Postoperative myocardial injury phenotypes and self-reported disability in patients undergoing noncardiac surgery: a multicentre observational study.

BACKGROUND: Postoperative myocardial injury (PMI) comprises a spectrum of mechanisms resulting in troponin release. The impact of different PMI phenotypes on postoperative disability remains unknown. METHODS: This was a multicentre prospective cohort study including patients aged ≥50 yr undergoing elective major noncardiac surgery. Patients were stratified in five groups based on the occurrence of PMI and clinical information on postoperative adverse events: PMI classified as myocardial infarction (MI; according to fourth definition), PMI plus adverse event other than MI, clinically silent PMI (PMI without adverse events), adverse events without PMI, and neither PMI nor an adverse event (reference). The primary endpoint was 6-month self-reported disability (assessed by WHO Disability Assessment Schedule 2.0 [WHODAS]). Disability-free survival was defined as WHODAS ≤16%. RESULTS: We included 888 patients of mean age 69 (range 53-91) yr, of which 356 (40%) were women; 151 (17%) patients experienced PMI, and 625 (71%) experienced 6-month disability-free survival. Patients with PMI, regardless of its phenotype, had higher preoperative disability scores than patients without PMI (difference in WHODAS; ß: 3.3, 95% confidence interval [CI]: 0.5-6.2), but scores remained stable after surgery (ß: 1.2, 95% CI: -3.2-5.6). Before surgery, patients with MI (n=36, 4%) were more disabled compared with patients without PMI and no adverse events (ß: 5.5, 95% CI: 0.3-10.8). At 6 months, patients with MI and patients without PMI but with adverse events worsened in disability score (ß: 11.2, 95% CI: 2.3-20.2; ß: 8.1, 95% CI: 3.0-13.2, respectively). Patients with clinically silent PMI did not change in disability score at 6 months (ß: 1.39, 95% CI: -4.50-7.29, P=0.642). CONCLUSIONS: Although patients with postoperative myocardial injury had higher preoperative self-reported disability, disability scores did not change at 6 months after surgery. However, patients experiencing myocardial infarction worsened in disability score after surgery.

Cohort profile: the Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study-an ongoing prospective cohort study of patients at high cardiovascular risk in the Netherlands.

PURPOSE: The Utrecht Cardiovascular Cohort-Second Manifestations of Arterial Disease (UCC-SMART) Study is an ongoing prospective single-centre cohort study with the aim to assess important determinants and the prognosis of cardiovascular disease progression. This article provides an update of the rationale, design, included patients, measurements and findings from the start in 1996 to date. PARTICIPANTS: The UCC-SMART Study includes patients aged 18-90 years referred to the University Medical Center Utrecht, the Netherlands, for management of cardiovascular disease (CVD) or severe cardiovascular risk factors. Since September 1996, a total of 14 830 patients have been included. Upon inclusion, patients undergo a standardised screening programme, including questionnaires, vital signs, laboratory measurements, an ECG, vascular ultrasound of carotid arteries and aorta, ankle-brachial index and ultrasound measurements of adipose tissue, kidney size and intima-media thickness. Outcomes of interest are collected through annual questionnaires and adjudicated by an endpoint committee. FINDINGS TO DATE: By May 2022, the included patients contributed to a total follow-up time of over 134 000 person-years. During follow-up, 2259 patients suffered a vascular endpoint (including non-fatal myocardial infarction, non-fatal stroke and vascular death) and 2794 all-cause deaths, 943 incident cases of diabetes and 2139 incident cases of cancer were observed up until January 2020. The UCC-SMART cohort contributed to over 350 articles published in peer-reviewed journals, including prediction models recommended by the 2021 European Society of Cardiology CVD prevention guidelines. FUTURE PLANS: The UCC-SMART Study guarantees an infrastructure for research in patients at high cardiovascular risk. The cohort will continue to include about 600 patients yearly and follow-up will be ongoing to ensure an up-to-date cohort in accordance with current healthcare and scientific knowledge. In the near future, UCC-SMART will be enriched by echocardiography, and a food frequency questionnaire at baseline enabling the assessment of associations between nutrition and CVD and diabetes.

