Neutrophil-to-Lymphocyte Ratio Is an Independent Risk Factor for Coronary Artery Disease in Central Obesity.

Several inflammatory biomarkers were found to be associated with an increased risk of cardiovascular disease. Neutrophil-to-lymphocyte ratio (NLR) is a marker of subclinical inflammation that increases with the stress response. Visceral adiposity index (VAI) calculated as a combination of anthropometric and metabolic parameters reflects both the extent and function of visceral adipose tissue. Given the association of subclinical inflammation with both obesity and cardiovascular diseases, it is plausible that the inflammation-CVD association is modulated by the amount and function of adipose tissue. Thus, our aim was to examine the association between NLR and coronary artery calcium score (CACS), an intermediate marker of coronary artery disease in asymptomatic patients across VAI tertiles. Methods: Data from 280 asymptomatic participants of a cardiovascular screening program were analysed. In addition to the collection of lifestyle and medical history, a non-contrast cardiac CT scan and laboratory tests were performed on all participants. Multivariate logistic regression was conducted with CACS > 100 as the outcome and with conventional cardiovascular risk factors and NLR, VAI, and NLR by VAI tertile as predictors. Results: We found an interaction between VAI tertiles and NLR; NLR values were similar in the lower VAI tertiles, while they were higher in the CACS > 100 in the 3rd VAI tertile (CACS ≤ 100: 1.94 ± 0.58 vs. CACS > 100: 2.48 ± 1.1, p = 0.008). According to multivariable logistic regression, the interaction between NLR and VAI tertiles remained: NLR was associated with CACS > 100 in the 3rd VAI tertile (OR = 1.67, 95% CI 1.06-2.62, p = 0.03) but not in the lower tertiles even after adjustment for age, sex, smoking, history of hypertension, hyperlipidaemia, and diabetes mellitus, as well as high-sensitivity C-reactive protein. Our findings draw attention to the independent association between subclinical, chronic, systemic inflammation and subclinical coronary disease in obesity.

Overlapping Genetic Background of Coronary Artery and Carotid/Femoral Atherosclerotic Calcification.

BACKGROUND AND OBJECTIVES: Multivessel atherosclerosis and its genetic background are under-investigated, although atherosclerosis is seldom local and still causes high mortality. Alternative methods to assess coronary calcification (CAC) might incorporate genetic links between different arteries' atherosclerotic involvement, however, co-occurrences of coronary calcification have not been investigated in twins yet. MATERIALS AND METHODS: We assessed the heritability of radio morphologically distinct atherosclerotic plaque types in coronary (non-enhanced CT, Agatston score), carotid, and femoral arteries (B-mode ultrasound) in 190 twin subjects (60 monozygotic, 35 dizygotic pairs). Four-segment scores were derived in order to assess the dissemination of the distinct plaque types in the carotid and femoral arteries taking bilaterality into account. We calculated the genetic correlation between phenotypically correlating plaque types in these arteries. RESULTS: CAC and dissemination of calcified plaques in the carotid and femoral arteries (4S_hyper) were moderately heritable (0.67 [95% CI: 0.37-1] and 0.69 [95% CI: 0.38-1], respectively) when adjusted for age and sex. Hypoechoic plaques in the carotid and femoral arteries showed no heritability, while mixed plaques showed intermediate heritability (0.50 [95% CI: 0-0.76]). Age and sex-adjusted phenotypic correlation between CAC and 4segm_hyper was 0.48 [95% CI: 0.30-0.63] and the underlying genetic correlation was 0.86 [95% CI: 0.42-1]. CONCLUSIONS: Calcification of atherosclerotic plaques is moderately heritable in all investigated arteries and significant overlapping genetic factors can be attributed to the phenotypical resemblance of coronary and carotid or femoral atherosclerotic calcification. Our findings support the idea of screening extracoronary arteries in asymptomatic individuals. We also propose a hypothesis about primarily carotid-coronary and femoral-coronary atherosclerosis as two distinct genetic predispositions to co-localization.

Association between coronary atherosclerosis and visceral adiposity index.

BACKGROUND AND AIMS: Visceral obesity is a marker of dysfunctional adipose tissue and ectopic fat infiltration. Many studies have shown that visceral fat dysfunction has a close relationship with cardiovascular disease. For a better identification of visceral adiposity dysfunction, the visceral adiposity index (VAI) is used. Coronary artery calcium score (CACS) is known to have a strong correlation with the total plaque burden therefore provides information about the severity of the coronary atherosclerosis. CACS is a strong predictor of cardiac events and it refines cardiovascular risk assessment beyond conventional risk factors. Our aim was to evaluate the association between VAI and CACS in an asymptomatic Caucasian population. METHODS AND RESULTS: Computed tomography scans of 460 participants were analyzed in a cross-sectional, voluntary screening program. A health questionnaire, physical examination and laboratory tests were also performed. Participants with a history of cardiovascular disease were excluded from the analysis. Mean VAI was 1.41 ± 0.07 in men and 2.00 ± 0.15 in women. VAI showed a positive correlation with total coronary calcium score (r = 0.242) in males but not in females. VAI was stratified into tertiles by gender. In males, third VAI tertile was independently associated with CACS>100 (OR: 3.21, p = 0.02) but not with CACS>0 after the effects of conventional risk factors were eliminated. CONCLUSION: VAI tertiles were associated with calcium scores and the highest VAI tertile was an independent predictor for the presence of CACS>100 in males but not in females.

