This thesis investigated how coronary CT, a non-invasive imaging technique, can be used in clinical practice to better characterize coronary artery calcification and to improve risk stratification.... Show moreThis thesis investigated how coronary CT, a non-invasive imaging technique, can be used in clinical practice to better characterize coronary artery calcification and to improve risk stratification. We looked at sex-differences in the development of atherosclerosis and the differences in risks of a possible event. Development of atherosclerosis started 12 years later in women, but when both sexes have severe arteriosclerosis, women have a higher chance of an event (myocardial infarction and/or death). Furthermore, with serial coronary CT scans and detailed quantification of atherosclerosis, we analyzed which patients are more likely to have progression of atherosclerosis, despite the use of a statin (cholesterol lowering agent). Growth of plaque is associated with worse outcomes and these patients might benefit from a different and/or more aggressive treatment. Furthermore, measurement of the pericoronary adipose tissue has been postulated as a new biomarker to detect inflammation of the coronary arteries, which plays an important role in the formation and progression of atherosclerosis, and in this thesis we have attempted to establish reference values. Show less
Martens, L.G.; Hamersveld, D. van; Cessie, S. le; Dijk, K.W. van; Heemst, D. van; Noordam, R. 2023
Objectives: Low socioeconomic status (SES) is associated with cardiovascular risk factors and increased coronary artery disease (CAD) risk. We tested whether SES is an effect modifier of the... Show moreObjectives: Low socioeconomic status (SES) is associated with cardiovascular risk factors and increased coronary artery disease (CAD) risk. We tested whether SES is an effect modifier of the association between classical cardiovascular risk factors and CAD using SES-stratified Mendelian Randomization in European-ancestry participants from UK Biobank.Study Design and Setting: We calculated weighted genetic risk scores (GRS) for the risk factors body mass index (BMI), systolic blood pressure, low-density lipoprotein cholesterol, and triglycerides. Participants were stratified by Townsend deprivation index score. Lo-gistic regression models were used to investigate associations between GRSs and CAD occurrence. Additionally, stratification based on GRS-adjusted Townsend deprivation index residuals was conducted to correct for possible collider-stratification bias.Results: In a total sample size of N 5 446,485, with 52,946 cases, the risk for CAD per standard deviation increase in genetically influenced BMI was highest in the group with the lowest 25% SES (odds ratio: 1.126, 95% confidence interval: 1.106-1.145; odds ratio: 1.081, 95% confidence interval: 1.059-1.103 in high SES), remaining similar after controlling for possible collider-stratification bias. The effects of genetically influenced systolic blood pressure, low-density lipoprotein cholesterol, and triglyceride on CAD were similar between SES groups.Conclusion: CAD risk attributable to increased BMI is not homogenous and could be modified by SES. This emphasizes the need of tailor-made approaches for BMI-associated CAD risk reduction. & COPY; 2023 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Show less
Aims Lowering low-density lipoprotein (LDL-C) and blood pressure (BP) levels to guideline recommended values reduces the risk of major adverse cardiac events in patients who underwent coronary... Show moreAims Lowering low-density lipoprotein (LDL-C) and blood pressure (BP) levels to guideline recommended values reduces the risk of major adverse cardiac events in patients who underwent coronary artery bypass grafting (CABG). To improve cardiovascular risk management, this study evaluated the effects of mobile health (mHealth) on BP and cholesterol levels in patients after standalone CABG.Methods and results This study is a post hoc analysis of an observational cohort study among 228 adult patients who underwent standalone CABG surgery at a tertiary care hospital in The Netherlands. A total of 117 patients received standard care, and 111 patients underwent an mHealth intervention. This consisted of frequent BP and weight monitoring with regimen adjustment in case of high BP. Primary outcome was difference in systolic BP and LDL-C between baseline and value after three months of follow-up. Mean age in the intervention group was 62.7 years, 98 (88.3%) patients were male. A total of 26 449 mHealth measurements were recorded. At three months, systolic BP decreased by 7.0 mmHg [standard deviation (SD): 15.1] in the intervention group vs. -0.3 mmHg (SD: 17.6; P < 0.00001) in controls; body weight decreased by 1.76 kg (SD: 3.23) in the intervention group vs. -0.31 kg (SD: 2.55; P = 0.002) in controls. Serum LDL-C was significantly lower in the intervention group vs. controls (median: 1.8 vs. 2.0 mmol/L; P = 0.0002).Conclusion This study showed an association between home monitoring after CABG and a reduction in systolic BP, body weight, and serum LDL-C. The causality of the association between the observed weight loss and decreased LDL-C in intervention group patients remains to be investigated. Show less