Exercise Volume Versus Intensity and the Progression of Coronary Atherosclerosis in Middle-Aged and Older Athletes: Findings From the MARC-2 Study.

BACKGROUND: Physical activity and exercise training are associated with a lower risk for coronary events. However, cross-sectional studies in middle-aged and older male athletes revealed increased coronary artery calcification (CAC) and atherosclerotic plaques, which were related to the amount and intensity of lifelong exercise. We examined the longitudinal relationship between exercise training characteristics and coronary atherosclerosis. METHODS: Middle-aged and older men from the MARC-1 (Measuring Athlete's Risk of Cardiovascular Events 1) study were invited for follow-up in MARC-2 (Measuring Athlete's Risk of Cardiovascular Events 2) study. The prevalence and severity of CAC and plaques were determined by coronary computed tomography angiography. The volume (metabolic equivalent of task [MET] hours/week) and intensity (moderate [3 to 6 MET hours/week]; vigorous [6 to 9 MET hours/week]; and very vigorous [≥9 MET hours/week]) of exercise training were quantified during follow-up. Linear and logistic regression analyses were performed to determine the association between exercise volume/intensity and markers of coronary atherosclerosis. RESULTS: We included 289 (age, 54 [50 to 60] years [median (Q1 to Q3)]) of the original 318 MARC-1 participants with a follow-up of 6.3±0.5 years (mean±SD). Participants exercised for 41 (25 to 57) MET hours/week during follow-up, of which 0% (0 to 19%) was at moderate intensity, 44% (0 to 84%) was at vigorous intensity, and 34% (0 to 80%) was at very vigorous intensity. Prevalence of CAC and the median CAC score increased from 52% to 71% and 1 (0 to 32) to 31 (0 to 132), respectively. Exercise volume during follow-up was not associated with changes in CAC or plaque. Vigorous intensity exercise (per 10% increase) was associated with a lesser increase in CAC score (ß, -0.05 [-0.09 to -0.01]; P=0.02), whereas very vigorous intensity exercise was associated with a greater increase in CAC score (ß, 0.05 [0.01 to 0.09] per 10%; P=0.01). Very vigorous exercise was also associated with increased odds of dichotomized plaque progression (adjusted odds ratio [aOR], 1.09 [1.01 to 1.18] per 10%; aOR, 2.04 [0.93 to 4.15] for highest versus lowest very vigorous intensity tertiles, respectively), and specifically with increased calcified plaques (aOR, 1.07 [1.00 to 1.15] per 10%; aOR, 2.09 [1.09 to 4.00] for highest versus lowest tertile, respectively). CONCLUSIONS: Exercise intensity but not volume was associated with progression of coronary atherosclerosis during 6-year follow-up. It is intriguing that very vigorous intensity exercise was associated with greater CAC and calcified plaque progression, whereas vigorous intensity exercise was associated with less CAC progression.

The relation between urinary sodium and potassium excretion and risk of cardiovascular events and mortality in patients with cardiovascular disease.

BACKGROUND: Most evidence on the relationship between sodium and potassium intake and cardiovascular disease originated from general population studies. This study aimed to evaluate the relation between estimated 24-hour sodium and potassium urinary excretion and the risk of recurrent vascular events and mortality in patients with vascular disease. METHODS: 7561 patients with vascular disease enrolled in the UCC-SMART cohort (1996-2015) were included. Twenty-four hour sodium and potassium urinary excretion were estimated (Kawasaki formulae) from morning urine samples. Cox proportional hazard models with restricted cubic splines were used to evaluate the relation between estimated urinary salt excretion and major adverse cardiovascular events (MACE; including myocardial infarction, stroke, cardiovascular mortality) and all-cause mortality. RESULTS: After a median follow-up of 7.4 years (interquartile range: 4.1-11.0), the relations between estimated 24-hour sodium urinary excretion and outcomes were J-shaped with nadirs of 4.59 gram/day for recurrent MACE and 4.97 gram/day for all-cause mortality. The relation between sodium-to-potassium excretion ratio and outcomes were also J-shaped with nadirs of 2.71 for recurrent MACE and 2.60 for all-cause mortality. Higher potassium urinary excretion was related to an increased risk of both recurrent MACE (HR 1.25 per gram potassium excretion per day; 95%CI 1.13-1.39) and all cause-mortality (HR 1.13 per gram potassium excretion per day; 95%CI 1.03-1.25). CONCLUSIONS: In patients with established vascular disease, lower and higher sodium intake were associated with higher risk of recurrent MACE and all-cause mortality. Higher estimated 24-hour potassium urinary excretion was associated with a higher risk of recurrent MACE and all-cause mortality.

