Performance and usability of pre-operative prediction models for 30-day peri-operative mortality risk: a systematic review.

Estimating pre-operative mortality risk may inform clinical decision-making for peri-operative care. However, pre-operative mortality risk prediction models are rarely implemented in routine clinical practice. High predictive accuracy and clinical usability are essential for acceptance and clinical implementation. In this systematic review, we identified and appraised prediction models for 30-day postoperative mortality in non-cardiac surgical cohorts. PubMed and Embase were searched up to December 2022 for studies investigating pre-operative prediction models for 30-day mortality. We assessed predictive performance in terms of discrimination and calibration. Risk of bias was evaluated using a tool to assess the risk of bias and applicability of prediction model studies. To further inform potential adoption, we also assessed clinical usability for selected models. In all, 15 studies evaluating 10 prediction models were included. Discrimination ranged from a c-statistic of 0.82 (MySurgeryRisk) to 0.96 (extreme gradient boosting machine learning model). Calibration was reported in only six studies. Model performance was highest for the surgical outcome risk tool (SORT) and its external validations. Clinical usability was highest for the surgical risk pre-operative assessment system. The SORT and risk quantification index also scored high on clinical usability. We found unclear or high risk of bias in the development of all models. The SORT showed the best combination of predictive performance and clinical usability and has been externally validated in several heterogeneous cohorts. To improve clinical uptake, full integration of reliable models with sufficient face validity within the electronic health record is imperative.

Validation of Central Pressure Estimation in Patients with an Aortic Aneurysm Before and After Endovascular Repair.

PURPOSE: The aim of this study was to investigate if non-invasive central pressure estimations are accurate in patients with an abdominal aortic aneurysm, before and after endovascular repair. Secondary evaluation was if measurement-accuracy was dependent on anatomical characteristics. METHODS: Procedural invasive and non-invasive pressure-measurements were performed simultaneously both before and after endovascular repair in 20 patients with an infrarenal abdominal aortic aneurysm. Invasive catheter measurements were performed in the abdominal aorta. A tonometric device was used to perform non-invasive pressure-wave-analysis at the radial artery. A generalized transfer-function was used to generate an ascending aortic waveform for both measurements, allowing for direct comparison. RESULTS: Pre-treatment the mean differences between methods were - 5.5 mmHg (p = .904), - 11.8 (p < .001), and - 7.2 mmHg (p = .124) for central systolic, diastolic, and mean pressure, respectively. The accuracy was dependent of aneurysm sac volume and intraluminal thrombus volume. Post-treatment limits of agreement were smaller for all pressure parameters compared to pre-treatment. The mean differences were 6.5 mmHg (p = .007), - 6.4 (p < .020), and 1.6 mmHg (p = .370) for central systolic, diastolic, and mean pressure, respectively. CONCLUSION: In untreated AAA's the accuracy of non-invasive central pressure estimation was acceptable (mean difference between 5 and 10 mmHg) when compared to invasive pressures, but dependent of AAA characteristics. After EVAR the accuracy of central pressure estimation improved (reduction of 75% of the mean difference between pre and post measurements) TRIAL REGISTRATION NUMBER: NCT03469388; 3-5-2018.

Vascular Health in Patients in Remission of Cushing's Syndrome Is Comparable With That in BMI-Matched Controls.

CONTEXT: In active Cushing's syndrome (CS), patients suffer from endothelial dysfunction and premature atherosclerosis. However, it is uncertain to what extent vascular health recovers after long-term remission. This is highly relevant because this topic relates to future development of cardiovascular disease. OBJECTIVE: The objective of the study was to investigate whether micro- and macrovascular health is impaired after long-term remission of CS in patients with no or adequately treated comorbidities. DESIGN AND SETTING: This was a cross-sectional case-control study in two tertiary referral centers. PATIENTS AND MAIN OUTCOME MEASURES: Sixty-three patients (remission of CS for ≥ 4 y) and 63 healthy, well-matched controls were compared. In group A (58 patients and 58 controls), serum biomarkers associated with endothelial dysfunction, intima media thickness, pulse wave velocity, and pulse wave analysis were studied. In group B (14 patients and 14 controls), endothelium-dependent and -independent vasodilatation was studied in conduit arteries (flow mediated dilation of the brachial artery) and forearm skeletal muscle resistance arteries (vasodilator response to intraarterial acetylcholine, sodium-nitroprusside, and NG-monomethyl-L-arginine using venous occlusion plethysmography). RESULTS: There were no significant differences between the outcome measures of vascular health of patients and controls in groups A and B. CONCLUSION: The vascular health of patients in long-term remission of CS seems to be comparable with that of healthy gender-, age-, and body mass index-matched controls, provided that the patients have no, or adequately controlled, comorbidities. Therefore, the effects of hypercortisolism per se on the vasculature may be reversible. This accentuates the need for the stringent treatment of metabolic comorbidities in these patients.

