Marja Hedman

Introduction Cardiac organ damage (OD) is associated with increased risk of cardiovascular disease. However, limited knowledge exists on cardiac OD in young patients with cryptogenic ischaemic stroke (CIS). Aim To explore prevalence and covariates of cardiac OD in patients with CIS compared to controls participating in the SECRETO study. Methods We analysed data from 427 patients with CIS aged p < 0.01), while presence of LAE did not differ. In multivariable analyses, CIS was associated with presence of abnormal LV geometry (odds ratio 1.86 [95% confidence interval 1.09–3.20], p=0.024). In separate multivariable analyses in patients only, obesity was associated with both abnormal LV geometry and LAE (both p < 0.01), and higher systolic blood pressure only with presence of abnormal LV geometry (p < 0.001). No significant association with PFO was found. Conclusion In young patients with CIS participating in the SECRETO study, abnormal LV geometry was more prevalent compared to age- and sex-matched controls and associated with presence of higher blood pressure and obesity. The results point to the importance of blood pressure and weight control in CIS to prevent progression of cardiac OD and recurrent cardiovascular events. Graphical Abstract

Familial aggregation of stroke is well-documented, yet few studies have examined associations between stroke subtypes—particularly early-onset cryptogenic ischaemic stroke (eCIS)—and broader family history (FH) of cardiovascular disease. Such associations may provide insights into underlying etiologic mechanisms. In this multicentre case–control study, we included eCIS patients aged 18–49 years and matched stroke-free controls. We analysed the association between FH of stroke, venous thromboembolism (VTE), coronary artery disease (CAD), aneurysms and eCIS using multivariable logistic regression, with a subgroup analysis stratifying patients by high-risk patent foramen ovale (HR-PFO). We enrolled 508 eCIS patients (182 [36%] with HR-PFO) and 520 controls. Compared with controls, patients more frequently reported FH of stroke among first-degree relatives (FDR) (20% vs. 14%, P = .01) and grandparents (47% vs. 39%, P = .01), FH of early-onset stroke among FDR (5% vs. 2%, P = .01) and FH of early-onset VTE among FDR (5% vs. 2%, P = .003). In adjusted analyses, eCIS was associated with FH of stroke among FDR (OR 1.50; 95% CI, 1.04–2.16) and grandparents (1.50; 1.12–1.99), with FH of early-onset stroke among FDR (2.36; 1.11–5.04); and with FH of early-onset VTE among FDR (3.45; 1.47–8.13). eCIS was also associated with FH of VTE among FDR (1.80, 1.09–2.98) in the presence of HR-PFO. FH of CAD or aneurysms was not associated with eCIS. FH of stroke and VTE, particularly early-onset events and in the presence of HR-PFO, are associated with eCIS. These findings support familial predisposition and highlight prothrombotic mechanisms in eCIS. www.clinicaltrials.gov/study/NCT01934725

Background: Corresponding to impaired insulin response in skeletal muscle, insulin resistance may occur in the myocardium, suggesting a link between cardiometabolic disorders and cardiac glucose metabolism. We aimed to investigate whether cardiometabolic disorders predict myocardial [¹⁸F]fluorodeoxyglucose ([¹⁸F]FDG) uptake suppression in cardiac positron emission tomography / computed tomography (PET/CT) following a ketogenic diet and fasting. Results: The study included 100 patients undergoing [¹⁸F]FDG-PET/CT following a ketogenic diet of 1–2 days and a 12 h fast. Blood glucose, insulin, β-hydroxybutyrate (BHB), cholesterol, triglycerides and free fatty acid (FFA) levels were measured before [¹⁸F]FDG injection and later off-diet following overnight fast. The homeostatic model assessment–insulin resistance (HOMA-IR) value was calculated. Non-contrast computed tomography was used to assess the presence of fatty liver and visceral and subcutaneous fat areas. Suppression of myocardial [¹⁸F]FDG uptake was considered adequate if myocardial uptake was equal to or lower than the blood pool background. Compared to inadequate suppression, adequate suppression was associated with higher levels of BHB (median 0.26 mmol/l for inadequate and 0.43 mmol/l for adequate suppression, p = 0.004), FFA (0.58 mmol/l and 0.76 mmol/l respectively, p < 0.001), triglycerides (0.87 mmol/l and 1.12 mmol/l respectively, p = 0.028), and lower liver-spleen attenuation ratios (1.17 and 1.04 respectively, p = 0.013). Low HDL cholesterol, high triglycerides and off-diet HOMA-IR, as well as visceral adiposity, fatty liver and hypertension, predicted adequate suppression in men. Elevated BHB and FFA were significant predictors of adequate suppression in women. Conclusions: Cardiometabolic disorders are associated with lower myocardial [¹⁸F]FDG uptake. Insulin resistance and several other cardiometabolic risk factors are associated with attenuated uptake, especially in men. In women, factors reflecting metabolic response to a ketogenic diet and fasting have a more pronounced effect on myocardial [¹⁸F]FDG uptake.