Screening for abdominal aortic aneurysm in patients with clinically manifest vascular disease.

AIMS: Declining prevalence of abdominal aortic aneurysm (AAA) might force a more targeted screening approach (high-risk populations only) in order to maintain (cost-)effectiveness. We aimed to determine temporal changes in the prevalence of screening-detected AAA, to assess AAA-related surgery, and evaluate all-cause mortality in patients with manifest vascular disease. METHODS AND RESULTS: We included patients with manifest vascular disease but without a history of AAA enrolled in the ongoing single-centre prospective UCC-SMART cohort study. Patients were screened at baseline for AAA by abdominal ultrasonography. We calculated sex- and age-specific prevalence of AAA, probability of survival in relation to the presence of AAA, and the proportion of patients undergoing AAA-related surgery. Prevalence of screening-detected AAA in 5440 screened men was 2.5% [95% confidence interval (CI) 2.1-2.9%] and in 1983 screened women 0.7% (95% CI 0.4-1.1%). Prevalence declined from 1997 until 2017 in men aged 70-79 years from 8.1% to 3.2% and in men aged 60-69 years from 5.7% to 1.0%. 36% of patients with screening-detected AAA received elective AAA-related surgery during follow-up (median time until surgery = 5.3 years, interquartile range 2.5-9.1). Patients with screening-detected AAA had a lower probability of survival (sex and age adjusted) compared to patients without screening-detected AAA (51%, 95% CI 41-64% vs. 69%, 95% CI 68-71%) after 15 years of follow-up. CONCLUSION: The prevalence of screening-detected AAA has declined over the period 1997-2017 in men with vascular disease but exceeds prevalence in already established screening programs targeting 65-year-old men. Screening for AAA in patients with vascular disease may be cost-effective, but this remains to be determined.

External applicability of SGLT2 inhibitor cardiovascular outcome trials to patients with type 2 diabetes and cardiovascular disease.

BACKGROUND: Recent treatment guidelines support the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with type 2 diabetes and cardiovascular disease based on the results of cardiovascular outcome trials (CVOTs). Applicability of these trials to everyday patients with type 2 diabetes and cardiovascular disease is however unknown. The aim of this study is to assess the external applicability of SGLT2i CVOTs in daily clinical practice type 2 diabetes patients with established cardiovascular disease. METHODS: Trial in- and exclusion criteria from EMPA-REG OUTCOME, CANVAS, DECLARE-TIMI 58 and VERTIS-CV were applied to 1389 type 2 diabetes patients with cardiovascular disease in the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (UCC-SMART). To evaluate the difference in cardiovascular risk (MACE) and all-cause mortality between trial eligible and ineligible patients, age and sex-adjusted Cox-regression analyses were performed. RESULTS: After applying trial in- and exclusion criteria, 48% of UCC-SMART patients with type 2 diabetes and cardiovascular disease would have been eligible for DECLARE-TIMI 58, 35% for CANVAS, 29% for EMPA-REG OUTCOME and 21% for VERTIS-CV. Without the eligibility criteria of HbA1c, eligibility was 58-88%. For all trials the observed risk for cardiovascular events and all-cause mortality was similar in eligible and ineligible patients after adjustment for age and gender. CONCLUSION: A large proportion of patients with type 2 diabetes and cardiovascular disease in daily clinical practice would have been eligible for participation in the SGLT2i CVOTs. Trial eligible and ineligible patients have the same risk for MACE and all-cause mortality.

Patient Selection for Routine Troponin Monitoring After Noncardiac Surgery.

