Post-Traumatic Stress Disorder and Cardiovascular Diseases: A Cohort Study of Men and Women Involved in Cleaning the Debris of the World Trade Center Complex

BACKGROUND: To determine whether post-traumatic stress disorder (PTSD) is a risk factor for myocardial infarction (MI) and stroke, beyond the expected effects from recognized cardiovascular risk factors and depression. METHODS AND RESULTS: World Trade Center-Heart is an observational prospective cohort study of 6481 blue-collar first responders nested within the World Trade Center Health Program in New York City. Baseline measures in 2012 and 2013 included blood pressure, weight and height, and blood lipids. PTSD, depression, smoking, and dust exposure during the 2001 cleanup were self-reported. During the 4-year follow-up, outcomes were assessed through (1) interview-based incident, nonfatal MI, and stroke, validated in medical charts (n=118); and (2) hospitalizations for MI and stroke for New York city and state residents (n=180). Prevalence of PTSD was 19.9% in men and 25.9% in women, that is, at least twice that of the general population. Cumulative incidence of MI or stroke was consistently larger for men or women with PTSD across follow-up. Adjusted hazard ratios (HRs) were 2.22 (95% confidence interval [CI], 1.30–3.82) for MI and 2.51 (95% CI, 1.39–4.57) for stroke. For pooled MI and stroke, adjusted HRs were 2.35 (95% CI, 1.57–3.52) in all and 1.88 (95% CI, 1.01–3.49) in men free of depression. Using hospitalization registry data, adjusted HRs were 2.17 (95% CI, 1.41–3.32) for MI; 3.01 (95% CI, 1.84–4.93) for stroke; and for pooled MI and stroke, the adjusted HR was 2.40 (95% CI, 1.73–3.34) in all, HR was 2.44 (95% CI, 1.05–5.55) in women, and adjusted HR was 2.27 (95% CI, 1.41–3.67) in men free of depression. World Trade Center dust exposure had no effect. CONCLUSIONS: This cohort study confirms that PTSD is a risk factor for MI and stroke of similar magnitude in men and women, independent of depression

Cigarette Smoking and Carotid Plaque Echodensity in the Northern Manhattan Study

BACKGROUND: We sought to determine the association between cigarette smoking and carotid plaque ultrasound morphology in a multi-ethnic cohort. METHODS: We analyzed 1,743 stroke-free participants (mean age, 65.5±8.9 years; 60% women; 18% white, 63% Hispanic, 19% black; 14% current and 38% former smokers, 48% never smoked) from the Northern Manhattan Study using an ultrasound index of plaque echodensity, the Gray-Scale Median (GSM). Echolucent plaque (low GSM) represents soft plaque and echodense (high GSM) more calcified plaque. The mean GSM weighted by plaque area for each plaque was calculated for those with multiple plaques. Quintiles of GSM were compared to no plaque. Multinomial logistic regression models were used to assess associations of cigarette smoking with GSM, adjusting for demographics and vascular risk factors. RESULTS: Among subjects with carotid plaque (58%), the mean GSM scores for quintiles 1 to 5 were 48, 72, 90, 105, and 128, respectively. Current smokers had over a 2-fold increased risk of having GSM in quintile 1 (Odds Ratio [OR]=2.17; 95% Confidence Interval [CI], 1.34–3.52), quintile 2 (OR=2.33; CI, 1.42–3.83), quintile 4 (OR=2.05; CI, 1.19–3.51), and quintile 5 (OR=2.13; CI, 1.27–3.56) but not in quintile 3 (OR=1.18; CI, 0.67–2.10) as compared to never smokers in fully adjusted models. Former smokers had increased risk in quintile 2 (OR=1.46; CI, 1.00–2.12), quintile 3 (OR=1.56; CI, 1.09–2.24), quintile 4 (OR=1.66; CI, 1.13–2.42), and quintile 5 (OR=1.73; CI, 1.19–2.51), but not in quintile 1 (OR=1.05; CI, 0.72–1.55). CONCLUSIONS: A non-linear, Vshaped like relationship between current cigarette smoking and plaque echodensity was observed. Former smokers were at highest risk for plaques in high GSM quintiles. Thus, current smokers were more likely to have either soft or calcified plaques and former smokers were at greater risk of only echodense plaques when compared against never smokers. Further research is needed to determine if plaque morphology mediates an association between smoking and clinical vascular events

Abstract 90: Race, Ethnic, and Sex Disparities in Stroke Incidence in the Northern Manhattan Study