IntroductionBicuspid aortic valve (BAV) patients have an increased risk to develop thoracic aortic complications. Little is known about the prevalence and severity of atherosclerosis in the BAV... Show moreIntroductionBicuspid aortic valve (BAV) patients have an increased risk to develop thoracic aortic complications. Little is known about the prevalence and severity of atherosclerosis in the BAV ascending aortic wall. This study evaluates and compares the prevalence of thoracic aortic atherosclerosis in BAV and tricuspid aortic valve (TAV) patients.MethodsAtherosclerosis was objectified using three diagnostic modalities in two separate BAV patient cohorts (with and without an aortic dilatation). Within the first group, atherosclerosis was graded histopathologically according to the modified AHA classification scheme proposed by Virmani et al. In the second group, the calcific load of the ascending aorta and coronary arteries, coronary angiographies and cardiovascular risk factors were studied. Patients were selected from a surgical database (treated between 2006-2020), resulting in a total of 128 inclusions.ResultsHistopathology showed atherosclerotic lesions to be more prevalent and severe in all TAV as compared to all BAV patients (OR 1.49 (95%CI 1.14 - 1.94); p = 0.003). Computed tomography showed no significant differences in ascending aortic wall calcification between all BAV and all TAV patients, although a tendency of lower calcific load in favor of BAV was seen. Coronary calcification was higher in all TAV as compared to all BAV (OR 1.30 (95%CI 1.06 - 1.61); p = 0.014).ConclusionAscending aortic atherosclerotic plaques were histologically more pronounced in TAV as compared to the BAV patients, while CT scans revealed equal amounts of calcific depositions within the ascending aortic wall. This study confirms less atherosclerosis in the ascending aortic wall and coronary arteries of BAV patients as compared to TAV patients. These results were not affected by the presence of a thoracic aortic aneurysm. Show less
Bulk, S. van den; Spoelman, W.A.; Dijkman, P.R.M. van; Numans, M.E.; Bonten, T.N.; Leiden Univ Med Ctr LUMC 2022
Background: The prevalence of coronary artery disease is increasing due to the aging population and increasing prevalence of cardiovascular risk factors. Non-acute chest pain often is the first... Show moreBackground: The prevalence of coronary artery disease is increasing due to the aging population and increasing prevalence of cardiovascular risk factors. Non-acute chest pain often is the first symptom of stable coronary artery disease. To optimise care for patients with non-acute chest pain and make efficient use of available resources, we need to know more about the current incidence, referral rate and management of these patients. Methods: We used routinely collected health data from the STIZON data warehouse in the Netherlands between 2010 and 2016. Patients > 18 years, with no history of cardiovascular disease, seen by the general practitioner (GP) for non-acute chest pain with a suspected cardiac origin were included. Outcomes were (i) incidence of new non-acute chest pain in primary care, (ii) referral rates to the cardiologist, (iii) correspondence from the cardiologist to the GP, (iv) registration by GPs of received correspondence and; (v) pharmacological guideline adherence after newly diagnosed stable angina pectoris. Results: In total 9029 patients were included during the study period, resulting in an incidence of new non-acute chest pain of 1.01/1000 patient-years. 2166 (24%) patients were referred to the cardiologist. In 857/2114 (41%) referred patients, correspondence from the cardiologist was not available in the GP's electronic medical record. In 753/1257 (60%) patients with available correspondence, the GP did not code the conclusion in the electronic medical record. Despite guideline recommendations, 37/255 (15%) patients with angina pectoris were not prescribed antiplatelet therapy nor anticoagulation, 69/255 (27%) no statin and 67/255 (26%) no beta-blocker. Conclusion: After referral, both communication from cardiologists and registration of the final diagnosis by GPs were suboptimal. Both cardiologists and GPs should make adequate communication and registration a priority, as it improves health outcomes. Secondary pharmacological prevention in patients with angina pectoris was below guideline standards. So, proactive attention needs to be given to optimise secondary prevention in this high-risk group in primary care. Show less