Comprehensive coronary plaque assessment in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is associated with an increased risk of cardiovascular disease. Previous studies have assessed the relationship between OSA and coronary artery disease (CAD) using coronary artery calcium score (CAC) measurements. However, limited data are available regarding the association of OSA with non-calcified plaque burden. We therefore aimed to assess the relationship between CAD severity as assessed by coronary computed tomography angiography (CTA) and OSA. Forty-one adult subjects (59 ± 9 years, 15 men) underwent a 256-slice coronary CTA, which was followed by a diagnostic attended cardiorespiratory polygraphy (n = 13) or polysomnography (n = 28). Segment involvement score (SIS), segment stenosis score (SSS) and CAC were used to quantify total CAD burden. Correlation analysis was used to assess potential associations between CAD and OSA. Twenty-two patients were diagnosed with OSA. SIS and SSS were elevated in OSA (2.90 ± 2.78 versus 1.79 ± 2.39 and 4.91 ± 5.94 versus 1.79 ± 4.54, OSA versus controls, SIS and SSS respectively, both p < 0.01) and correlated with OSA severity as measured by the apnea-hypopnea index (AHI, r = 0.41 and 0.43, p < 0.01) and oxygen desaturation index (ODI, r = 0.45 and 0.46, p < 0.01). However, no significant correlation was observed between CAC and OSA. Compared to CAC, SIS and SSS provide additional information on coronary plaque burden in OSA, which shows a significant association with OSA.

The effect of four-phasic versus three-phasic contrast media injection protocols on extravasation rate in coronary CT angiography: a randomized controlled trial.

OBJECTIVES: Contrast media (CM) extravasation is a well-known complication of CT angiography (CTA). Our prospective randomized control study aimed to assess whether a four-phasic CM administration protocol reduces the risk of extravasation compared to the routinely used three-phasic protocol in coronary CTA. METHODS: Patients referred to coronary CTA due to suspected coronary artery disease were included in the study. All patients received 400 mg/ml iomeprol CM injected with dual-syringe automated injector. Patients were randomized into a three-phasic injection-protocol group, with a CM bolus of 85 ml followed by 40 ml of 75%:25% saline/CM mixture and 30 ml saline chaser bolus; and a four-phasic injection-protocol group, with a saline pacer bolus of 10 ml injected at a lower flow rate before the three-phasic protocol. RESULTS: 2,445 consecutive patients were enrolled (mean age 60.6 ± 12.1 years; females 43.6%). Overall rate of extravasation was 0.9% (23/2,445): 1.4% (17/1,229) in the three-phasic group and 0.5% (6/1,216) in the four-phasic group (p = 0.034). CONCLUSIONS: Four-phasic CM administration protocol is easy to implement in the clinical routine at no extra cost. The extravasation rate is reduced by 65% with the application of the four-phasic protocol compared to the three-phasic protocol in coronary CTA. KEY POINTS: • Four-phasic CM injection-protocol reduces extravasation rate by 65% compared to three-phasic. • The saline pacer bolus substantially reduces the risk of CM extravasation. • The implementation of four-phasic injection-protocol is at no cost.

Aortic root dimensions are predominantly determined by genetic factors: a classical twin study.