Background Myocardial infarction is an important complication after noncardiac surgery. Therefore, perioperative troponin surveillance is recommended for patients at risk. The aim of this study was to identify patients at high risk of perioperative myocardial infarction (POMI), in order to aid appropriate selection and to omit redundant laboratory measurements in patients at low risk. Methods and Results This observational cohort study included patients ≥60 years of age who underwent intermediate to high risk noncardiac surgery. Routine postoperative troponin I monitoring was performed. The primary outcome was POMI. Classification and regression tree analysis was used to identify patient groups with varying risks of POMI. In each subgroup, the number needed to screen to identify 1 patient with POMI was calculated. POMI occurred in 216 (4%) patients and other myocardial injury in 842 (15%) of the 5590 included patients. Classification and regression tree analysis divided patients into 14 subgroups in which the risk of POMI ranged from 1.7% to 42%. Using a risk of POMI ≥2% to select patients for routine troponin I monitoring, this monitoring would be advocated in patients ≥60 years of age undergoing emergency surgery, or those undergoing elective surgery with a Revised Cardiac Risk Index class >2 (ie >1 risk factor). The number needed to screen to detect a patient with POMI would be 14 (95% CI 14-14) and 26% of patients with POMI would be missed. Conclusions To improve selection of high-risk patients ≥60 years of age, routine postoperative troponin I monitoring could be considered in patients undergoing emergency surgery, or in patients undergoing elective surgery classified as having a revised cardiac risk index class >2.

Added value of cardiovascular calcifications for prediction of recurrent cardiovascular events and cardiovascular interventions in patients with established cardiovascular disease.

The purpose is to investigate the added prognostic value of coronary artery calcium (CAC), thoracic aortic calcium (TAC), and heart valve calcium scores for prediction of a combined endpoint of recurrent major cardiovascular events and cardiovascular interventions (MACE +) in patients with established cardiovascular disease (CVD). In total, 567 patients with established CVD enrolled in a substudy of the UCC-SMART cohort, entailing cardiovascular CT imaging and calcium scoring, were studied. Five Cox proportional hazards models for prediction of 4-year risk of MACE + were developed; traditional CVD risk predictors only (model I), with addition of CAC (model II), TAC (model III), heart valve calcium (model IV), and all calcium scores (model V). Bootstrapping was performed to account for optimism. During a median follow-up of 3.43 years (IQR 2.28-4.74) 77 events occurred (MACE+). Calibration of predicted versus observed 4-year risk for model I without calcium scores was good, and the c-statistic was 0.65 (95%CI 0.59-0.72). Calibration for models II-V was similar to model I, and c-statistics were 0.67, 0.65, 0.65, and 0.68 for model II, III, IV, and V, respectively. NRIs showed improvement in risk classification by model II (NRI 15.24% (95%CI 0.59-29.39)) and model V (NRI 20.00% (95%CI 5.59-34.92)), but no improvement for models III and IV. In patients with established CVD, addition of the CAC score improved performance of a risk prediction model with classical risk factors for the prediction of the combined endpoint MACE+ . Addition of the TAC or heart valve score did not improve risk predictions.

Applicability of Blood Pressure-Lowering Drug Trials to Real-World Patients With Cardiovascular Disease.