Luo, J.; Noordam, R.; Jukema, J.W.; Dijk, K.W. van; Hagg, S.; Grassmann, F.; ... ; Heemst, D. van 2022
Aim: Mitochondrial DNA dysfunction has been implicated in the pathogenesis of cardiovascular diseases. We aimed to investigate the associations between leukocyte mitochondrial DNA (mtDNA) abundance... Show moreAim: Mitochondrial DNA dysfunction has been implicated in the pathogenesis of cardiovascular diseases. We aimed to investigate the associations between leukocyte mitochondrial DNA (mtDNA) abundance, as a proxy of mitochondrial function, and coronary artery disease (CAD) and heart failure (HF) in a cohort study and approximate the causal nature of these relationships using Mendelian randomization (MR) in genetic studies. Methods and results: Multivariable-adjusted Cox regression analyses were conducted in 273 619 unrelated participants of European ancestry from the UK Biobank (UKB). For genetic studies, we first performed MR analyses with individual-level data from the UKB using a weighted genetic risk score (GRS); two-sample MR analyses were subsequently performed using summary-level data from the publicly available three consortia/biobank for CAD and two for HF. MR analyses were performed per database separately and results were subsequently meta-analysed using fixed-effects models. During a median follow-up of 11.8 years, restricted cubic spline Cox regression analyses showed associations between lower mtDNA abundance and higher risk of CAD and HF. Hazard ratios for participants in the lowest quintile of mtDNA abundance compared with those in the highest quintile were 1.08 (95% confidence interval: 1.03, 1.14) and 1.15 (1.05, 1.24) for CAD and HF. Genetically, no evidence was observed for a possible non-linear causal effect using individual-level weighted genetic risk scores calculated in the UKB on the study outcomes; the pooled odds ratios (95% confidence interval) from two-sample MR of genetically predicted per one-SD decrease in mtDNA abundance were 1.09 (1.03, 1.16) for CAD and 0.99 (0.92, 1.08) for HF, respectively. Conclusion: Our findings support a possible causal role of lower leukocyte mtDNA abundance in higher CAD risk, but not in HF. Show less
Luo, J.; Noordam, R.; Jukema, J.W.; Dijk, K.W. van; Hägg, S.; Grassmann, F.; ... ; Heemst, D. van 2022
AimMitochondrial DNA dysfunction has been implicated in the pathogenesis of cardiovascular diseases. We aimed to investigate the associations between leukocyte mitochondrial DNA (mtDNA) abundance,... Show moreAimMitochondrial DNA dysfunction has been implicated in the pathogenesis of cardiovascular diseases. We aimed to investigate the associations between leukocyte mitochondrial DNA (mtDNA) abundance, as a proxy of mitochondrial function, and coronary artery disease (CAD) and heart failure (HF) in a cohort study and approximate the causal nature of these relationships using Mendelian randomization (MR) in genetic studies.Methods and resultsMultivariable-adjusted Cox regression analyses were conducted in 273 619 unrelated participants of European ancestry from the UK Biobank (UKB). For genetic studies, we first performed MR analyses with individual-level data from the UKB using a weighted genetic risk score (GRS); two-sample MR analyses were subsequently performed using summary-level data from the publicly available three consortia/biobank for CAD and two for HF. MR analyses were performed per database separately and results were subsequently meta-analysed using fixed-effects models. During a median follow-up of 11.8 years, restricted cubic spline Cox regression analyses showed associations between lower mtDNA abundance and higher risk of CAD and HF. Hazard ratios for participants in the lowest quintile of mtDNA abundance compared with those in the highest quintile were 1.08 (95% confidence interval: 1.03, 1.14) and 1.15 (1.05, 1.24) for CAD and HF. Genetically, no evidence was observed for a possible non-linear causal effect using individual-level weighted genetic risk scores calculated in the UKB on the study outcomes; the pooled odds ratios (95% confidence interval) from two-sample MR of genetically predicted per one-SD decrease in mtDNA abundance were 1.09 (1.03, 1.16) for CAD and 0.99 (0.92, 1.08) for HF, respectively.ConclusionOur findings support a possible causal role of lower leukocyte mtDNA abundance in higher CAD risk, but not in HF. Show less