Computation of blood flow through collateral circulation of the superficial femoral artery.

OBJECTIVE: Obliteration of collaterals during (endo)vascular treatment of peripheral arterial occlusive disease is considered detrimental. We use a model to calculate maximum collateral bed flow of the superficial femoral artery in order to provide insight in their hemodynamic relevance. METHOD: A computational model was developed using digital subtraction angiographies in combination with Poiseuille's equation and Ohm's law. Lesions were divided into short and long (<15 cm and ≥15 cm, respectively) and into stenosis and occlusions. Data are presented in relation to the calculated maximum healthy superficial femoral artery flow. RESULTS: Stenotic lesions are longer than occlusive lesions (P < 0.05) and occlusions had more and larger collaterals (P < 0.05). In all four study groups the collateral flow significantly increased the total flow (P < 0.05). The maximum collateral system flow in the stenosis and occlusion groups was 5.1% and 20.8% of healthy superficial femoral artery flow, respectively (P < 0.05), and there were no significant differences between short and long lesions (11.2% and 6.7% of healthy superficial femoral artery flow, respectively). CONCLUSION: The maximum collateral system flow of the superficial femoral artery is only a fraction, with a maximum of one fifth, of healthy superficial femoral artery flow. Effects of collateral vessel occlusion during (endo)vascular treatment may therefore be without detrimental consequences.

Common carotid intima-media thickness does not add to Framingham risk score in individuals with diabetes mellitus: the USE-IMT initiative.

AIMS/HYPOTHESIS: The aim of this work was to investigate whether measurement of the mean common carotid intima-media thickness (CIMT) improves cardiovascular risk prediction in individuals with diabetes. METHODS: We performed a subanalysis among 4,220 individuals with diabetes in a large ongoing individual participant data meta-analysis involving 56,194 subjects from 17 population-based cohorts worldwide. We first refitted the risk factors of the Framingham heart risk score on the individuals without previous cardiovascular disease (baseline model) and then expanded this model with the mean common CIMT (CIMT model). The absolute 10 year risk for developing a myocardial infarction or stroke was estimated from both models. In individuals with diabetes we compared discrimination and calibration of the two models. Reclassification of individuals with diabetes was based on allocation to another cardiovascular risk category when mean common CIMT was added. RESULTS: During a median follow-up of 8.7 years, 684 first-time cardiovascular events occurred among the population with diabetes. The C statistic was 0.67 for the Framingham model and 0.68 for the CIMT model. The absolute 10 year risk for developing a myocardial infarction or stroke was 16% in both models. There was no net reclassification improvement with the addition of mean common CIMT (1.7%; 95% CI -1.8, 3.8). There were no differences in the results between men and women. CONCLUSIONS/INTERPRETATION: There is no improvement in risk prediction in individuals with diabetes when measurement of the mean common CIMT is added to the Framingham risk score. Therefore, this measurement is not recommended for improving individual cardiovascular risk stratification in individuals with diabetes.

Depressive symptom clusters are differentially associated with atherosclerotic disease.

BACKGROUND: Depression increases the risk of subsequent vascular events in both cardiac and non-cardiac patients. Atherosclerosis, the underlying process leading to vascular events, has been associated with depression. This association, however, may be confounded by the somatic-affective symptoms being a consequence of cardiovascular disease. While taking into account the differentiation between somatic-affective and cognitive-affective symptoms of depression, we examined the association between depression and atherosclerosis in a community-based sample. METHOD: In 1261 participants of the Nijmegen Biomedical Study (NBS), aged 50-70 years and free of stroke and dementia, we measured the intima-media thickness (IMT) of the carotid artery as a measure of atherosclerosis and we assessed depressive symptoms using the Beck Depression Inventory (BDI). Principal components analysis (PCA) of the BDI items yielded two factors, representing a cognitive-affective and a somatic-affective symptom cluster. While correcting for confounders, we used separate multiple regression analyses to test the BDI sum score and both depression symptom clusters. RESULTS: We found a significant correlation between the BDI sum score and the IMT. Cognitive-affective, but not somatic-affective, symptoms were also associated with the IMT. When we stratified for coronary artery disease (CAD), the somatic-affective symptom cluster correlated significantly with depression in both patients with and patients without CAD. CONCLUSIONS: The association between depressive symptoms and atherosclerosis is explained by the somatic-affective symptom cluster of depression. Subclinical vascular disease thus may inflate depressive symptom scores and may explain why treatment of depression in cardiac patients hardly affects vascular outcome.

