Prevalence and vascular risk factors of basal ganglia calcifications in patients at risk for cerebrovascular disease.

BACKGROUND AND PURPOSE: Risk factors for and meaning of basal ganglia calcifications outside Fahr syndrome are poorly understood. We aimed to assess the prevalence of basal ganglia calcifications and the association with vascular risk factors. MATERIALS AND METHODS: 1133 patients suspected of acute ischemic stroke from the Dutch acute stroke (DUST) study who underwent thin-slice unenhanced brain CT were analyzed. Basal ganglia calcifications were scored bilaterally as absent, mild (dot), moderate (multiple dots or single artery) and severe (confluent). Uni- and multivariable logistic regression analysis was used to determine possible risk factors (age, gender, history of stroke, smoking, hypertension, diabetes mellitus, hyperlipidemia, body mass index (BMI), renal function and family history of cardiovascular disease under 60 years) for presence of basal ganglia calcifications and ordinal regression analysis for severity of basal ganglia calcifications. RESULTS: Mean age was 67.4 years (SD: 13.8), 56.8% were male. 337 (29.7%) patients had basal ganglia calcifications, of which 196 (58%) were mild, 103 (31%) moderate, 38 (11%) severe. In multivariable logistic regression analysis, age (OR: 1.02, 95% CI 1.01-1.03, P < 0.01) and BMI (OR: 0.95, 95% CI 0.91-0.98, p 0.01) were significantly associated with the presence of basal ganglia calcifications. Ordinal regression analysis gave comparable results. Age (OR: 1.02, 95% CI 1.01-1.03, P < 0.01) and BMI (OR: 0.95, 95% CI 0.92-0.99, P 0.01) were significantly associated with severity of basal ganglia calcifications. CONCLUSIONS: In this study with patients suspected of acute ischemic stroke, basal ganglia calcifications were common and significantly associated with older age and lower BMI.

Relation between resting amygdalar activity and cardiovascular events: a longitudinal and cohort study.

BACKGROUND: Emotional stress is associated with increased risk of cardiovascular disease. We imaged the amygdala, a brain region involved in stress, to determine whether its resting metabolic activity predicts risk of subsequent cardiovascular events. METHODS: Individuals aged 30 years or older without known cardiovascular disease or active cancer disorders, who underwent 18F-fluorodexoyglucose PET/CT at Massachusetts General Hospital (Boston, MA, USA) between Jan 1, 2005, and Dec 31, 2008, were studied longitudinally. Amygdalar activity, bone-marrow activity, and arterial inflammation were assessed with validated methods. In a separate cross-sectional study we analysed the relation between perceived stress, amygdalar activity, arterial inflammation, and C-reactive protein. Image analyses and cardiovascular disease event adjudication were done by mutually blinded researchers. Relations between amygdalar activity and cardiovascular disease events were assessed with Cox models, log-rank tests, and mediation (path) analyses. FINDINGS: 293 patients (median age 55 years [IQR 45·0-65·5]) were included in the longitudinal study, 22 of whom had a cardiovascular disease event during median follow-up of 3·7 years (IQR 2·7-4·8). Amygdalar activity was associated with increased bone-marrow activity (r=0·47; p<0·0001), arterial inflammation (r=0·49; p<0·0001), and risk of cardiovascular disease events (standardised hazard ratio 1·59, 95% CI 1·27-1·98; p<0·0001), a finding that remained significant after multivariate adjustments. The association between amygdalar activity and cardiovascular disease events seemed to be mediated by increased bone-marrow activity and arterial inflammation in series. In the separate cross-sectional study of patients who underwent psychometric analysis (n=13), amygdalar activity was significantly associated with arterial inflammation (r=0·70; p=0·0083). Perceived stress was associated with amygdalar activity (r=0·56; p=0·0485), arterial inflammation (r=0·59; p=0·0345), and C-reactive protein (r=0·83; p=0·0210). INTERPRETATION: In this first study to link regional brain activity to subsequent cardiovascular disease, amygdalar activity independently and robustly predicted cardiovascular disease events. Amygdalar activity is involved partly via a path that includes increased bone-marrow activity and arterial inflammation. These findings provide novel insights into the mechanism through which emotional stressors can lead to cardiovascular disease in human beings. FUNDING: None.

Arterial calcification and long-term outcome in chronic limb-threatening ischemia patients.

PURPOSE: Within five years after presentation 50-60% of patients with chronic limb-threatening ischemia (CLI) have died or had an amputation. We assessed the predictive value of lower extremity arterial calcification on computed tomography (CT) characteristics on both 7-years amputation-free survival and 10-years all-cause mortality in patients with CLI. METHOD: Included were 89 CLI patients (mean age 73.1 ±â€¯11.6 years) who underwent a CT angiography of the lower extremities. In the femoropopliteal and crural arteries based on a CT score the following calcification characteristics were assessed: severity, annularity, thickness and continuity. The predictive value of different arterial calcification characteristics was analysed by age- and sex-adjusted multivariate Cox regression analysis. RESULTS: Complete annular calcifications were common (femoropopliteal 43.7%, n = 38; crural, 63.2%, n = 55). Mean survival was 278.4 weeks (95% CI 238.77-318.0 weeks). Patients with complete annular calcifications had a higher all-cause 10-year mortality (femoropopliteal unadjusted HR 1.64, p = 0.04 and adjusted for age and sex HR 1.68, p = 0.04; crural unadjusted HR 1.92, p = 0.02, adjusted for age and sex HR 2.29, p = 0.006) than patients with other calcification characteristics. CONCLUSIONS: Annularity of calcification of both femoropopliteal and crural arteries is a predictor for 10-year all-cause survival, its hazard being even higher than the traditional prognostic risk factors for CLI and therefore could be involved in the poor survival of these patients.

Early detection of small volume stroke and thromboembolic sources with computed tomography: Rationale and design of the ENCLOSE study.

BACKGROUND: Computed tomography is the most frequently used imaging modality in acute stroke imaging protocols. Detection of small volume infarcts in the brain and cardioembolic sources of stroke is difficult with current computed tomography protocols. Furthermore, the role of computed tomography findings to predict recurrent ischemic stroke is unclear. With ENCLOSE, we aim to improve (1) the detection of small volume infarcts with thin slice computed tomography perfusion (CTP) images and thromboembolic source with cardiac computed tomography techniques in the acute stage of ischemic stroke and (2) prediction of recurrent ischemic stroke with computed tomography-derived predictors.Methods/design: ENCLOSE is a prospective multicenter observational cohort study, which will be conducted in three Dutch stroke centers (ClinicalTrials.gov Identifier: NCT04019483). Patients (≥18 years) with suspected acute ischemic stroke who undergo computed tomography imaging within 9 h after symptom onset are eligible. Computed tomography imaging includes non-contrast CT, CTP, and computed tomography angiography (CTA) from base of the heart to the top of the brain. Dual-energy CT data will be acquired when possible, and thin-slice CTP reconstructions will be obtained in addition to standard 5 mm CTP data. CTP data will be processed with commercially available software and locally developed model-based methods. The post-processed thin-slice CTP images will be compared to the standard CTP images and to magnetic resonance diffusion-weighted imaging performed within 48 h after admission. Detection of cardioembolic sources of stroke will be evaluated on the CTA images. Recurrence will be evaluated 90 days and two years after the index event. The added value of imaging findings to prognostic models for recurrent ischemic stroke will be evaluated. CONCLUSION: The aim of ENCLOSE is to improve early detection of small volume stroke and thromboembolic sources and to improve prediction of recurrence in patients with acute ischemic stroke.