OBJECTIVES: Previous studies using transthoracic echocardiography (TTE) observed moderate heritability of aortic root dimensions. Computed tomography angiography (CTA) might provide more accurate heritability estimates. Our primary aim was to assess the heritability of the aortic root with CTA. Our secondary aim was to derive TTE-based heritability and compare this with the CTA-based results. METHODS: In the BUDAPEST-GLOBAL study 198 twin subjects (118 monozygotic, 80 dizygotic; age 56.1 ± 9.4 years; 126 female) underwent CTA and TTE. We assessed the diameter of the left ventricular outflow tract (LVOT), annulus, sinus of Valsalva, sinotubular junction and ascending aorta. Heritability was assessed using ACDE model (A additive genetic, C common environmental, D dominant genetic, E unique environmental factors). RESULTS: Based on CTA, additive genetic effects were dominant (LVOT: A = 0.67, E = 0.33; annulus: A = 0.76, E = 0.24; sinus of Valsalva: A = 0.83, E = 0.17; sinotubular junction: A = 0.82, E = 0.18; ascending aorta: A = 0.75, E = 0.25). TTE-derived measurements showed moderate to no genetic influence (LVOT: A = 0.38, E = 0.62; annulus: C = 0.47, E = 0.53; sinus of Valsalva: C = 0.63, E = 0.37; sinotubular junction: C = 0.45, E = 0.55; ascending aorta: A = 0.67, E = 0.33). CONCLUSION: CTA-based assessment suggests that aortic root dimensions are predominantly determined by genetic factors. TTE-based measurements showed moderate to no genetic influence. The choice of measurement method has substantial impact on heritability estimates. KEY POINTS: • Aortic root dimensions are determined by genetic and environmental effects. • Transthoracic echocardiography (TTE) demonstrated moderate to no genetic effects on aortic root dimensions. • Computed tomography angiography might provide more accurate heritability estimates compared to TTE. • Three-dimensional imaging techniques are needed to reliably quantify aortic root dimensions.

Long-term prognostic value of left atrial longitudinal strain in an elderly community-based cohort.

Despite the well-known importance of left atrial (LA) mechanics in diastolic function, data are scarce regarding the prognostic power of LA longitudinal strain and its potential added value in the risk stratification of an elderly population. Accordingly, our aim was to determine the long-term prognostic importance of 2D speckle-tracking echocardiography-derived peak atrial longitudinal strain (PALS) in a community-based screening sample. Three hundred and fourteen volunteers were retrospectively identified from a population-based screening program (mean age 62 ± 11 years; 58% female) with a median follow-up of 9.5 years. All subjects who participated in the screening program underwent 2D echocardiography to measure left ventricular (LV) ejection fraction (EF), global longitudinal strain (GLS), and PALS, as well as low-dose cardiac CT to determine the Agatston score. The primary endpoint was all-cause mortality. Thirty-nine subjects (12.4%) met the primary endpoint. Subjects with adverse outcomes had significantly lower LV GLS (dead vs. alive; - 19.2 ± 4.3 vs. - 20.6 ± 3.5%, p < 0.05) and PALS (32.3 ± 12.0 vs. 41.8 ± 14.2%, p < 0.001), whereas LV EF did not show a difference between the two groups (51.1 ± 7.0 vs. 52.1 ± 6.2, %, p = NS). By multivariable Cox regression analysis, PALS was found to be a significant predictor of adverse outcomes independent of LV GLS, and Agatston and Framingham scores. In subjects with PALS values below the standard cut-off of 39%, the risk of all-cause mortality was almost 2.5 times higher (hazard ratio: 2.499 [95% confidence interval: 1.334-4.682], p < 0.05). Beyond the assessment of LV EF and LV GLS, PALS offers incremental value in cardiovascular risk stratification in a community-based elderly cohort. PALS was found to be a significant and independent predictor of long-term mortality among other classical cardiovascular risk estimators.

Dynamic Perfusion Computed Tomography for the Assessment of Concomitant Coronary Artery Disease in Patients with a History of Percutaneous Transluminal Angioplasty for Chronic Limb-Threatening Ischemia-A Pilot Study.

BACKGROUND: Chronic limb-threatening ischemia (CLTI) is associated with high rates of long-term cardiovascular mortality. Exercise stress testing to detect obstructive coronary artery disease (CAD) can be difficult in this subset of patients due to inability to undergo exercise testing, presence of balanced ischemia and severe coronary artery calcification (CAC). AIM: To test the feasibility of regadenoson stress dynamic perfusion computed tomography (DPCT) in CLTI patients. METHODS: Between 2018 and 2023, coronary computed tomography angiography (CTA) and, in the case of a calcium score higher than 400, DPCT, were performed in 25 CLTI patients with a history of endovascular revascularization. RESULTS: Of the 25 patients, 19 had a calcium score higher than 400, requiring DPCT image acquisition. Obstructive CAD could be ruled out in 10 of the 25 patients. Of the 15 CTA/DPCT+ patients, 13 proceeded to coronary angiography (CAG). Revascularization was necessary in all 13 patients. In these 13 patients, vessel-based sensitivity and specificity of coronary CTA/DPCT as compared to invasive evaluation was 75%, respectively. At follow-up (27 ± 21 months) there was no statistically significant difference in all-cause mortality between CTA/DPCT- positive and -negative patients (p = 0.065). CONCLUSIONS: Despite a high prevalence of severe CAC, coronary CTA complemented by DPCT may be a feasible method to detect obstructive and functionally significant CAD in CLTI patients.

Coronary CT-based FFR in patients with acute myocardial infarction might predict follow-up invasive FFR: The XPECT-MI study.