Background: An excess incidence of strokes among blacks vs whites has been shown previously, but data on disparities related to Hispanic ethnicity remains limited. This study examines race, ethnic, and sex differences in stroke incidence in the multi-ethnic, yet largely Caribbean Hispanic, Northern Manhattan Study (NOMAS). Methods: The study population included participants in the prospective population-based NOMAS, followed for a mean of 13±7 years. Cox proportional hazards models were constructed to estimate the hazard ratios and 95% confidence intervals (HR, 95%CI) for the association between race/ethnicity and sex with confirmed incident stroke of any subtype and ischemic stroke, stratified by age and adjusting for sociodemographics and vascular risk factors. Results: Among 3,298 participants (mean baseline age 69±10, 37% men, 24% black, 21% white, 52% Hispanic), 477 incident strokes accrued (394 ischemic, 43 ICH, 9 SAH). The most common ischemic subtype was cardioembolic, followed by lacunar infarcts, then cryptogenic. The greatest incidence rate was observed in blacks (13/1000 person-years [PY]), followed by Hispanics (11/1000 PY), and lowest in whites (8/1000 PY), and this order was observed for crude incidence rates until age 75. By age 85 the greatest incidence rate was in Hispanics. Blacks had an increased stroke risk vs whites overall in fully adjusted models (HR=1.37, 95% CI=1.02-1.84), and stratified analyses showed that this disparity was driven by women age ≥70 (HR=1.69, 1.05-2.73). The increased rate of stroke observed for Hispanics (age/sex-adjusted HR=1.50, 1.15-1.94) was largely explained by education and insurance status (a proxy for socieoeconomic status; HR after further adjusting for these variables=1.15, 0.84-1.58), but remained significant for women age ≥70. Men had an increased rate of stroke compared to women (fully adjusted HR=1.48, 1.21-1.81). Conclusions: This study provides novel data regarding the increased stroke risk among Caribbean Hispanics. Results highlight the need to create culturally-tailored campaigns to reach blacks and Hispanic populations to reduce race/ethnic stroke disparities, and support the important role of low socioeconomic status in driving an elevated risk among Caribbean Hispanics

Abstract 2145: The Long-term Trajectory Of Functional Decline Before And After Stroke: The Northern Manhattan Study

Background: Previous research in our population showed a steeper long-term decline in functional status after first ischemic stroke among those with Medicaid or no insurance compared to those with Medicare or private insurance. With only post-stroke data, it was unknown whether these findings were caused by the stroke. We sought to compare the long-term trajectory of functional status before and after ischemic stroke. Methods: The Northern Manhattan Study contains a prospective, population-based study of stroke-free individuals >40 years of age, followed for a median of 10 years. The Barthel index (BI) was assessed annually. Generalized estimating equations were used to assess functional decline over time before and after stroke. The 6 months after stroke were ignored, since the course of recovery during this period is well documented, and our interest was the long-term course of functional status. Follow-up was censored at the time of recurrent stroke. Sociodemographic and medical risk factors were included and results were stratified by insurance status. Linearity of the curves was evaluated by plotting residuals against time and with a lowess curve. Results: Among 3298 participants, 261 had an ischemic stroke during follow-up, of which 51 died within 6 months of stroke. Among the remaining 210 participants, mean age at stroke (standard deviation) was 77+9 years, 38% were male, 52% were Hispanic, 37% had diabetes, and 31% had coronary artery disease. There was no difference in functional decline over time before and after stroke (p= 0.51), with a decline of 0.96 BI points per year before stroke (p<.0001) and 1.24 after stroke (p=0.001). However, when stratified by insurance status, among those with Medicaid or no insurance, in a fully adjusted model, there was a difference in slope before and after stroke (p=0.04), with a decline of 0.58 BI points per year before stroke (p=0.02) and 1.94 after stroke (p=0.001). Other predictors of worse functional status were increasing age, female sex, diabetes, and being married. Conclusion: In this large, prospective, population-based study with long-term follow-up, there was a significantly steeper decline in functional status after ischemic stroke compared to before stroke among those with Medicaid or no insurance, after adjusting for confounders. The cause of this differential decline is not known but may be related to poor control of risk factors, silent strokes, or an effect of socioeconomic status

Abstract W MP65: Moderate to Severe Left Atrial Enlargement is Associated with Cardioembolic or Cryptogenic Stroke Recurrence in a Multiethnic Cohort: The Northern Manhattan Study