Apolipoprotein B, non-HDL cholesterol and LDL cholesterol for identifying individuals at increased cardiovascular risk.

BACKGROUND: To compare apolipoprotein B (apoB), non-high-density lipoprotein-cholesterol (non-HDL-c) and low-density lipoprotein-cholesterol (LDL-c) for identifying individuals with a deteriorated cardiovascular (CV) risk profile, including a panel of subclinical atherosclerosis measurements and prevalent cardiovascular disease (CVD) in a Dutch population-based cohort. METHODS: Clinical and biochemical measurements and a panel of noninvasive parameters of subclinical atherosclerosis were determined in 1517 individuals, aged 50-70 years. RESULTS: Both men and women with increasing levels of apoB and non-HDL-c were more obese, had higher blood pressure and fasting glucose levels, and a more atherogenic lipid profile. Furthermore, compared to the reference group (composed of those with apoB, non-HDL-c and LDL-c levels in the bottom quartiles), participants with high apoB and high non-HDL-c levels had a lower ankle-brachial index at rest (-3.5% and -3.1%, respectively) and after exercise (-6.3% and -4.7%, respectively), a thicker near wall (+4.8% and +4.2%, respectively), far wall (both +6.2%), and mean intima-media thickness (+5.7% and +5.3%, respectively) and more plaques (+54.2% and +54.3%, respectively). In addition, they also showed increased stiffness parameters (e.g. pulse wave velocity both +3.6%). Less clear differences in CV risk profile and subclinical atherosclerosis parameters were observed when participants were stratified by LDL-c level. Furthermore, apoB but not LDL-c detected prevalent CVD, and non-HDL-c only detected prevalent CVD in men. The discriminatory power for prevalent CVD expressed as area under the receiver operating characteristic curve was 0.60 (P < 0.001) for apoB, 0.57 (P = 0.001) for non-HDL-c and 0.54 (P = 0.108) for LDL-c. CONCLUSION: Our data support the use of first apoB and secondly non-HDL-c above LDL-c for identifying individuals from the general population with a compromised CV phenotype.

Impact of waist circumference versus adiponectin level on subclinical atherosclerosis: a cross-sectional analysis in a sample from the general population.

OBJECTIVE: Waist circumference is a clinical marker of obesity and an established risk factor for cardiovascular (CV) disease. Adiponectin, an adipocyte-derived hormone and new biomarker of obesity, was recently proposed as the missing link between obesity and increased cardiovascular risk. We evaluated waist and adiponectin in a middle-aged population-based cohort to compare the impact of both obesity-markers on subclinical atherosclerosis, in relation to other CV risk factors. DESIGN, SETTING & SUBJECTS: Seven noninvasive measurements of atherosclerosis (NIMA), as surrogate markers of (subclinical) atherosclerosis, were determined in 1517 participants of the Nijmegen Biomedical Study, aged 50-70 years, who were drawn from the Dutch community. RESULTS: Both men and women with a high waist (M >104 cm; F >95 cm) showed increased pulse wave velocity (PWV) (M: +9.4%; F: +8.3%) and thicker intima-media thickness (IMT) (M: +7.3%; F: +4.3%) and women also showed increased plaque thickness (+16.6%). After adjustment for other CV risk factors both men and women showed increased IMT (M: +4.8%; F: +2.8%) and men also showed increased PWV (+9.6%). Both men and women with a low adiponectin level (M <2.2 mg L(-1); F <3.5 mg L(-1)) showed a decreased ankle-brachial index after exercise (M: -9.5%; F: -3.9%) and increased IMT (M: +3.7%; F: +3.6%) and women also showed increased PWV (+6.8%), but after adjustment for other CV risk factors low adiponectin level was no longer associated with deteriorated outcomes of NIMA. CONCLUSIONS: Waist circumference showed independent associations with noninvasive measurements of subclinical atherosclerosis, whereas the association of adiponectin level with subclinical atherosclerosis was not independent of other CV risk factors. Prospective studies are needed to elucidate, if the atherogenic effect of a low adiponectin level is mediated by other CV risk factors and not by low adiponectin level intrinsically.