BACKGROUND: We aimed to evaluate whether invasive fractional flow reserve (FFRi) of non-infarction related (non-IRA) lesions changes over time in ST-elevation myocardial infarction (STEMI) patients. Moreover, we assessed the diagnostic performance of coronary CT angiography-derived FFR(FFRCT) following the index event in predicting follow-up FFRi. METHODS: We prospectively enrolled 38 STEMI patients (mean age 61.6 â€‹± â€‹9 years, 23.1% female) who underwent non-IRA baseline and follow-up FFRi measurements and a baseline FFRCT (within ≤10 days after STEMI). Follow-up FFRi was performed at 45-60 days (FFRi and FFRCT value of ≤0.8 was considered positive). RESULTS: FFRi values showed significant difference between baseline and follow-up (median and interquartile range (IQR) 0.85 [0.78-0.92] vs. 0.81 [0.73-0.90] p â€‹= â€‹0.04, respectively). Median FFRCT was 0.81 [0.68-0.93]. In total, 20 lesions were positive on FFRCT. A stronger correlation and smaller bias were found between FFRCT and follow-up FFRi (ρ â€‹= â€‹0.86,p â€‹< â€‹0.001,bias:0.01) as compared with baseline FFRi (ρ â€‹= â€‹0.68, p â€‹< â€‹0.001,bias:0.04). Comparing follow-up FFRi and FFRCT, no false negatives but two false positive cases were found. The overall accuracy was 94.7%, with sensitivity and specificity of 100.0% and 90.0% for identifying lesions ≤0.8 on FFRi. Accuracy, sensitivity, and specificity were 81.5%, 93.3%, and 73.9%, respectively, for identifying significant lesions on baseline FFRi using index FFRCT. CONCLUSION: FFRCT in STEMI patients close to the index event could identify hemodynamically relevant non-IRA lesions with higher accuracy than FFRi measured at the index PCI, using follow-up FFRi as the reference standard. Early FFRCT in STEMI patients might represent a new application for cardiac CT to improve the identification of patients who benefit most from staged non-IRA revascularization.

The Predictive Value of Left Atrial Strain Following Transcatheter Aortic Valve Implantation on Anatomical and Functional Reverse Remodeling in a Multi-Modality Study.

Introduction: Transcatheter aortic valve implantation (TAVI) can improve left ventricular (LV) mechanics and survival. Data on the predictive value of left atrial (LA) strain following TAVI are scarce. We aimed to evaluate the association of LA strain measured shortly post-TAVI with functional and anatomical reverse remodeling of the LA and LV, and its association with mortality. Methods: We prospectively investigated 90 patients who underwent TAVI. Transthoracic echocardiography including strain analysis was performed shortly after TAVI and repeated 6 months later. CT angiography (CTA) was performed for pre-TAVI planning and 6 months post-TAVI. Speckle tracking echocardiography was used to determine LA peak reservoir strain (LASr) and LV global longitudinal strain (LV-GL), LA volume index (LAVi) was measured by TTE. LV mass index (LVMi) was calculated using CTA images. LA reverse remodeling was based on LASr and LAVi changes, whereas LV reverse remodeling was defined as an improvement in LV-GLS or a reduction of LVMi. The association of severely reduced LASr (<20%) at baseline with changes (Δ) in LASr, LAVi, LV-GLS and LVMi were analyzed using linear regression, and Cox proportional hazard model for mortality. Results: Mean LASr and LV-GLS were 17.7 ± 8.4 and -15.3 ± 3.4% at baseline and 20.2 ± 10.2 and -16.6 ± 4.0% at follow-up (p = 0.024 and p < 0.001, respectively). Severely reduced LASr at baseline was associated with more pronounced ΔLASr (ß = 5.24, p = 0.025) and LVMi reduction on follow-up (ß = 5.78, p = 0.036), however, the majority of the patients had <20% LASr on follow-up (44.4%). Also, ΔLASr was associated with ΔLV-GLS (adjusted ß = 2.10, p < 0.001). No significant difference in survival was found between patients with baseline severely reduced LASr (<20%) and higher LASr (≥20%) (p = 0.054). Conclusion: LV reverse remodeling based on LVMi was present even in patients with severely reduced LASr following TAVI, although extensive LA damage based on LA strain was demonstrated by its limited improvement over time. Clinical Trial Registration: (ClinicalTrials.gov number: NCT02826200).

Heritability of Coronary Artery Disease: Insights From a Classical Twin Study.