BACKGROUND: The incidence of young-onset ischemic stroke is rising, driven by cryptogenic ischemic stroke (CIS) and patients without vascular risk factors. This study examines the burden and associations of modifiable traditional, nontraditional, and female sex–specific risk factors with young-onset CIS, stratified by clinically relevant patent foramen ovale (PFO), defined by high-risk features of atrial septal aneurysm or large right-to-left shunt. METHODS: We enrolled consecutive patients aged 18 to 49 years with recent CIS and frequency-matched stroke-free controls of the same age and sex from 19 European sites. Logistic regression assessed the association of risk factor counts (12 traditional, 10 nontraditional, 5 female sex–specific) and individual risk factors, stratified by PFO. Analyses were stratified by sex and age (18–39 and 40–49 years), with computation of population-attributable risk. RESULTS: We included 523 patients (median age, 41 years; 47.3% women; 196 [37.5%] with PFO) and 523 controls. In patients with CIS without PFO, each additional traditional (odds ratio, 1.417 [95% CI, 1.282–1.568]), nontraditional (odds ratio, 1.702 [95% CI, 1.338–2.164]), and female sex–specific risk factor (odds ratio, 1.700 [95% CI, 1.107.1–2.611]) increased CIS risk. For patients with CIS with PFO, each traditional risk factor increased the risk (odds ratio, 1.185 [1.057–1.328]), but only nontraditional risk factors remained significant when fully adjusted (odds ratio, 2.656 [2.036–3.464]). Population-attributable risks for CIS without PFO were 64.7%, 26.5%, and 18.9% for traditional, nontraditional, and female sex–specific risk factors. For CIS with PFO, population-attributable risks were 33.8%, 49.4%, and 21.8%, respectively. Migraine with aura was the most significant contributor, with population-attributable risks of 45.8% for CIS with PFO and 22.7% for CIS without PFO, showing a stronger impact in women. CONCLUSIONS: Despite the initial cryptogenic label of these strokes, traditional risk factors significantly contribute to CIS without PFO, while nontraditional factors seem more critical for CIS with PFO. Migraine with aura plays a prominent role in young-onset CIS development, particularly in women. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01934725.

Background: Inadequate myocardial glucose metabolism suppression (GMS) can hamper interpretation of cardiac [¹⁸F]fluorodeoxyglucose (FDG) positron emission tomography (PET/CT). Use of β-hydroxybutyrate (BHB) measurement before [¹⁸F]FDG injection has been proposed for predicting adequate GMS. However, limited information is available on BHB measurement in guiding preparations for [¹⁸F]FDG-PET/CT. The purpose of this study was to evaluate if point-of-care measured BHB is useful in guiding heparin premedication for cardiac [¹⁸F]FDG-PET/CT. Results: 155 patients (82 male) had followed a high-fat, low-carbohydrate diet and fasted for at least twelve hours. For the first 63 patients, BHB was measured, but it was not used to guide premedication. For the subsequent 92 patients, heparin 50 IU/kg was injected intravenously 15–20 min before [¹⁸F]FDG injection if the BHB level was low (< 0.35 mmol/l). Cardiac [¹⁸F]FDG uptake pattern was evaluated visually and [¹⁸F]FDG uptake in the myocardium and blood pool were measured. Median BHB level was 0.4 (range 0.1–5.8) mmol/l. Eighty-eight patients (57%) reached a BHB level higher than 0.35 mmol/l. 112 patients (72%) had adequate GMS. In the high BHB group, 74 patients (84%) had adequate GMS, whereas of those with low BHB, only 38 (57%) had adequate GMS (p < 0.001). In the low BHB group, the prevalence of inadequate GMS was comparable in patients with and without heparin (44% vs. 42%, p = 0.875). Conclusions: While high BHB predicts adequate GMS, unfractionated heparin does not improve GMS in patients with low BHB.

Introduction Central obesity (CO), characterized by an increased waist circumference increases the risk of cardiovascular disease (CVD) and morbidity, yet the underlying mechanisms are not fully understood. CO is often associated with general obesity, hypertension, and abnormal glucose tolerance, confounding the independent contribution of CO to CVD. Aim We investigated the relationship of CO (without associated disorders) with left ventricular (LV) characteristics and intrathoracic adipose tissue (IAT) by cardiac magnetic resonance. Methods LV characteristics, epicardial (EAT), and mediastinal adipose tissue (MAT) were measured from 29 normoglycemic, normotensive males with CO but without general obesity (waist circumference >100 cm, body mass index (BMI) 2) and 18 non-obese male controls. Results LV maximal wall thickness (LVMWT) and IAT but not LV mass or volumes were increased in CO subjects compared to controls (LVMWT, 12.3±1.2 vs. 10.7±1.5 mm, p < 0.001; EAT, 5.5±3.0 vs. 2.2±2.0 cm², p = 0.001; MAT, 31.0±12.8 vs. 15.4±10.7 cm², p < 0.001). The LVMWT was ≥12 mm in 69% of subjects with CO and 22% of controls (p = 0.002). In CO suspects, EAT correlated inversely with LV end-diastolic volume index (r = − 0.403, p = 0.037) and LV stroke volume (SV) (r = − 0.425, p = 0.027). MAT correlated inversely with SV (r = − 0.427, p=0.026) and positively with LVMWT (r = 0.399, p = 0.035). Among CO subjects, the waist-to-hip ratio (WHR) was an independent predictor of LVMWT (B = 22.4, β = 0.617, p < 0.001). The optimal cut-off with Youden’s index for LV hypertrophy was identified at WHR 0.98 (sensitivity 85%, specificity 89%). Conclusions CO independent of BMI is associated with LV hypertrophy and intrathoracic adipose tissue contributing to cardiovascular burden.

