Cerebral Small-Vessel Disease in Individuals with a Family History of Coronary Heart Disease: The Atherosclerosis Risk in Communities Study

<b><i>Introduction:</i></b> The degree to which a family history of coronary heart disease (FHCHD) is associated with silent cerebral small-vessel disease (cSVD) among healthy adults, independent of prevalent CHD and traditional risk factors, is unknown. <b><i>Methods:</i></b> The Atherosclerosis Risk in Communities (ARIC) study is a community-based cohort study with self-reported family history data and brain magnetic resonance imaging (ages 68–88). The association between markers of cSVD (lacunar infarcts and cerebral microbleeds), or log-transformed white matter hyperintensity (WMH) volume, and FHCHD, or the number of affected relatives was examined using separate adjusted logistic or linear regression models, respectively. Race interaction terms were evaluated. <b><i>Results:</i></b> Of 1,639 participants without prevalent CHD (76 ± 5 years, 62% female, 29% black), 686 (42%) had FHCHD. There were higher odds of lacunar infarct (OR 1.40, 95% CI 1.07–1.84) among those with parental FHCHD and higher odds of microhemorrhages (lobar OR 1.86, 95% CI 1.13–3.06; subcortical OR 1.47, 95% CI 1.01–2.15) among those with sibling FHCHD. A greater number of any relative affected was associated with higher odds of lacunar infarct (OR 1.24, 95% CI 1.04–1.47) and lobar microhemorrhages (OR 1.31, 95% CI 1.05–1.64) but not subcortical microhemorrhages (OR 1.09, 95% CI 0.92–1.28). Odds of having a lacunar infarct were higher among blacks (p-interaction 0.04) with paternal FHCHD (OR 2.20, CI 1.35–3.58) than whites with paternal FHCHD (OR 1.17, CI 0.87–1.56). There was no association with WMH. <b><i>Discussion/Conclusion:</i></b> Markers of cSVD, specifically lacunar infarcts and microhemorrhages, appear to be associated with FHCHD, potentially representing shared mechanisms in different vascular beds, and perhaps a genetic propensity for vascular disease.

Abstract MP26: Silent Small-vessel Cerebrovascular Disease In Individuals With A Family History Of Coronary Heart Disease: The Atherosclerosis Risk In Communities (ARIC) Study

Background: It is established that a family history of coronary heart disease (FHCHD) is associated with coronary atherosclerosis in healthy first-degree relatives, but the extent to which FHCHD is associated with silent cerebrovascular disease (cSVD) is unknown. We hypothesized a higher prevalence of cSVD in healthy persons with FHCHD, independent of traditional risk factors, compared to those without FHCHD. Methods: ARIC is a community-based cohort study with self-reported family history data and brain magnetic resonance imaging (visit 5; 2011-13). The association between binary markers of cSVD (lacunar infarcts and/or cerebral microbleeds), or log-transformed white matter hyperintensity volume (WMH), and FHCHD (parent and/or sibling), or number of relatives was examined using separate adjusted multivariable logistic or linear regression models respectively. Sensitivity analysis (N=183) excluded prevalent CHD. Race interaction terms were included. Results: Of 1828 participants (76±5yo, 60% female, 28% black), 787 had FHCHD (699 parental, 209 sibling FHCHD). There were increased adjusted odds of lacunar infarct among those with parental FHCHD (Table). An increased odds of cerebral microbleeds were seen among those with sibling history but not parental. Effect estimates were similar when excluding those with prevalent CHD (Table). Greater number of siblings affected was associated with higher odds of lacunar infarct (OR 1.35, CI 1.04-1.74), lobar (OR 1.53, CI 1.12-2.09) and subcortical microbleeds (OR 1.30, CI 1.01-1.66). Odds of a lacunar infarct being present were higher among blacks (p-interaction 0.04) with paternal FHCHD (OR 2.20, CI 1.35-3.58) compared to whites (OR 1.17, CI 0.87-1.56). Neither FHCHD nor number of affected relatives was associated with WMH. Conclusions: Our results suggest that some cSVD manifestations are associated with FHCHD, potentially representing shared mechanisms in different vascular beds, and perhaps a genetic propensity for vascular disease.