Background: Additional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models... Show moreBackground: Additional strategies are needed to refine the referral for diagnostic testing of symptomatic patients with suspected coronary artery disease (CAD). We aimed to compare various models to predict hemodynamically obstructive CAD. Methods and results: Symptomatic patients with suspected CAD who underwent coronary artery calcium scoring (CACS) and sequential coronary computed tomography angiography (CCTA) and [O-15]H2O positron emission tomography (PET) myocardial perfusion imaging were analyzed. Obstructive CAD was defined as a suspected coronary artery stenosis on CCTA with myocardial ischemia on PET (absolute stress myocardial perfusion <= 2.4 mL/g/min in >= 1 segment). Three models were developed to predict obstructive CAD-induced myocardial ischemia using logistic regression analysis: (1) basic model: including age, sex and cardiac symptoms, (2) risk factor model: adding number of risk factors to the basic model, and (3) CACS model: adding CACS to the risk factor model. Model performance was evaluated using discriminatory ability with area under the receiver-operating characteristic curves (AUC). A total of 647 patients (mean age 62 +/- 9 years, 45% men) underwent CACS and sequential CCTA and PET myocardial perfusion imaging. Obstructive CAD with myocardial ischemia on PET was present in 151 (23%) patients. CACS was independently associated with myocardial ischemia (P < .001). AUC for the discrimination of ischemia for the CACS model was superior over the basic model and risk factor model (P < .001). Conclusions: Adding CACS to the model including age, sex, cardiac symptoms and number of risk factors increases the accuracy to predict obstructive CAD with myocardial ischemia on PET in symptomatic patients with suspected CAD. Show less
Albalak, G.; Stijntjes, M.; Bodegom, D. van; Jukema, J.W.; Atsma, D.E.; Heemst, D. van; Noordam, R. 2022
Aims Little is known about the impact of daily physical activity timing (here referred to as 'chronoactivity') on cardiovascular disease (CVD) risk. We aimed to examined the associations between... Show moreAims Little is known about the impact of daily physical activity timing (here referred to as 'chronoactivity') on cardiovascular disease (CVD) risk. We aimed to examined the associations between chronoactivity and multiple CVD outcomes in the UK Biobank. Methods and results physical activity data were collected in the UK-Biobank through triaxial accelerometer over a 7-day measurement period. We used K-means clustering to create clusters of participants with similar chronoactivity irrespective of the mean daily intensity of the physical activity. Multivariable-adjusted Cox-proportional hazard models were used to estimate hazard ratios (HRs) comparing the different clusters adjusted for age and sex (model 1), and baseline cardiovascular risk factors (model 2). Additional stratified analyses were done by sex, mean activity level, and self-reported sleep chronotype. We included 86 657 individuals (58% female, mean age: 61.6 [SD: 7.8] years, mean BMI: 26.6 [4.5] kg/m(2)). Over a follow-up period of 6 years, 3707 incident CVD events were reported. Overall, participants with a tendency of late morning physical activity had a lower risk of incident coronary artery disease (HR: 0.84, 95%CI: 0.77, 0.92) and stroke (HR: 0.83, 95%CI: 0.70, 0.98) compared to participants with a midday pattern of physical activity. These effects were more pronounced in women (P-value for interaction = 0.001). We did not find evidence favouring effect modification by total activity level and sleep chronotype. Conclusion Irrespective of total physical activity, morning physical activity was associated with lower risks of incident cardiovascular diseases, highlighting the potential importance of chronoactivity in CVD prevention. Show less
Won, K.B.; Lee, B.K.; Lin, F.Y.; Hadamitzky, M.; Kim, Y.J.; Sung, J.M.; ... ; Chang, H.J. 2022
Background: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the... Show moreBackground: The baseline coronary plaque burden is the most important factor for rapid plaque progression (RPP) in the coronary artery. However, data on the independent predictors of RPP in the absence of a baseline coronary plaque burden are limited. Thus, this study aimed to investigate the predictors for RPP in patients without coronary plaques on baseline coronary computed tomography angiography (CCTA) images. Methods: A total of 402 patients (mean age: 57.6 +/- 10.0 years, 49.3% men) without coronary plaques at baseline who underwent serial coronary CCTA were identified from the Progression of Atherosclerotic Plaque Determined by Computed Tomographic Angiography Imaging (PARADIGM) registry and included in this retrospective study. RPP was defined as an annual change of >= 1.0%/year in the percentage atheroma volume (PAV). Results: During a median inter-scan period of 3.6 years (interquartile range: 2.7-5.0 years), newly developed coronary plaques and RPP were observed in 35.6% and 4.2% of the patients, respectively. The baseline traditional risk factors, i.e., advanced age (>= 60 years), male sex, hypertension, diabetes