Non-invasive measurements of atherosclerosis (NIMA): current evidence and future perspectives.

In clinical practice, cardiovascular (CV) risk stratification is based on the assessment of individual risk factors. Still many cardiovascular deaths occur in individuals who were not at high risk according to the current CV risk stratification models as the Systematic COronary Risk Evaluation chart (SCORE) and Framingham Risk Score. By measuring morphological and÷or functional abnormalities in the arterial wall directly, the impact of all CV risk factors together can be determined. In this review, the current status for the use of a panel of non-invasive measurements of atherosclerosis (NIMA) in CV risk prediction in clinical practice is discussed. Some of these NIMA showed predictive value for CV disease, such as intima-media thickness, pulse wave velocity, and ankle-brachial index, both in patients and in healthy and community-based populations. Recommendations have been made to include these NIMA in CV risk stratification in secondary prevention. However, the additional value of NIMA in CV risk stratification in primary prevention settings remains to be determined. Furthermore, the main determinants of NIMA are still unclear. Also the use of different combinations of NIMA should be evaluated, since different NIMA likely reflect different stages and aspects of the atherosclerotic process that leads to CV events. Future prospective studies should focus on repeated measures of NIMA to reveal the main determinants of the different NIMA and evaluate the predictive value of baseline versus repeated measurements.

Brachial artery diameter is related to cardiovascular risk factors and intima-media thickness.

BACKGROUND: Previous reports showed inconsistent results about the potential role of flow-mediated dilatation (FMD) in cardiovascular(CV) risk prediction. Few data are available about the role of nitroglycerin-mediated dilatation (NMD), but recently, brachial artery diameter(BAD) appeared to have predictive value in CV risk prediction.We determined the relation of FMD, BAD and NMD with known CV risk factors and intima-media thickness (IMT), a well-established surrogate marker of atherosclerosis, in a community-based population, the Nijmegen Biomedical Study (NBS). MATERIALS AND METHODS: FMD, BAD and NMD were measured in the brachial, and IMT in the common carotid artery ultrasononically in 337 participants, aged 50-70 years. Traditional clinical and biochemical parameters were determined. RESULTS: Both FMD and NMD were not correlated with most CV risk factors or prevalent CVD. However, both IMT and BAD did show significant correlations with CV risk factors. In accordance, both IMT and BAD were significantly correlated with prevalent CVD (r=0.62 and r=-0.37, respectively) . Furthermore, FMD was not correlated with IMT and did hardly (R2=1.1%) improve the prediction of IMT by CV risk factors in regression analysis. However, both BAD and NMD did correlate with IMT (r=-0.29 and r=0.25, respectively). CONCLUSION: In our study, FMD and NMD were not related to known CV risk factors and prevalent CVD, and FMD was not correlated with IMT, a surrogate marker of atherosclerosis. Most intriguingly, BAD was significantly correlated with some CV risk factors, prevalent CVD and IMT. So, BAD is a potential valuable tool in CV risk prediction in middle-aged low-risk populations, whereas FMD is not.

Inflammation in deep vein thrombosis and the development of post-thrombotic syndrome: a prospective study.

BACKGROUND: The aim of this study was to investigate whether inflammatory markers (interleukin-6 [IL-6] and C-reactive protein [CRP]) in the acute phase of deep vein thrombosis (DVT) are associated with elevated venous outflow resistance (VOR), thrombosis score (TS), reflux and the development of clinical post-thrombotic syndrome (PTS). METHODS: In 110 patients with a first DVT, plasma concentrations of IL-6 and CRP were determined on the day of admission. VOR, TS and reflux were measured 7 days, 1 and 3 months after diagnosis. After 1 year patients were evaluated for PTS using the Clinical, Etiologic, Anatomic and Pathophysiologic (CEAP) classification and Villalta scale. RESULTS: Median levels of IL-6 and CRP were 7 pg mL(-1) and 21 mg L(-1), respectively. After 3 months, VOR was elevated in 33 patients (30%), TS in 33 (30%) and reflux in 57 (52%). Incidence of PTS was 36.7% using CEAP>or=3 and 35.4% using Villalta-scale>or=5. Elevated levels of IL-6 and CRP were related to higher outcomes of VOR after 3 months [relative risks (RR) 2.4 (95% CI 1.5-3.9) and 1.4 (1.1-3.3), respectively] and for IL-6 to TS [1.5 (1.1-2.1)]. For reflux no relation was found. After 90 days, elevated outcomes of VOR, TS and reflux were related to PTS after 1 year. The association of IL-6 and CRP with PTS was weak using the CEAP classification with a RR of 1.2 (0.7-2.2) and 1.8 (0.9-3.3) and absent according to the Villalta scale 0.6 (0.2-1.4) and 1.2 (0.6-2.5), respectively. CONCLUSION: The results of this study suggest that inflammation might play a role in incomplete thrombus clearance, venous outflow obstruction and the development of PTS after 1 year.

