IL-6 (interleukin-6) has important roles in atherosclerosis pathophysiology. To determine if anti-IL-6 therapy warrants evaluation as an adjuvant stroke prevention strategy in patients with carotid ...atherosclerosis, we tested whether circulating IL-6 levels predict carotid plaque severity, vulnerability, and progression in the prospective population-based CHS (Cardiovascular Health Study).
Duplex carotid ultrasound was performed at baseline and 5 years. Baseline plaque severity was scored 0 to 5 based on North American Symptomatic Carotid Endarterectomy Trial grade of stenosis. Plaque vulnerability at baseline was the presence of markedly irregular, ulcerated, or echolucent plaques. Plaque progression at 5 years was a ≥1 point increase in stenosis severity. The relationship of baseline plasma IL-6 levels with plaque characteristics was modeled using multivariable linear (severity) or logistic (vulnerability and progression) regression. Risk factors of atherosclerosis were included as independent variables. Stepwise backward elimination was used with
>0.05 for variable removal. To assess model stability, we computed the
-value or minimum strength of association (odds ratio scale) that unmeasured confounders must have with log IL-6 and the outcome to suppress the association. We performed internal validation with 100 bootstrap samples.
There were 4334 participants with complete data (58.9% women, mean age: 72.7±5.1 years), including 1267 (29.2%) with vulnerable plaque and 1474 (34.0%) with plaque progression. Log IL-6 predicted plaque severity (β=0.09,
=1.3×10
), vulnerability (OR, 1.21 95% CI, 1.05-1.40;
=7.4×10
,
-value=1.71), and progression (OR, 1.44 95% CI, 1.23-1.69,
=9.1×10
,
-value 2.24). In participants with >50% predicted probability of progression, mean log IL-6 was 0.54 corresponding to 2.0 pg/mL. Dichotomizing IL-6 levels did not affect the performance of prediction models.
Circulating IL-6 predicts carotid plaque severity, vulnerability, and progression. The 2.0 pg/mL cutoff could facilitate the selection of individuals that would benefit from anti-IL-6 drugs for stroke prevention.
Patients with minor stroke or transient ischemic attack (TIA), characterized as a brief episode of neurologic dysfunction caused by focal cerebral ischemia without infarction, have the least amount ...of disability and the most to lose should they have a stroke. Patients with vanishing symptoms may slip through our systems for detecting acute stroke owing either to patients’ delays in seeking medical attention or clinicians’ assessments that urgent treatment is not needed. This lost opportunity is even more worrisome given the tremendous improvements in the quality of primary and secondary stroke prevention that include evidence-based treatments with antiplatelet and oral anticoagulation . . .
Acute ischemic stroke affects men and women differently. In particular, women are often reported to experience higher acute stroke severity than men. We derived a low-dimensional representation of ...anatomical stroke lesions and designed a Bayesian hierarchical modeling framework tailored to estimate possible sex differences in lesion patterns linked to acute stroke severity (National Institute of Health Stroke Scale). This framework was developed in 555 patients (38% female). Findings were validated in an independent cohort (n = 503, 41% female). Here, we show brain lesions in regions subserving motor and language functions help explain stroke severity in both men and women, however more widespread lesion patterns are relevant in female patients. Higher stroke severity in women, but not men, is associated with left hemisphere lesions in the vicinity of the posterior circulation. Our results suggest there are sex-specific functional cerebral asymmetries that may be important for future investigations of sex-stratified approaches to management of acute ischemic stroke.