mellitus, hyperlipidemia, obesity, and current smoking status, were not significantly associated with the risk of RPP. Multivariate linear regression analysis showed that the serum hemoglobin A1c level (per 1% increase) measured at follow-up CCTA was independently associated with the annual change in the PAV (beta: 0.098, 95% confidence interval [CI]: 0.048-0.149; P < 0.001). The multiple logistic regression models showed that the serum hemoglobin A1c level had an independent and positive association with the risk of RPP. The optimal predictive cut-off value of the hemoglobin A1c level for RPP was 7.05% (sensitivity: 80.0%, specificity: 86.7%; area under curve: 0.816 [95% CI: 0.574-0.999]; P = 0.017). Conclusion: In this retrospective case-control study, the glycemic control status was strongly associated with the risk of RPP in patients without a baseline coronary plaque burden. This suggests that regular monitoring of the glycemic control status might be helpful for preventing the rapid progression of coronary atherosclerosis irrespective of the baseline risk factors. Further randomized investigations are necessary to confirm the results of our study. Show less
Schultz, J.; Hoogen, I.J. van den; Kuneman, J.H.; Graaf, M.A. de; Kamperidis, V.; Broersen, A.; ... ; Knuuti, J. 2022
Endothelial wall shear stress (ESS) is a biomechanical force which plays a role in the formation and evolution of atherosclerotic lesions. The purpose of this study is to evaluate coronary computed... Show moreEndothelial wall shear stress (ESS) is a biomechanical force which plays a role in the formation and evolution of atherosclerotic lesions. The purpose of this study is to evaluate coronary computed tomography angiography (CCTA)-based ESS in coronary arteries without atherosclerosis, and to assess factors affecting ESS values. CCTA images from patients with suspected coronary artery disease were analyzed to identify coronary arteries without atherosclerosis. Minimal and maximal ESS values were calculated for 3-mm segments. Factors potentially affecting ESS values were examined, including sex, lumen diameter and distance from the ostium. Segments were categorized according to lumen diameter tertiles into small (< 2.6 mm), intermediate (2.6-3.2 mm) or large (>= 3.2 mm) segments. A total of 349 normal vessels from 168 patients (mean age 59 +/- 9 years, 39% men) were included. ESS was highest in the left anterior descending artery compared to the left circumflex artery and right coronary artery (minimal ESS 2.3 Pa vs. 1.9 Pa vs. 1.6 Pa, p < 0.001 and maximal ESS 3.7 Pa vs. 3.0 Pa vs. 2.5 Pa, p < 0.001). Men had lower ESS values than women, also after adjusting for lumen diameter (p < 0.001). ESS values were highest in small segments compared to intermediate or large segments (minimal ESS 3.8 Pa vs. 1.7 Pa vs. 1.2 Pa, p < 0.001 and maximal ESS 6.0 Pa vs. 2.6 Pa vs. 2.0 Pa, p < 0.001). A weak to strong correlation was found between ESS and distance from the ostium (rho = 0.22-0.62, p < 0.001). CCTA-based ESS values increase rapidly and become widely scattered with decreasing lumen diameter. This needs to be taken into account when assessing the added value of ESS beyond lumen diameter in highly stenotic lesions. Show less
Vascular inflammation, lipid metabolism, and thrombogenicity play a key role not only in atherogenesis but also in the development of acute coronary syndromes. Biomarkers associated with coronary... Show moreVascular inflammation, lipid metabolism, and thrombogenicity play a key role not only in atherogenesis but also in the development of acute coronary syndromes. Biomarkers associated with coronary high-risk plaques defined according to intravascular imaging have not been systematically studied. A total of 69 patients with coronary artery disease who underwent both optical coherence tomography and intravascular ultrasound imaging, and who provided blood specimens were included. Comprehensive biomarkers for inflammation, lipid, and coagulation were analyzed. Composite models sought biomarker patterns associated with thin-cap fibroatheroma (TCFA) and "high-risk plaques" (TCFA and large plaque burden). Two different composite models were developed for TCFA, based on the finding that high sensitivity C-reactive protein (hsCRP), plasminogen activator inhibitor-1, fibrinogen, IL-6, homocysteine and amyloid A levels were elevated, and high-density lipoprotein cholesterol (HDL) and bile acid levels were decreased in these patients. Both composite models were highly accurate for detecting patients with TCFA (area under curve [AUC]: 0.883 in model-A and 0.875 in model-B, both p < 0.001). In addition, creatinine, hsCRP, fibrinogen, tumor necrosis factor-a, IL-6, homocysteine, amyloid A, HDL, prothrombin, and bile acid were useful for detecting patients with "high-risk plaques". Two composite models were highly accurate for detection of patients with "high-risk plaques" (AUC: 0.925 in model-A and 0.947 in model-B, both p <0.001). Biomarkers useful for detection of patients with high-risk coronary plaques defined according to intravascular imaging have been identified. These biomarkers may be useful to risk stratify patients and to develop targeted therapy. Show less