This study aimed to assess applicability of blood pressure-lowering drug trials to real-world secondary preventive care. We applied the eligibility criteria of the landmark blood pressure-lowering drug trials (EUROPA, PEACE, HOPE-peripheral arterial disease [PAD], PRoFESS, and PROGRESS) to patients with coronary artery disease (CAD; n=5155), peripheral arterial disease (PAD; n=1487), and cerebrovascular disease (n=2515) participating in the UCC-SMART cohort. Baseline differences according to trial eligibility were assessed. Differences in risk of all-cause mortality and a composite of cardiovascular death, myocardial infarction, and stroke (major adverse cardiovascular event) were calculated using Cox proportional hazard models, adjusted for age, sex, and cardiovascular risk factors. Seventy-five percent of UCC-SMART patients with CAD would have been eligible for EUROPA, 84% for PEACE, 59% of patients with PAD for HOPE-PAD, 17% of patients with cerebrovascular disease for PRoFESS, and 100% for PROGRESS. Eligible patients were older (average difference ranging 1.4-14.6 years across trials). Eligible patients with CAD were at lower risk of major adverse cardiovascular event after adjustment for age, sex, and cardiovascular risk factors in PEACE (hazard ratio, 0.65 [95% CI, 0.53-0.79]) and of mortality in both EUROPA (hazard ratio, 0.72 [95% CI, 0.62-0.82]) and PEACE (0.63 [95% CI, 0.51-0.78]). Adjusted mortality and major adverse cardiovascular event risks were not different between eligible and ineligible patients with PAD and cerebrovascular disease in HOPE-PAD, PRoFESS, and PROGRESS. The majority of real-world patients with CAD, PAD, or cerebrovascular disease would be eligible for landmark trials on blood pressure-lowering drugs. Patients with CAD ineligible for the EUROPA and PEACE trials are at higher adjusted mortality and major adverse cardiovascular event risks, which may limit applicability of their results to ineligible patients.

Evaluating a cardiovascular disease risk management care continuum within a learning healthcare system: a prospective cohort study.

BACKGROUND: Many patients now present with multimorbidity and chronicity of disease. This means that multidisciplinary management in a care continuum, integrating primary care and hospital care services, is needed to ensure high quality care. AIM: To evaluate cardiovascular risk management (CVRM) via linkage of health data sources, as an example of a multidisciplinary continuum within a learning healthcare system (LHS). DESIGN & SETTING: In this prospective cohort study, data were linked from the Utrecht Cardiovascular Cohort (UCC) to the Julius General Practitioners' Network (JGPN) database. UCC offers structured CVRM at referral to the University Medical Centre (UMC) Utrecht. JGPN consists of electronic health record (EHR) data from referring GPs. METHOD: The cardiovascular risk factors were extracted for each patient 13 months before referral (JGPN), at UCC inclusion, and during 12 months follow-up (JGPN). The following areas were assessed: registration of risk factors; detection of risk factor(s) requiring treatment at UCC; communication of risk factors and actionable suggestions from the specialist to the GP; and change of management during follow-up. RESULTS: In 52% of patients, ≥1 risk factors were registered (that is, extractable from structured fields within routine care health records) before UCC. In 12%-72% of patients, risk factor(s) existed that required (change or start of) treatment at UCC inclusion. Specialist communication included the complete risk profile in 67% of letters, but lacked actionable suggestions in 86%. In 29% of patients, at least one risk factor was registered after UCC. Change in management in GP records was seen in 21%-58% of them. CONCLUSION: Evaluation of a multidisciplinary LHS is possible via linkage of health data sources. Efforts have to be made to improve registration in primary care, as well as communication on findings and actionable suggestions for follow-up to bridge the gap in the CVRM continuum.

Low-Density Lipoprotein Cholesterol Target Attainment in Patients With Established Cardiovascular Disease: Analysis of Routine Care Data.

BACKGROUND: Direct feedback on quality of care is one of the key features of a learning health care system (LHS), enabling health care professionals to improve upon the routine clinical care of their patients during practice. OBJECTIVE: This study aimed to evaluate the potential of routine care data extracted from electronic health records (EHRs) in order to obtain reliable information on low-density lipoprotein cholesterol (LDL-c) management in cardiovascular disease (CVD) patients referred to a tertiary care center. METHODS: We extracted all LDL-c measurements from the EHRs of patients with a history of CVD referred to the University Medical Center Utrecht. We assessed LDL-c target attainment at the time of referral and per year. In patients with multiple measurements, we analyzed LDL-c trajectories, truncated at 6 follow-up measurements. Lastly, we performed a logistic regression analysis to investigate factors associated with improvement of LDL-c at the next measurement. RESULTS: Between February 2003 and December 2017, 250,749 LDL-c measurements were taken from 95,795 patients, of whom 23,932 had a history of CVD. At the time of referral, 51% of patients had not reached their LDL-c target. A large proportion of patients (55%) had no follow-up LDL-c measurements. Most of the patients with repeated measurements showed no change in LDL-c levels over time: the transition probability to remain in the same category was up to 0.84. Sequence clustering analysis showed more women (odds ratio 1.18, 95% CI 1.07-1.10) in the cluster with both most measurements off target and the most LDL-c measurements furthest from the target. Timing of drug prescription was difficult to determine from our data, limiting the interpretation of results regarding medication management. CONCLUSIONS: Routine care data can be used to provide feedback on quality of care, such as LDL-c target attainment. These routine care data show high off-target prevalence and little change in LDL-c over time. Registrations of diagnosis; follow-up trajectory, including primary and secondary care; and medication use need to be improved in order to enhance usability of the EHR system for adequate feedback.