Background: While left atrial (LA) enlargement increases incident stroke risk, the association with recurrent stroke is unclear. Our aim was to determine the association of LA enlargement (LAE) with stroke recurrence risk and recurrent stroke subtypes likely related to embolism (cryptogenic or cardioembolic). Methods: We enrolled 655 first ischemic stroke patients in the Northern Manhattan Stroke Study. LA size was measured by two-dimensional echocardiogram as part of the clinical evaluation and patients were followed annually for up to 5 years. LA size adjusted for sex and body surface area was categorized into three groups: normal (52.7%), mild LAE (31.6%), and moderate to severe LAE (15.7%). The outcomes were total recurrent stroke, and recurrent combined cryptogenic or cardioembolic stroke. Cox proportional hazard models assessed the association between LA size and risk of stroke recurrence. Results: Of 655 patients, LA size data was present in 529 (81%). Mean age was 69 ± 13 years; 46% were male and 18% had atrial fibrillation. Over a median of 4 years, recurrent stroke occurred in 83 patients (16%), 29 were cardioembolic or cryptogenic stroke. After adjusting for baseline demographics and risk factors including atrial fibrillation and congestive heart failure, compared to normal LA size, moderate to severe LAE was associated with greater risk of recurrent combined cardioembolic or cryptogenic stroke (adjusted HR 2. 99, 95% CI 1. 10 to 8.13), but not with risk of total stroke recurrence (adjusted HR 1.18, 95% CI 0.60 to 2.32). Mild LAE was not associated with either total stroke recurrence or the combined recurrent cryptogenic or cardioembolic stroke subtypes. Conclusion: Moderate to severe LAE is an independent marker of recurrent cardioembolic or cryptogenic stroke in a multiethnic cohort of ischemic stroke patients. Future research is needed to determine if anticoagulant use reduces the risk of recurrence in ischemic stroke patients with moderate to severe LAE

Abstract TP176: Carotid Arterial Diameters as an Effect Modifier of Pulsatile Hemodynamics and Brain Perivascular Spaces

Introduction: Brain perivascular spaces (PVS) are associated with higher pulse pressures and may be imaging biomarkers of systemic arterial stiffness. We hypothesized that larger proximal arterial diameters act as effect modifiers between downstream PVS and surrogate measures of arterial stiffness. Methods: Stroke-free Northern Manhattan Study participants with brain MRI and carotid ultrasound were analyzed. Perivascular spaces were rated semi-quantitatively as ≤ 3 mm voids on axial T1 images without associated FLAIR hyperintensities. Intracranial brain arterial diameters were measured on MRA. The right common carotid artery (CCA) was assessed by high resolution B-mode ultrasound to obtain systolic and diastolic diameters. CCA stiffness was calculated as a ratio between log n transformed systolic-diastolic blood pressure and (systolic - diastolic diameter)/diastolic diameter. We created generalized linear models using and pulse pressure (PP) and CCA stiffness as predictors as independent variables and right anterior PVS score as the outcome, adjusting for demographics, risk factors, head size. Results: Among 941 participants (N=941, mean age 71 ± 9 year, 60% women, 66% Hispanic), PP was associated with PVS score (B=0.003, P=0.04) in an adjusted model. There was a statistical interaction between PP, right CCA diastolic diameter, and right intracranial arterial diameters as predictors of right anterior PVS score (P=0.03), but this interaction was not significant for posterior fossa PVS score (B=0.015, P=0.191), or when substituting right intracranial arterial diameters with the basilar artery diameter (B=-0.004, P=0.191). The association between PP (P=0.003) or carotid stiffness (P=0.002) with right anterior PVS score was greater among participants with larger right intracranial arterial and larger CCA diameters. Conclusions: Arterial stiffness is related to downstream PVS in those with larger proximal arterial diameters. These results suggest a mechanical effect of pulsatility on brain parenchyma and further studies are needed to enhance our understanding of the link between systemic hemodynamics and brain diseases such as dementia and stroke

Duration of Diabetes and Risk of Ischemic Stroke

BACKGROUND AND PURPOSE: Diabetes increases stroke risk, but whether diabetes status immediately prior to stroke improves prediction, and whether duration is important, are less clear. We hypothesized that diabetes duration independently predicts ischemic stroke. METHODS: Among 3,298 stroke-free participants in the Northern Manhattan Study (NOMAS), baseline diabetes and age at diagnosis were determined. Incident diabetes was assessed annually (median=9 years). Cox proportional hazard models were used to estimate hazard ratios and 95% confidence intervals (HR, 95% CI) for incident ischemic stroke using baseline diabetes, diabetes as a time-dependent covariate, and duration of diabetes as a time-varying covariate; models were adjusted for demographic and cardiovascular risk factors. RESULTS: Mean age was 69±10 years (52% Hispanic, 21% white, and 24% black); 22% were diabetic at baseline and 10% developed diabetes. There were 244 ischemic strokes, and both baseline diabetes (HR 2.5, 95% CI 1.9-3.3) and diabetes considered as a time-dependent covariate (HR 2.4, 95% CI 1.8-3.2) were similarly associated with stroke risk. Duration of diabetes was associated with ischemic stroke (adjusted HR=1.03 per year with diabetes, 95% CI=1.02-1.04). Compared to non-diabetic participants, those with diabetes for 0-5 years (adjusted HR=1.7, 95% CI=1.1-2.7), 5-10 years (adjusted HR=1.8, 95% CI=1.1-3.0), and ≥10 years (adjusted HR=3.2, 95% CI=2.4-4.5) were at increased risk. CONCLUSION: Duration of diabetes is independently associated with ischemic stroke risk adjusting for risk factors. The risk increases 3% each year, and triples with diabetes ≥10 years