Rosendael, S.E. van; Kuneman, J.H.; Hoogen, I.J. van den; Kitslaar, P.H.; Rosendael, A.R. van; Bijl, P. van der; ... ; Bax, J.J. 2022
Pericoronary adipose tissue (PCAT) attenuation, derived from coronary computed tomography angiography (CCTA), is associated with coronary artery inflammation. Values for PCAT attenuation in men and... Show morePericoronary adipose tissue (PCAT) attenuation, derived from coronary computed tomography angiography (CCTA), is associated with coronary artery inflammation. Values for PCAT attenuation in men and women without atherosclerosis on CCTA are lacking. The aim of the current study was to assess the mean PCAT attenuation in individuals without coronary artery atherosclerosis on CCTA. Data on PCAT attenuation in men and women without coronary artery atherosclerosis on CCTA were included in this retrospective analysis. The PCAT attenuation was analyzed from the proximal part of the right coronary artery (RCA), the left anterior descending artery (LAD), and the left circumflex artery (LCx). For patient level analyses the mean PCAT attenuation was defined as the mean of the three coronary arteries. In 109 individuals (mean age 45 +/- 13 years; 44% men), 320 coronary arteries were analyzed. The mean PCAT attenuation of the overall population was - 64.4 +/- 8.0 HU. The mean PCAT attenuation was significantly lower in the LAD compared with the LCx and RCA (- 67.8 +/- 7.8 HU vs - 62.6 +/- 6.8 HU vs - 63.6 +/- 7.9 HU, respectively, p < 0.001). In addition, the mean PCAT attenuation was significantly higher in men vs. women in all three coronary arteries (LAD: - 65.7 +/- 7.6 HU vs - 69.4 +/- 7.6 HU, p = 0.014; LCx: - 60.6 +/- 7.4 HU vs - 64.3 +/- 5.9 HU, p = 0.008; RCA: -61.7 +/- 7.9 HU vs - 65.0 +/- 7.7 HU, p = 0.029, respectively). The current study provides mean PCAT attenuation values, derived from individuals without CAD. Moreover, the mean PCAT attenuation is lower in women vs. men. Furthermore, the mean PCAT attenuation is significantly lower in the LAD vs LCx and RCA. Show less
Kuneman, J.H.; Mahdiui, M. el; Rosendael, A.R. van; Hoogen, I.J. van den; Patel, M.R.; Norgaard, B.L.; ... ; Knuuti, J. 2022
Background: Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left... Show moreBackground: Diabetes mellitus is a major risk factor for coronary artery disease (CAD) and may provoke structural and functional changes in coronary vasculature. The coronary volume to left ventricular mass (V/M) ratio is a new anatomical parameter capable of revealing a potential physiological imbalance between coronary vasculature and myocardial mass. The aim of this study was to examine the V/M derived from coronary computed tomography angiography (CCTA) in patients with diabetes. Methods: Patients with clinically suspected CAD enrolled in the ADVANCE (Assessing Diagnostic Value of Non-invasive FFRCT in Coronary Care) registry and known diabetic status were included. Coronary artery volume and left ventricular myocardial mass were analyzed from CCTA and the V/M ratio was calculated and compared between patients with and without diabetes. Results: Of the 3053 patients (age 66 +/- 10 years; 66% male) with known diabetic status, diabetes was present in 21.9%. Coronary volume was lower in patients with diabetes compared to those without diabetes (2850 +/- 940 mm(3) vs. 3040 +/- 970 mm(3), p < 0.0001), whereas the myocardial mass was comparable between the 2 groups (122 +/- 33 g vs. 122 +/- 32 g, p = 0.70). The V/M ratio was significantly lower in patients with diabetes (23.9 +/- 6.8 mm(3)/g vs. 25.7 +/- 7.5 mm(3)/g, p < 0.0001). Among subjects with obstructive CAD (n = 2191, 24.0% diabetics) and non-obstructive CAD (16.7% diabetics), the V/M ratio was significantly lower in patients with diabetes compared to those without (23.4 +/- 6.7 mm(3)/g vs. 25.0 +/- 7.3 mm(3)/g, p < 0.0001 and 25.6 +/- 6.9 mm(3)/g vs. 27.3 +/- 7.6 mm(3)/g, respectively, p = 0.006). Conclusion: The V/M ratio was significantly lower in patients with diabetes compared to non-diabetics, even after correcting for obstructive coronary stenosis. The clinical value of the reduced V/M ratio in diabetic patients needs further investigation. Show less
Mahe, G.; Brodmann, M.; Capodanno, D.; Ceriello, A.; Cuisset, T.; Delgado, V.; ... ; Valensi, P. 2022