BACKGROUND: Genetics have a strong influence on calcified atherosclerotic plaques; however, data regarding the heritability of noncalcified plaque volume are scarce. We aimed to evaluate genetic versus environmental influences on calcium (coronary artery calcification) score, noncalcified and calcified plaque volumes by coronary computed tomography angiography in adult twin pairs without known coronary artery disease. METHODS: In the prospective BUDAPEST-GLOBAL (Burden of Atherosclerotic Plaques Study in Twins-Genetic Loci and the Burden of Atherosclerotic Lesions) classical twin study, we analyzed twin pairs without known coronary artery disease. All twins underwent coronary computed tomography angiography to assess coronary atherosclerotic plaque volumes. Structural equation models were used to quantify the contribution of additive genetic, common environmental, and unique environmental components to plaque volumes adjusted for age, gender, or atherosclerotic cardiovascular disease risk estimate and statin use. RESULTS: We included 196 twins (mean age±SD, 56±9 years, 63.3% females), 120 monozygotic and 76 same-gender dizygotic pairs. Using structural equation models, noncalcified plaque volume was predominantly determined by environmental factors (common environment, 63% [95% CI, 56%-67%], unique environment, 37% [95% CI, 33%-44%]), while coronary artery calcification score and calcified plaque volumes had a relatively strong genetic heritability (additive genetic, 58% [95% CI, 50%-66%]; unique environmental, 42% [95% CI, 34%-50%] and additive genetic, 78% [95% CI, 73%-80%]; unique environmental, 22% [95% CI, 20%-27%]), respectively. CONCLUSIONS: Noncalcified plaque volume is mainly influenced by shared environmental factors, whereas coronary artery calcification score and calcified plaque volume are more determined by genetics. These findings emphasize the importance of early lifestyle interventions in preventing coronary plaque formation. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01738828.

Predictors and neurological consequences of periprocedural cerebrovascular events following transcatheter aortic valve implantation with self-expanding valves.

Aims: To evaluate the patient- and procedure-related predictors of transcatheter aortic-valve implantation (TAVI)-associated ischemic brain lesions and to assess the effect of silent cerebral ischemic lesions (SCIL) on neurocognitive function. Methods and results: We investigated 113 consecutive patients with severe aortic stenosis who underwent brain magnetic resonance imaging (MRI) within a week following TAVI. To assess periprocedural cerebral ischemic lesions, diffusion-weighted MRI was utilized. We used multivariate linear regression to identify the independent predictors of TAVI-related ischemic lesion volume (ILV) and periprocedural stroke. Neurocognitive evaluation was performed before and following TAVI at 6-month and one-year follow-up. Following TAVI, a total of 944 new cerebral ischemic lesions were detected in 104 patients (92%). The median ILV was 257 µl (interquartile range [IQR]:97.1-718.8µl) with a median lesion number of 6/patient [IQR:2-10]. The majority of ischemic lesions were clinically silent (95%), while 5% of the lesions induced a stroke, which was confirmed by MRI. Predilatation (ß = 1.13[95%CI:0.32-1.93], p = 0.01) and the number of valve positioning attempts during implantation (ß = 0.28[95%CI:0.06-0.50], p = 0.02) increased the log-transformed total ILV. Predilatation (OR = 12.04[95%CI:1.46-99.07], p = 0.02) and alternative access routes (OR = 7.84[95%CI:1.01-61.07], p = 0.02) were associated with stroke after adjustments for comorbidities and periprocedural factors. The presence of SCILs were not associated with a change in neurocognitive function that remained stable during the one-year follow-up. Conclusion: While periprocedural ischemic lesions are frequent, most of them are clinically silent and might not impact the patients' neurocognitive function. The number of valve positioning attempts, predilatation, and alternative access routes should be taken into consideration during TAVI to reduce the ILV and risk for stroke.

Association between coronary plaque volume and myocardial ischemia detected by dynamic perfusion CT imaging.

Introduction: We aimed to evaluate the relationship between quantitative plaque metrics derived from coronary CT angiography (CTA) and segmental myocardial ischemia using dynamic perfusion CT (DPCT). Methods: In a prospective single-center study, patients with > 30% stenosis on rest CTA underwent regadenoson stress DPCT. 480 myocardium segments of 30 patients were analyzed. Quantitative plaque assessment included total plaque volume (PV), area stenosis, and remodeling index (RI). High-risk plaque (HRP) was defined as low-attenuation plaque burden > 4% or RI > 1.1. Absolute myocardial blood flow (MBF) and relative MBF (MBFi: MBF/75th percentile of all MBF values) were quantified. Linear and logistic mixed models correcting for intra-patient clustering and clinical factors were used to evaluate the association between total PV, area stenosis, HRP and MBF or myocardial ischemia (MBF < 101 ml/100 g/min). Results: Median MBF and MBFi were 111 ml/100 g/min and 0.94, respectively. The number of ischemic segments were 164/480 (34.2%). Total PV of all feeding vessels of a given myocardial territory differed significantly between ischemic and non-ischemic myocardial segments (p = 0.001). Area stenosis and HRP features were not linked to MBF or MBFi (all p > 0.05). Increase in PV led to reduced MBF and MBFi after adjusting for risk factors including hypertension, diabetes, and statin use (per 10 mm3; ß = -0.035, p < 0.01 for MBF; ß = -0.0002, p < 0.01 for MBFi). Similarly, using multivariate logistic regression total PV was associated with ischemia (OR = 1.01, p = 0.033; per 10 mm3) after adjustments for clinical risk factors, area stenosis and HRP. Conclusion: Total PV was independently associated with myocardial ischemia based on MBF, while area stenosis and HRP were not.