Abstract P661: Atheromatous Disease of the Parent Artery is Common in Patients With Lacunar Infarcts

Background: Perforator disease caused by parent artery atheromatous disease is one of the mechanisms implicated in the pathogenesis of lacunar infarcts, but there is limited data on its prevalence. We sought to determine the prevalence of parent vessel atheromatous disease in patients with lacunar infarcts. Methods: This is a retrospective study of consecutive patients with lacunar strokes admitted to NYU Langone Medical Center and Brown University from 2017-2019. Lacunar infarct was defined as subcortical infarct <1.5cm on CT or <2cm on diffusion-weighted imaging without significant stenosis (>50%) in the parent vessel and no cardioembolic source. Non-invasive imaging (CTA or MRA) was reviewed by a neuroradiologist or a vascular neurologist to determine the presence or absence of stenosis (< 50%) or luminal irregularity without stenosis in the stem artery segment at the location of the perforator corresponding to the infarct. Patients were divided into two groups: luminal irregularity/stenosis vs. none. We compared clinical and radiographic characteristics and rates of neurological deterioration between the two groups. Results: Among 208 patients with lacunar infarcts (mean age 68.9±11.9 years, 40.9% women, 61.1% White, 13.9% Black, and 12.5% Hispanic), 42 (20.2%) had luminal stenosis and 90 (43.3%) had luminal irregularity without stenosis. Baseline characteristics and prevalence of risk factors were similar between the two groups. Patients with luminal irregularity/stenosis had longer median infarct diameter (10.6 mm vs 8.7 mm, p=0.007). Other imaging variables such as the presence of prior lacunar infarcts and white matter disease burden assessed by Fazekas Score were not significantly different between the two groups. The rate of any neurological deterioration after admission was similar between the two groups (22.7% vs. 15.8%, p=0.283). Conclusion: In this multi-ethnic population, nearly two-thirds of patients with a lacunar infarct were found to have luminal irregularity or stenosis in the parent artery corresponding to the infarct, implying a potential atherosclerotic mechanism. Future studies are needed using advanced imaging of the stem artery to define plaque characteristics which may help determine the underlying mechanism.

Abstract P674: Markers of Atherosclerotic Disease but Not Small Vessel Disease Predict Neurologic Deterioration in Acute Lacunar Strokes

Introduction: Neurologic deterioration (ND) occurs in a quarter of acute lacunar infarct patients and may lead to severe disability. The underlying pathophysiology of ND in these patients is not clearly understood. We sought to identify risk factors and clinical characteristics associated with ND. Methods: This retrospective study included consecutive patients admitted to NYU Langone Medical Center and Brown University for lacunar-type strokes from 2017-2019. Lacunar infarct was defined as subcortical infarct <1.5cm on CT or <2cm on diffusion-weighted imaging without significant stenosis (>50%) in the parent vessel and no cardioembolic source. Available non-invasive imaging (CTA or MRA) was reviewed by a neuroradiologist or vascular neurologist to determine the presence or absence of stenosis (<50%) or luminal irregularity without stenosis in the stem artery segment at the location of the perforator corresponding to the infarct. Fazekas score was determined from available MRI T2 images. We defined ND as those with any neurologic deterioration during their hospitalization referable to lacunar stroke and not related to a medical or non-cerebrovascular neurological complication. We compared clinical and radiographic characteristics of those with and without ND. Results: Among 242 lacunar stroke patients (mean age 68.9±12.2 years, 43.8% women, 61.2% white, 12.8% black, and 13.2% Hispanic), we identified 46 (19%) with ND. There were no demographic differences between those with and without ND. Those with ND were more likely to have systemic atherosclerotic disease (34.8% vs 19.9%, p=0.049) and higher low-density lipoprotein (111 vs 100 mg/dL, p=0.034). Those with ND had less white matter disease on MRI (lower Fazekas score) and were less likely to have chronic lacunes than those without ND. We did not find any association between radiographic subclinical perforator atherosclerotic disease and ND (odds ratio [95% confidence interval]: 1.83 [0.81-4.14], p=0.147). Conclusions: In this multi-ethnic population, patients with neurologic deterioration following an acute lacunar stroke were more likely to have markers of atherosclerotic disease and less likely to have imaging findings suggestive of chronic small vessel disease.