Aims: This survey aimed to evaluate the current management and screening of coronary artery disease and peripheral artery disease in people with type 2 diabetes mellitus (T2DM) in Europe, utilizing... Show moreAims: This survey aimed to evaluate the current management and screening of coronary artery disease and peripheral artery disease in people with type 2 diabetes mellitus (T2DM) in Europe, utilizing the 2013 ESC/EASD (European Society of Cardiology/European Association for the Study of Diabetes) guidelines as a benchmark. Methods: The PADDIA/CADDIA survey is a European medical research collaboration targeting cardiologists, vascular physicians, diabetologists and general practitioners from Austria, Belgium, France, Germany, Italy, Netherlands and United Kingdom. Results: The questionnaire was completed by sixty-three physicians, of whom 75% declared assessing the cardiovascular risk of people with T2DM mostly without using a risk score (59%). More than 90% of the panel, check HbA1c, blood pressure and low-density lipoprotein cholesterol targets in their patients with T2DM and coronary or peripheral artery disease. For 94% the presence of T2DM influence their patients' management, by optimizing blood glucose, blood pressure and low-density lipoprotein cholesterol control. Only 37% considered screening for lower extremity peripheral artery disease among their T2DM patients and 35% among those with cardiovascular disease. Conclusions: Physicians mostly follow the ESC/EASD 2013 guidelines, but when it comes to screening for additional conditions including coronary artery disease or peripheral artery disease, or intensifying the antithrombotic regimen there is need for better guidance. (C) 2022 Elsevier B.V. All rights reserved. Show less
Objectives To present an overview of studies using serial coronary computed tomography angiography (CCTA) as a tool for finding both quantitative (changes) and qualitative plaque characteristics as... Show moreObjectives To present an overview of studies using serial coronary computed tomography angiography (CCTA) as a tool for finding both quantitative (changes) and qualitative plaque characteristics as well as epicardial adipose tissue (EAT) volume changes as predictors of plaque progression and/or major adverse cardiac events (MACE) and outline the challenges and advantages of using a serial non-invasive imaging approach for assessing cardiovascular prognosis. Methods A literature search was performed in PubMed, Embase, Web of Science, Cochrane Library and Emcare. All observational cohort studies were assessed for quality using the Newcastle-Ottawa Scale (NOS). The NOS score was then converted into Agency for Healthcare Research and Quality (AHRQ) standards: good, fair and poor. Results A total of 36 articles were analyzed for this review, 3 of which were meta-analyses and one was a technical paper. Quantitative baseline plaque features seem to be more predictive of MACE and/or plaque progression as compared to qualitative plaque features. Conclusions A critical review of the literature focusing on studies utilizing serial CCTA revealed that mainly quantitative baseline plaque features and quantitative plaque changes are predictive of MACE and/or plaque progression contrary to qualitative plaque features. Significant questions regarding the clinical implications of these specific quantitative and qualitative plaque features as well as the challenges of using serial CCTA have yet to be resolved in studies using this imaging technique. Show less
The significance of classical risk factors in coronary artery disease (CAD) remains unclear in older age due to possible changes in underlying disease pathologies. Therefore, we conducted Mendelian... Show moreThe significance of classical risk factors in coronary artery disease (CAD) remains unclear in older age due to possible changes in underlying disease pathologies. Therefore, we conducted Mendelian Randomization approaches to investigate the causal relationship between classical risk factors and primary CAD in different age groups. A Mendelian Randomization study was conducted in European-ethnicity individuals from the UK Biobank population. Analyses were performed using data of 22,313 CAD cases (71.6% men) and 407,920 controls (44.5% men). Using logistic regression analyses, we investigated the associations between standardized genetic risk score and primary CAD stratified by age of diagnosis. In addition, feature importance and model accuracy were assessed in different age groups to evaluate predictive power of the genetic risk scores with increasing age. We found age-dependent associations for all classical CAD risk factors. Notably, body mass index (OR 1.22 diagnosis < 50 years; OR 1.02 diagnosis > 70 years), blood pressure (OR 1.12 < 50 years; OR 1.04 > 70 years), LDL cholesterol (OR 1.16 < 50 years; OR 1.02 > 70 years), and triglyceride levels (OR 1.11 < 50 years; 1.04 > 70 years). In line with the Mendelian Randomization analyses, model accuracy and feature importance of the classical risk factors decreased with increasing age of diagnosis. Causal determinants for primary CAD are age dependent with classical CAD risk factors attenuating in relation with primary CAD with increasing age. These results question the need for (some) currently applied cardiovascular disease risk reducing interventions at older age. Show less