Subclinical leaflet thrombosis after transcatheter aortic valve implantation is associated with silent brain injury on brain magnetic resonance imaging.

AIMS: Whether hypoattenuated leaflet thickening (HALT) following transcatheter aortic valve implantation (TAVI) carries a risk of subclinical brain injury (SBI) is unknown. We investigated whether HALT is associated with SBI detected on magnetic resonance imaging (MRI), and whether post-TAVI SBI impacts the patients' cognition and outcome. METHODS AND RESULTS: We prospectively enrolled 153 patients (age: 78.1 ± 6.3 years; female 44%) who underwent TAVI. Brain MRI was performed shortly post-TAVI and 6 months later to assess the occurrence of acute silent cerebral ischaemic lesions (SCIL) and chronic white matter hyperintensities (WMH). HALT was screened by cardiac computed tomography (CT) angiography (CTA) 6 months post-TAVI. Neurocognitive evaluation was performed before, shortly after and 6 months following TAVI. At 6 months, 115 patients had diagnostic CTA and 10 had HALT. HALT status, baseline, and follow-up MRIs were available in 91 cases. At 6 months, new SCIL was evident in 16%, new WMH in 66%. New WMH was more frequent (100 vs. 62%; P = 0.047) with higher median volume (319 vs. 50 mm3; P = 0.039) among HALT-patients. In uni- and multivariate analysis, HALT was associated with new WMH volume (beta: 0.72; 95%CI: 0.2-1.39; P = 0.009). The patients' cognitive trajectory from pre-TAVI to 6 months showed significant association with the 6-month SCIL volume (beta: -4.69; 95%CI: -9.13 to 0.27; P = 0.038), but was not related to the presence or volume of new WMH. During a 3.1-year follow-up, neither HALT [hazard ratio (HR): 0.86; 95%CI: 0.202-3.687; P = 0.84], nor the related WMH burden (HR: 1.09; 95%CI: 0.701-1.680; P = 0.71) was related with increased mortality. CONCLUSIONS: At 6 months post-TAVI, HALT was linked with greater WMH burden, but did not carry an increased risk of cognitive decline or mortality over a 3.1-year follow-up (NCT02826200).

Effect of genetic and environmental influences on cardiometabolic risk factors: a twin study.

BACKGROUND: Both genetic and environmental factors play a role in the pathogenesis of type 2 diabetes and cardiovascular diseases. The magnitude of genetic and environmental influences may vary in different populations and can be investigated by twin studies. METHODS: In this cross-sectional study, 101 (63 monozygotic and 38 dizygotic) adult twin pairs (n = 202; mean age: 44.3 ± 15.8 years) were investigated. Past medical history was recorded and physical examination was performed. Fasting venous blood samples were taken for measuring laboratory parameters. For assessing heritability of 14 cardiovascular risk factors, the structural equation (A-C-E) model was used. RESULTS: The following risk factors were highly (> 70.0%) or moderately (50.0 - 69.0%) heritable: weight (88.1%), waist circumference (71.0%), systolic blood pressure (57.1%), diastolic blood pressure (57.7%), serum creatinine (64.1%), fibrinogen (59.9%), and serum C-reactive protein (51.9%). On the other hand, shared and unique environmental influences had the highest proportion of total phenotypic variance in serum total cholesterol (46.8% and 53.2%), serum HDL-cholesterol (58.1% and 14.9%), triglycerides (0.0% and 55.9%), fasting blood glucose (57.1% and 42.9%), fasting insulin (45.4% and 54.5%), serum uric acid (46.0% and 31.3%), and serum homocysteine (71.8% and 28.2%, respectively). CONCLUSION: Some cardiometabolic risk factors have strong heritability while others are substantially influenced by environmental factors. Understanding the special heritability characteristics of a particular risk factor can substantiate further investigations, especially in molecular genetics. Moreover, identifying genetic and environmental contribution to certain cardiometabolic risk factors can help in designing prevention and treatment strategies in the population investigated.

Genetic and environmental factors on heart rate, mean arterial pressure and carotid intima-media thickness: A longitudinal twin study.

