Health Study/Study of Latinos) is a study of Hispanic/Latino adults aged 18 to 74 years from 4 US communities. At visit 1 (2008-2011), information on behavioral and clinical factors (diet, smoking status, physical activity, sleep duration, body mass index, blood pressure, cholesterol, fasting glucose, and medication use) were measured and used to estimate an LE8 score (range, 0-100) for 14 772 participants. Hypertension was defined as systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg, or self-reported use of antihypertensive medications. Among the 5667 participants free from hypertension at visit 1, we used Poisson regression models to determine the multivariable adjusted association between LE8 and incident hypertension in 2014 to 2017. All analyses accounted for the complex survey design of the study. Mean population age was 41 years, and 21.6% (SE, 0.7) had high cardiovascular health (LE8 ≥80). Mean LE8 score (68.2; SE, 0.3) varied by Hispanic/Latino background (
<0.05), ranging from 72.6 (SE, 0.3) among Mexican Americans to 62.2 (SE, 0.4) among Puerto Ricans. Each 10-unit decrement in LE8 score was associated with a 22% increased risk of hypertension over ≈6 years (incident density ratio, 1.22 95% CI, 1.16-1.29).
Only 1 in 5 Hispanic/Latino adults had high cardiovascular health, and LE8 varied substantially across Hispanic/Latino background groups. Improvements in other components of cardiovascular health may result in a lower risk of developing hypertension.
Background Less than 40% of acute stroke patients have computed tomography (CT) imaging performed within 25 minutes of hospital arrival. We aimed to examine the race-ethnic and sex differences in ...door-to-CT (DTCT) ≤25 minutes in the FSR (Florida Stroke Registry). Methods and Results Data were collected from 2010 to 2018 for 63 265 patients with acute ischemic stroke from the FSR and secondary analysis was performed on 15 877 patients with intravenous tissue plasminogen activator-treated ischemic stroke. Generalized estimating equation models were used to determine predictors of DTCT ≤25. DTCT ≤25 was achieved in 56% of cases of suspected acute stroke, improving from 36% in 2010 to 72% in 2018. Women (odds ratio OR, 0.90; 95% CI, 0.87-0.93) and Black (OR, 0.88; CI, 0.84-0.94) patients who had strokes were less likely, and Hispanic patients more likely (OR, 1.07; CI, 1.01-1.14), to achieve DTCT ≤25. In a secondary analysis among intravenous tissue plasminogen activator-treated patients, 81% of patients achieved DTCT ≤25. In this subgroup, women were less likely to receive DTCT ≤25 (0.85, 0.77-0.94) whereas no significant differences were observed by race or ethnicity. Conclusions In the FSR, there was considerable improvement in acute stroke care metric DTCT ≤25 in 2018 in comparison to 2010. However, sex and race-ethnic disparities persist and require further efforts to improve performance and reduce these disparities.
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