Carotid plaque is a subclinical measure of atherosclerosis. We have previously shown measures of carotid plaque to be heritable in a sample of 100 Dominican families and found evidence for linkage ...and association of common variants (CVs) on 7q36, 11p15, 14q32 and 15q23 with plaque presence. Our current study aimed to refine these regions further and identify rare variants (RVs) influencing plaque presence. Therefore, we performed targeted sequencing of the one LOD unit down region on 7q36, 11p15, 14q32 and 15q23 in 12 Dominican families with evidence for linkage to plaque presence. Gene-based RV analyses were performed using the Sequence Association Test for familial data (F-SKAT) under two filtering algorithms; 1. all exonic RVs and 2. non-synonymous RVs. Replication analyses were performed using a sample of 22 Dominican families and 556 unrelated Dominicans with Exome Array data. To identify additional non-synonymous RVs influencing plaque, we looked for co-segregation of RVs with plaque in each of the sequenced families. Our most strongly associated gene with evidence for replication was AMPD3 which showed suggestive association with plaque presence in the sequenced families (exonic RV p = 0.003, nonsynonymous RV p = 0.005) and replication families (exonic RV p = 0.04, nonsynonymous RV p = 0.02). Examination of the sequenced family pedigrees revealed two missense variants on chromosome 11 which co-segregated with plaque presence in one of our families; rs61751342 (located in DENND2B), and rs61760882 (located in RNF141). The rs61751342 missense variant is an eQTL for SCUBE2 in the atrial appendage. Notably, SCUBE2 encodes a protein which interacts with vascular endothelial growth factor (VEGF) receptor 2 to regulate VEGF-induced angiogenesis, thus providing biologic plausibility for this gene in atherosclerosis. In conclusion, using targeted sequencing of previously-identified linkage regions, we have identified suggestive evidence for the role of RVs in carotid plaque pathogenesis.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVEChronic infections, including periodontal infections, may predispose to cardiovascular disease. We investigated the relationship between periodontal microbiota and hypertension.
METHODS AND ...RESULTSSix hundred and fifty-three dentate men and women with no history of stroke or myocardial infarction were enrolled in INVEST. We collected 4533 subgingival plaque samples (average of seven samples per participant). These were quantitatively assessed for 11 periodontal bacteria using DNA–DNA checkerboard hybridization. Cardiovascular risk factor measurements were obtained. Blood pressure and hypertension (SBP ≥140 mmHg, DBP ≥90 mmHg or taking antihypertensive medication, or self-reported history) were each regressed on the level of bacteriaconsidered causative of periodontal disease (etiologic bacterial burden); associated with periodontal disease (putative bacterial burden); and associated with periodontal health (health-associated bacterial burden). All analyses were adjusted for age, race/ethnicity, sex, education, BMI, smoking, diabetes, low-density lipoprotein and high-density lipoprotein cholesterol. Etiologic bacterial burden was positively associated with both blood pressure and prevalent hypertension. Comparing the highest and lowest tertiles of etiologic bacterial burden, SBP was 9 mmHg higher, DBP was 5 mmHg higher (P for linear trend was less than 0.001 in each case), and the odds ratio for prevalent hypertension was 3.05 (95% confidence interval 1.60–5.82) after multivariable adjustment.
CONCLUSIONOur data provide evidence of a direct relationship between the levels of subgingival periodontal bacteria and both SBP and DBP as well as hypertension prevalence.
Background Nature exposures may be associated with reduced risk of heart disease. The present study examines the relationship between objective measures of neighborhood greenness (vegetative ...presence) and 4 heart disease diagnoses (acute myocardial infarction, ischemic heart disease, heart failure, and atrial fibrillation) in a population-based sample of Medicare beneficiaries. Methods and Results The sample included 249 405 Medicare beneficiaries aged 65 years and older whose location ( ZIP +4) in Miami-Dade County, Florida, did not change from 2010 to 2011. Analyses examined relationships between greenness, measured by mean block-level normalized difference vegetation index from satellite imagery, and 4 heart disease diagnoses. Hierarchical regression analyses, in a multilevel framework, assessed the relationship of greenness to each heart disease diagnosis, adjusting successively for individual sociodemographics, neighborhood income, and biological risk factors (diabetes mellitus, hypertension, and hyperlipidemia). Higher greenness was associated with reduced heart disease risk, adjusting for individual sociodemographics and neighborhood income. Compared with the lowest tertile of greenness, the highest tertile of greenness was associated with reduced odds of acute myocardial infarction by 25% (odds ratio, 0.75; 95% CI , 0.63-0.90), ischemic heart disease by 20% (odds ratio, 0.80; 95% CI , 0.77-0.83), heart failure by 16% (odds ratio, 0.84; 95% CI , 0.80-0.88), and atrial fibrillation by 6% (odds ratio, 0.94; 95% CI , 0.87-1.00). Associations were attenuated after adjusting for biological risk factors, suggesting that cardiometabolic risk factors may partly mediate the greenness to heart disease relationships. Conclusions Neighborhood greenness may be associated with reduced heart disease risk. Strategies to increase area greenness may be a future means of reducing heart disease at the population level.
PDF