BACKGROUND: Heart rate (HR), mean arterial pressure (MAP) and carotid intima-media thickness (cIMT) are moderately heritable cardiovascular traits, but the environmental effects on the longitudinal change of their heritability have never been investigated. METHODS: 368 Italian and Hungarian twins (107 monozygotic, 77 dizygotic) underwent oscillometric measurement and B-mode sonography of bilateral carotid arteries in 2009/2010 and 2014. Within- -individual/cross-study wave, cross-twin/within-study wave and cross-twin/cross-study wave correlations were estimated, and bivariate Cholesky models were fitted to decompose the total variance at each wave and covariance between study waves into additive genetic, shared and unique environmental components. RESULTS: For each trait, a moderate longitudinal stability was observed, with within-individual/crosswave correlations of 0.42 (95% CI: 0.33-0.51) for HR, 0.34 (95% CI: 0.24-0.43) for MAP, and 0.23 (95% CI: 0.12-0.33) for cIMT. Cross-twin/cross-wave correlations in monozygotic pairs were all significant and substantially higher than the corresponding dizygotic correlations. Genetic continuity was the main source of longitudinal stability, with across-time genetic correlations of 0.52 (95% CI: 0.29-0.71) for HR, 0.56 (95% CI: 0.31-0.81) for MAP, and 0.36 (95% CI: 0.07-0.64) for cIMT. Overlapping genetic factors explained respectively 57%, 77%, and 68% of the longitudinal covariance of the HR, MAP and cIMT traits. CONCLUSIONS: Genetic factors have a substantial role in the longitudinal change of HR, MAP and cIMT; however, the influence of unique environmental factors remains relevant. Further studies should better elucidate whether epigenetic mechanisms have a role in influencing the stability of the investigated traits over time.

Environmental Factors Slightly Outweigh Genetic Influences in the Development of Pancreatic Lipid Accumulation: A Classical Twin Study.

Background: Several studies showed that lipid accumulation in the pancreas (NAFPD: nonalcoholic fatty pancreas disease) may lead to different pancreatic disorders, including beta-cell dysfunction. The role of genetic and environmental factors in pancreatic lipid accumulation is unclear. We evaluated the magnitude of genetic and environmental impact on pancreatic lipid content within a cohort of adult twin pairs. Patients and Methods: We investigated 136 twin subjects [monozygotic (MZ, n = 86) and dizygotic (DZ, n = 50) same-gender twins (age 57.7 ± 9.1 years; body mass index [BMI] 28.0 ± 4.4 kg/m2; females 64.7%)] with a 256-slice computed tomography (CT)-scanner. Using nonenhanced CT images, we calculated the average value of pancreatic attenuation expressed in Hounsfield unit (HU) suggesting pancreatic lipid content. Crude data were adjusted to age, sex, BMI, and hemoglobinA1c values. Intrapair correlations were established, and structural equation models were used for quantifying the contribution of additive genetic (A), common environmental (C), and unique environmental (E) components to the investigated phenotype. Results: The study cohort represented a moderately overweight, middle-aged Caucasian population. Average pancreatic attenuation was 48.9 ± 11.9 HU in MZ and 49.0 ± 13.0 HU in DZ twins (P = 0.934). The intrapair correlation between HU values was stronger in MZ compared to DZ twins (rMZ = 0.536, P < 0.001; rDZ = 0.115, P = 0.580). Using the structural equation model, a greater unique environmental influence [E: 54%, 95% confidence interval (CI) 19%-66%] and a moderate additive genetic dependence (A: 46%, 95% CI 34%-81%) were found. Conclusions: The results of our classical twin study indicate that environmental (lifestyle) influences slightly outweigh genetic effects on the phenotypic appearance of pancreatic lipid accumulation known as NAFPD.

Quantification of hypo-attenuated leaflet thickening after transcatheter aortic valve implantation: clinical relevance of hypo-attenuated leaflet thickening volume.

AIMS: Our aim was to establish an objective, quantitative methodology for volumetric hypo-attenuated leaflet thickening (HALT) diagnosis and evaluate its clinical significance. METHODS AND RESULTS: We prospectively enrolled 144 patients who underwent transcatheter aortic valve implantation (TAVI) between 2011 and 2016. At inclusion, cardiac computed tomography angiography (CTA), transthoracic echocardiography, and brain magnetic resonance imaging (MRI) were performed. We quantified HALT on CTA datasets by segmenting the inner volume of TAVI frame at the level of leaflets and extracted voxels between a threshold of -200 to 200 HU based on prior recommendation. The median HALT volume was 72 [inter-quartile range (IQR): 1-154] mm3 (intra- and inter-reader agreement: intra-class correlation coefficient = 0.92 and 0.94, respectively) and 79% (n = 87/111) of the patients had HALT >0 mm3. In multivariate linear regression, oral anti-coagulation (ß: -0.32; 95% CI: -0.62 to -0.01; P = 0.004) and history of myocardial infarction (ß: 0.32; 95% CI: 0.01-0.63; P = 0.043) were associated with HALT quantity. Log-transformed HALT volume was associated with elevated (>13 mmHg) aortic mean gradient (AMG, OR: 12.85; 95% CI: 1.96-152.93; P = 0.021) and moderate-to-severe valvular degeneration (AMG ≥ 20 mmHg or ΔAMG ≥ 10 mmHg; OR: 10.56; 95% CI: 1.44-148.71; P = 0.046) but did not predict ischaemic brain lesions on MRI or all-cause death after a median follow-up of 29 (IQR: 11-29) months (all P > 0.05). CONCLUSION: Through systematic analysis of asymptomatic patients with TAVI, an objective and reproducible methodology was feasible for volumetric measurement of HALT. Anti-coagulation might have a protective effect against HALT. Ischaemic brain lesions and all-cause death were not associated with HALT; nevertheless, it might deteriorate prosthesis function due to its association with elevated AMG. CLINICAL TRIAL REGISTRATION: http//:www.ClinicalTrials.gov; NCT02826200.