Endothelial function in familial combined hyperlipidaemia.

BACKGROUND: Familial combined hyperlipidaemia (FCH) is characterized by dyslipidaemia, visceral obesity and insulin resistance, and is associated with an increased intima-media thickness (IMT) and an increased risk for cardiovascular disease. In the present study, we investigated whether FCH is associated with early functional vascular wall changes, as represented by endothelial dysfunction, and we determined whether endothelial function in FCH is related to any of the cardiovascular risk factors associated with the FCH phenotype, or to the (increased) IMT. DESIGN: In 98 patients with FCH [mean age 51 (48-54) years, 43% male] and 230 unaffected relatives [mean age 44 (42-46) years, 48% male], venous blood was drawn in the fasting state after discontinuation of lipid lowering drugs for at least 4 weeks (if used). IMT was measured by B-mode ultrasound and endothelial function was assessed by determination of flow mediated dilation (FMD) and by measurement of plasma concentrations of various soluble adhesion molecules, including soluble vascular cell adhesion molecule (sVCAM), soluble intercellular adhesion molecule (sICAM) and soluble E-selectin. RESULTS: There were no significant differences between FCH patients and their non-affected relatives in FMD [2.9 (2.3-3.6%) vs. 2.8 (2.5-3.2%)] or in the plasma concentrations of the various adhesion molecules. None of the individual clinical and biochemical cardiovascular risk factors was an independent predictor of endothelial function in patients with FCH, nor was IMT. However, subgroup analysis revealed that IMT was an independent and powerful predictor of FMD in subjects with carotid artery plaques (St. beta = 4.11, P < 0.004), whereas IMT was no significant predictor in subjects without plaques. CONCLUSIONS: FCH patients have no impaired endothelial function when compared to their unaffected relatives. IMT is an important predictor of FMD when advanced morphological wall changes are present. Our results question the value of FMD measurements for cardiovascular risk stratification in populations with an anticipated high cardiovascular risk.

The StethoDop: a Doppler stethoscope attachment for investigation of arterial and venous insufficiency of the lower extremities.

BACKGROUND: The aim of the current study was to investigate whether the StethoDop can serve as a valid and reproducible instrument for measuring the ankle-brachial index (ABI) and assessing venous reflux, even when used by inexperienced investigators, in comparison with the classic Doppler. METHODS: I) During four weeks, four ankle-brachial index (ABI) measurements were performed on 44 patients: one measurement with the classic Doppler by an experienced investigator, one with the classic Doppler by an inexperienced investigator and two measurements with the StethoDop by the inexperienced investigator. II) 36 patients were screened for venous insufficiency by detecting venous reflux with the StethoDop and classic Doppler at the saphenofemoral and saphenopoplitial junctions by an inexperienced investigator. The results were compared with the results of the duplex as gold standard and with the results of the examination by an experienced dermatologist with the classic Doppler. RESULTS: I) The confidence interval of ABI measurement for both the classic Doppler and the StethoDop by the inexperienced investigator was within an acceptable +/- 0.21 interval of significant change. II) For venous reflux determination, the overall sensitivity and specificity of the StethoDop were comparable with the sensitivity and specificity of the classic Doppler: sensitivity 76.0 and 75.0%, specificity 94.8 and 94.2%, respectively. The positive predictive value of the StethoDop, compared with the duplex, was 87.5%; the negative predictive value was 90.0%. CONCLUSION: I) For ABI measurement, the StethoDop is a valid instrument with reproducible results, even when used by inexperienced investigators. II) For venous reflux determination, the StethoDop is a valid screening instrument for venous insufficiency. However, as with determination with the classic Doppler, the reflux assessment by StethoDop gives no information about the deep veins and may miss up to 24% of apparent reflux.