Background: Acute Stanford type A aortic dissection is a life-threatening condition that is challenging to predict and prevent. The risk for aortic dissection is known to increase with ascending aortic (AA) dilatation, which sets indication for preventive aortic replacement. Anyhow, most of the dissections occur before aortic diameter reaches the diameter indications of preventive surgery. Purpose: To investigate whether, alongside with aortic dilatation, AA elongation affects the increased risk for aortic dissection. Methods: This retrospective study included patients treated for Stanford type A aortic dissection (n=102), patients with AA dilatation (max. diameter > 40 mm) (n=134) and healthy controls (n=191). AA length and dimensions were measured from aortic computed tomography angiography (CTA) images. The AA length was defined as a distance between the aortic annulus to the origin of the brachiocephalic trunk. Results: AA length was significantly increased in patients with aortic dissection when compared to patients with AA dilatation and to healthy controls (106.2 ± 15.1 mm vs. 96.8 ± 11.2 mm vs. 82.5 ± 8.1 mm; p<0.001). After adjusting AA length to patient's height, BSA, sex and maximal diameter, adjusted length of AA was 99.8 mm in the dissection group, 94.4 mm in the AA dilatation group and 86.0 mm in healthy controls. Thus, when comparing adjusted AA length between the groups, dissected aortas were 13.8 mm longer than in healthy controls and 5.4 mm longer than in dilated non-dissected aortas (p<0.001). Dilated non-dissected aortas were 8.4 mm longer than in healthy controls (p<0.001). In the dissection cohort, 25/102 (24.5%) patients had maximal AA diameter 110 mm (Table). By combining 110 mm AA length and <55 mm diameter, 58% of the dissection patients would have been identified instead of using only AA diameter ≥55 mm as a cut-off criteria, based on which only 33% patients met the indication for elective surgery. Conclusions: To conclude, AA length seems to be a strong predictor of risk of type A aortic dissection and thus might be used as an additional tool in identifying patients for preventive surgery.Cut off - limits

The objective of this study was to investigate the incidence, treatment and survival of Stanford type B aortic dissection (BTAD) during 20 years in the Finnish population. Data collection was made from the Nationwide Care Register for Health Care, Finnish National Institute for Health and Welfare. All patients over 15 years of age with BTAD from 2000 to 2019 were included in the study. A data search of the Registry of Death Cause (Statistic Finland) was carried out to identify the date and cause of death. There were 1742 cases of BTAD during the study period. BTAD represented 45.6% of all aortic dissections leading to hospital admission. Incidence for BTAD was 1.62 per 100 000 inhabitants per year. The median survival was 12.7 years [95% confidence interval (CI) 9.63–14.7], 12.4 years (95% CI 10.5–14.4) and 8.6 years (95% CI 7.5–9.7) for patients treated with thoracic endovascular aortic repair (TEVAR), surgery and medical treatment (MT), respectively. Survival was significantly better after TEVAR and surgery, compared to MT only (P < 0.001). Age-adjusted survival was significantly better after TEVAR compared to patients treated with MT or surgery (hazard ratio 0.578, 95% CI 0.420–0.794, P < 0.001). Aortic-related death was the most common cause of death in all groups (41%). The incidence of BTAD seems to be similar in the Finnish population compared to other populational studies. Patients treated with TEVAR had significantly better survival compared to other patients. A high risk for late aortic-related death should be recognized in patients with BTAD.

Smooth muscle cells and endothelial cells have a remarkable level of plasticity in vascular pathologies. In thoracic and abdominal aortic aneurysms, smooth muscle cells have been suggested to undergo phenotypic switching and to contribute to degradation of the aortic wall structure in response to, for example, inflammatory mediators, dysregulation of growth factor signaling or oxidative stress. Recently, endothelial-to-mesenchymal transition, and a clonal expansion of degradative smooth muscle cells and immune cells, as well as mesenchymal stem–like cells have been suggested to contribute to the progression of aortic aneurysms. What are the factors driving the aortic cell phenotype changes and how vascular flow, known to affect aortic wall structure and to be altered in aortic aneurysms, could affect aortic cell remodeling? In this review, we summarize the current literature on aortic cell heterogeneity and phenotypic switching in relation to changes in vascular flow and aortic wall structure in aortic aneurysms in clinical samples with special focus on smooth muscle and endothelial cells. The differences between thoracic and abdominal aortic aneurysms are discussed.