Subclinical leaflet thrombosis is associated with impaired reverse remodelling after transcatheter aortic valve implantation.

AIMS: Cardiac CT is increasingly applied for planning and follow-up of transcatheter aortic valve implantation (TAVI). However, there are no data available on reverse remodelling after TAVI assessed by CT. Therefore, we aimed to evaluate the predictors and the prognostic value of left ventricular (LV) reverse remodelling following TAVI using CT angiography. METHODS AND RESULTS: We investigated 117 patients with severe, symptomatic aortic stenosis (AS) who underwent CT scanning before and after TAVI procedure with a mean follow-up time of 2.6 years after TAVI. We found a significant reduction in LV mass (LVM) and LVM indexed to body surface area comparing pre- vs. post-TAVI images: 180.5 ± 53.0 vs. 137.1 ± 44.8 g and 99.7 ± 25.4 vs. 75.4 ± 19.9 g/m2, respectively, both P < 0.001. Subclinical leaflet thrombosis (SLT) was detected in 25.6% (30/117) patients. More than 20% reduction in LVM was defined as reverse remodelling and was detected in 62.4% (73/117) of the patients. SLT, change in mean pressure gradient on echocardiography and prior myocardial infarction was independently associated with LV reverse remodelling after adjusting for age, gender, and traditional risk factors (hypertension, body mass index, diabetes mellitus, and hyperlipidaemia): OR = 0.27, P = 0.022 for SLT and OR = 0.22, P = 0.006 for prior myocardial infarction, OR = 1.51, P = 0.004 for 10 mmHg change in mean pressure gradient. Reverse remodelling was independently associated with favourable outcomes (HR = 0.23; P = 0.019). CONCLUSION: TAVI resulted in a significant LVM regression on CT. The presence of SLT showed an inverse association with LV reverse remodelling and thus it may hinder the beneficial LV structural changes. Reverse remodelling was associated with improved long-term prognosis.

Genetic and environmental determinants of longitudinal stability of arterial stiffness and wave reflection: a twin study.

BACKGROUND: We aimed at evaluating the impact of genetic and environmental factors on longitudinal changes in aortic pulse wave velocity (aPWV) and aortic augmentation index (aAIx). METHOD: Three hundred and sixty-eight Italian and Hungarian adult twins (214 monozygotic, 154 dizygotic) underwent repeated evaluations of aPWV and aAIx (TensioMed Arteriograph). Within-individual/cross-wave, cross-twin/within-wave and cross-twin/cross-wave correlations were calculated; bivariate Cholesky models were fitted to calculate additive genetic (A), shared environmental (C) and unique environmental (E) components. RESULTS: For both aPWV and aAIx, cross-twin correlations in monozygotic pairs (r between 0.35 and 0.56) were all significant and always higher than in dizygotic pairs, both at wave 1 and at wave 2. Heritability and unshared environmental proportion of variance at each wave were substantially time-invariant for aPWV (heritability 0.51, 95% CI 0.36-0.63 at wave 1; 0.49, 95% CI 0.34-0.62 at wave 2), whereas for aAIx, we observed a diminished genetic effect (heritability 0.57, 95% CI 0.45-0.67 at wave 1; 0.37, 95% CI 0.21-0.51 at wave 2). Overlapping genetic factors explained a high proportion (0.88, 95% CI 0.61-1.00) of longitudinal covariance for aPWV, and had a relatively lower impact on aAIx (0.55, 95% CI 0.35-0.70). Genetic correlations of aPWV (r = 0.64, 95% CI 0.42-0.85) and aAIx (r = 0.70, 95% CI 0.52-0.87) between waves were lower than 1, suggesting a potential contribution of novel genetic variance on arterial stiffening. CONCLUSION: Changes in aPWV and aAIx over time are largely genetically determined. Our results might stimulate further studies on genetic and epigenetic factors influencing the process of vascular ageing.