Impacts of cerebral small vessel disease on global and domain‐specific cognition

BackgroundThe 2021 Alzheimer’s Association International Conference press release forecasted global dementia cases to triple by 2050, due to the major contribution of increases in vascular risk factors. The Global Vascular Risk Score (GVRS) was developed to predict vascular events using a point‐based index for risk factor variables, though has demonstrated to be a significant predictor of global and domain‐specific cognitive performance in a multi‐ethnic cohort (Rundek, T. et al. Global Vascular Risk Score and CAIDE Dementia Risk Score Predict Cognitive Function in the Northern Manhattan Study. J Alzheimers Dis 73, 1221‐1231 (2020)). However, more than half of the variance in global and domain‐specific cognitive performance is still unexplained by GVRS variables. We sought to explain additional variance in cognitive performance by addition of MRI biomarkers of cerebral small vessel disease to the GVRS model.MethodWe included 1290 subjects from the multiethnic Northern Manhattan Study population (age 64+/‐8 years, 40% women, 66% Hispanic, 17% non‐Hispanic Black, 15% non‐Hispanic White, education 10+/‐5 years). Multivariate linear regression models were employed to assess the added value of the cerebral small vessel disease MRI measures (white matter hyperintensity volume, silent brain infarcts, cerebral microbleeds, and perivascular spaces) beyond GVRS variables in explaining more variance in global and domain‐specific (episodic memory, executive function, semantic memory, and processing speed) cognitive performance. The explained variance (R2) of the GVRS model was compared to the proposed model with added imaging markers to determine their predictive performance. Statistical significance was determined using F‐statistic difference test between the models.ResultThe explained variance (R2) and F‐statistic for models of global and domain‐specific cognition are in the table. Addition of MRI measures significantly improved the model for global cognition (F(4, 1108) = 2.68, p < 0.05) and domain‐specific cognitive performance models of episodic memory (F(4, 1096) = 3.34, p < 0.01) and processing speed (F(4, 1096) = 2.40, p < 0.05).ConclusionMRI measures of cerebral small vessel disease explain more variance in global cognition, episodic memory, and processing speed than GVRS factors alone. However, most of the variance in cognitive performance remains unexplained

Left atrial enlargement and stroke recurrence: the Northern Manhattan Stroke Study

Although left atrial enlargement (LAE) increases incident stroke risk, the association with recurrent stroke is less clear. Our aim was to determine the association of LAE with recurrent stroke most likely related to embolism (cryptogenic and cardioembolic) and all ischemic stroke recurrences. We followed 655 first ischemic stroke patients in the Northern Manhattan Stroke Study for ≤5 years. LA size from 2D echocardiography was categorized as normal LAE (52.7%), mild LAE (31.6%), and moderate-severe LAE (15.7%). We used Cox proportional hazard models to calculate the hazard ratios and 95% confidence intervals for the association of LA size and LAE with recurrent cryptogenic/cardioembolic and total recurrent ischemic stroke. LA size was available in 529 (81%) patients. Mean age at enrollment was 69±13 years; 45.8% were male, 54.0% Hispanic, and 18.5% had atrial fibrillation. Over a median of 4 years, there were 65 recurrent ischemic strokes (29 were cardioembolic or cryptogenic). In multivariable models adjusted for confounders, including atrial fibrillation and heart failure, moderate-severe LAE compared with normal LA size was associated with greater risk of recurrent cardioembolic/cryptogenic stroke (adjusted hazard ratio 2.83, 95% confidence interval 1.03-7.81), but not total ischemic stroke (adjusted hazard ratio 1.06, 95% confidence interval, 0.48-2.30). Mild LAE was not associated with recurrent stroke. Moderate to severe LAE was an independent marker of recurrent cardioembolic or cryptogenic stroke in a multiethnic cohort of ischemic stroke patients. Further research is needed to determine whether anticoagulant use may reduce risk of recurrence in ischemic stroke patients with moderate to severe LAE