Multifocal cardiovascular calcification in patients with established cardiovascular disease; prevalence, risk factors, and relation with recurrent cardiovascular disease.

AIMS: The aim is to investigate (multifocal) cardiovascular calcification in patients with established cardiovascular disease (CVD), regarding prevalence, risk factors, and relation with recurrent CVD or vascular interventions. Coronary artery calcification (CAC), thoracic aortic calcification (TAC) (including ascending aorta, aortic arch, descending aorta), mitral annular calcification (MAC), and aortic valve calcification (AVC) are studied. METHODS: The study concerned 568 patients with established CVD enrolled in the ORACLE cohort. All patients underwent computed tomography. Prevalence of site-specific and multifocal calcification was determined. Ordinal regression analyses were performed to quantify associations of risk factors with cardiovascular calcification, and Cox regression analyses to determine the relation between calcium scores and recurrent CVD or vascular interventions. RESULTS: Calcification was multifocal in 76% (N = 380) of patients with calcification. Age (per SD) was associated with calcification at all locations (lowest OR 2.17; 99%CI 1.54-3.11 for ascending aorta calcification). Diabetes mellitus and systolic blood pressure were associated with TAC, whereas male sex was a determinant of CAC. TAC and CAC were related to the combined endpoint CVD or vascular intervention (N = 68). In a model with all calcium scores combined, only CAC was related to the combined outcome (HR 1.39; 95%CI 1.15-1.68). CONCLUSION: Cardiovascular calcification is generally multifocal in patients with established CVD. Differences in associations between risk factors and calcification at various anatomical locations stress the divergence in pathophysiological pathways. CAC is most strongly related to recurrent CVD or vascular interventions independent of traditional risk factors, and independent of heart valve and thoracic aorta calcification.

Apparent therapy-resistant hypertension as risk factor for the development of type 2 diabetes mellitus.

OBJECTIVE: To evaluate whether the relationship between hypertension and type 2 diabetes mellitus (T2DM) is different for patients with uncontrolled hypertension, controlled hypertension or patients with apparent therapy-resistant hypertension (aTRH), compared with patients without hypertension. METHODS: Using Cox proportional hazard models we evaluated the risk of new-onset T2DM in 8756 patients, at high risk for vascular disease. Hypertensive patients were subdivided according to blood pressure (BP) and use of BP-lowering drugs. BP ≥ 140/90 mmHg was defined as uncontrolled BP. aTRH was defined as uncontrolled BP despite being treated with at least three BP-lowering drugs including a diuretic, or the use at least four BP-lowering drugs irrespective of BP levels. Further analysis evaluated the risk of new-onset T2DM for patients with uncontrolled hypertension and for patients with aTRH, compared with patients with controlled hypertension and without hypertension, respectively. RESULTS: Forty-five percent had controlled hypertension, 20% had uncontrolled hypertension, 5.7% had aTRH, and 29% were nonhypertensive. During a follow-up of 7.0 (interquartile range: 0-14) years there were 705 new cases of T2DM. Patients with hypertension had a 1.48 (95% confidence interval 1.22-1.80) times higher risk of new-onset T2DM than nonhypertensive patients. There was no significant difference in risk among different hypertension groups. CONCLUSION: Patients at high risk for cardiovascular disease with hypertension have a 1.48 times higher risk of new-onset T2DM than nonhypertensive counterparts. The risk did not differ between patients with controlled hypertension, uncontrolled hypertension, or aTRH.