Background The 2019 ESC-guidelines on chronic coronary syndromes (ESC-CCS) recommend computed tomographic coronary angiography (CTCA) or non-invasive functional imaging instead of exercise ECG as... Show moreBackground The 2019 ESC-guidelines on chronic coronary syndromes (ESC-CCS) recommend computed tomographic coronary angiography (CTCA) or non-invasive functional imaging instead of exercise ECG as initial test to diagnose obstructive coronary artery disease. Since impact and challenges of these guidelines are unknown, we studied the current utilisation of CTCA-services, status of CTCA-protocols and modeled the expected impact of these guidelines in the Netherlands. Methods and results A survey on current practice and CTCA utilisation was disseminated to every Dutch hospital organisation providing outpatient cardiology care and modeled the required CTCA capacity for implementation of the ESC guideline, based on these national figures and expert consensus. Survey response rate was 100% (68/68 hospital organisations). In 2019, 63 hospital organisations provided CTCA-services (93%), CTCA was performed on 99 CTCA-capable CT-scanners, and 37,283 CTCA-examinations were performed. Between the hospital organisations, we found substantial variation considering CTCA indications, CTCA equipment and acquisition and reporting standards. To fully implement the new ESC guideline, our model suggests that 70,000 additional CTCA-examinations would have to be performed in the Netherlands. Conclusions Despite high national CTCA-services coverage in the Netherlands, a substantial increase in CTCA capacity is expected to be able to implement the 2019 ESC-CCS recommendations on the use of CTCA. Furthermore, the results of this survey highlight the importance to address variations in image acquisition and to standardise the interpretation and reporting of CTCA, as well as to establish interdisciplinary collaboration and organisational alignment. Show less
Giorgi, N. di; Michelucci, E.; Smit, J.M.; Scholte, A.J.H.A.; Mahdiui, M. el; Knuuti, J.; ... ; Rocchiccioli, S. 2021
Background and aims: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) define a specific lipid profile associated with residual coronary artery disease (CAD) risk... Show moreBackground and aims: Elevated triglycerides (TG) and low high-density lipoprotein cholesterol (HDL-C) define a specific lipid profile associated with residual coronary artery disease (CAD) risk independently of total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Aim of the present study was to assess whether TG/ HDL-C ratio, coronary atherosclerosis and their change over time are characterized by a specific lipidomic profiling in stable patients with chronic coronary syndrome (CCS). Methods: TG/HDL-C ratio was calculated in 193 patients (57.8 +/- 7.6 years, 115 males) with CCS characterized by clinical, bio-humoral profiles and cardiac imaging. Patient-specific plasma targeted lipidomics was defined through a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) strategy. Patients underwent coronary computed tomography angiography (CTA) and an individual CTA risk score, combining extent, severity, composition, and location of plaques, was calculated. All patients entered a follow-up (6.39 +/- 1.17 years), including clinical, lipidomics and coronary CTA assessments. Results: Patients were divided in groups according to baseline TG/HDL-C quartiles: IQ (<1.391), IIQ (1.392-2.000), IIIQ (2.001-3.286), and IVQ (>= 3.287). A specific pattern of altered lipids, characterized by reduced plasma levels of cholesterol esters, phosphatidylcholines and sphingomyelins, was associated with higher TG/HDL-C both at baseline and follow-up (IVQ vs IQ). The CTA risk score increased over time and this lipid signature was also associated with higher CTA score at follow-up. Conclusions: In stable CCS, a specific lipidomic signature identifies those patients with higher TG/HDL- C ratio and higher CTA score over time, suggesting possible molecular pathways of residual CAD risk not tackled by current optimal medical treatments. Show less
Background Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed... Show moreBackground Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. Methods Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. Results Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99-1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96-1.04; p value 0.59). Conclusions Lower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk. Show less
