Abstract 219: Use of Machine Learning Models to Identify Atherosclerotic Cardiovascular Disease Patients at Very High Risk for Future Events in a Multi-state Health Care System

Background: In the 2018 AHA/ACC Blood Cholesterol Guideline, it is recommended that ASCVD patients be classified as very high-risk (VHR) vs not-VHR (NVHR) to guide treatment decisions. This has important implications for ezetimibe and PCSK9 inhibitor eligibility. We aimed to develop a tool that could assist in more easily identifying VHR patients based on machine learning (ML) techniques. This approach offers a powerful, assumption-free alternative to conventional methods, such as logistic regression, to identify potential interactions among risk factors while incorporating the hierarchy of interaction among variables. Method: We used EHR-derived ICD-10 codes to identify patients within our health system with ASCVD. VHR was defined by ≥2 major ASCVD events (ACS ≤12 months, history of MI \u3e12 months, ischemic stroke, or symptomatic PAD) or 1 major ASCVD event and ≥2 high-risk conditions (age ≥65, diabetes, hypertension, smoking, heterozygous familial hypercholesterolemia, CKD, CHF, persistently elevated LDL-C ≥100 mg/dl, or prior CABG/PCI). Patients not meeting these criteria were classified as NVHR. We randomly assigned patients into a training set and a testing set. Classification and regression tree (CART) modeling was performed on the training set and validated on the testing set. The results were compared with a random forest model. Variables in both models included age, sex, race, ethnicity, and each of the VHR criteria above. The primary outcome for both models was VHR classification. Performance of the two models were compared using area under the curve (AUC). Result: A total of 180,669 ASCVD patients were identified in 2018: 104,123 (58%) were VHR and 76,546 (42%) were NVHR. Mean age and sex were 73.1±11.9 years, 55% male and 70.1±13.4 years, 54% male for the VHR and NVHR groups, respectively. Half the population was randomly selected as the training dataset (n=90,334) and the other half was used as the testing dataset (n=90,335). Both CART and random forest models identified recent ACS, ischemic stroke, hypertension, PAD, and history of MI as the top five predictors of VHR status. Ninety-six percent of patients with recent ACS were classified as VHR. Among patients with no recent ACS, 95% were classified as VHR if they had a stroke and hypertension. Among patients with no ACS or stroke, 89% were classified as VHR if they had PAD. Finally, among patients with no ACS, stroke or PAD, 90% were classified as VHR if they had a history of MI. The misclassification rate of the CART model on the testing set was 4.3%. The AUC for the CART and random forest models was 0.949 and 0.968, respectively. Conclusion: Both ML methods were highly predictive of VHR status among those with ASCVD. Use of this approach affords a simplified means to drive clinical decision making at the point of care

Burden of chronic kidney disease in the general population and high-risk groups in South Asia: A systematic review and meta-analysis

BACKGROUND: Chronic kidney disease (CKD) is an emerging public health issue globally. The prevalence estimates on CKD in South Asia are however limited. This study aimed to examine the prevalence of CKD among the general and high-risk population in South Asia. METHODS: We conducted a systematic review and meta-analysis of population-level prevalence studies in South Asia (Afghanistan, Bangladesh, Bhutan, Maldives, Nepal, India, Pakistan, and Sri Lanka). Three databases namely PubMed, Scopus and Web of Science were systematically searched for published reports of kidney disease in South Asia up to 28 October 2020. A random-effect model for computing the pooled prevalence was used. RESULTS: Of the 8749 identified studies, a total of 24 studies were included in the review. The pooled prevalence of CKD among the general population was 14% (95% CI 11-18%), and 15% (95% CI 11-20%) among adult males and 13% (95% CI 10-17%) in adult females. The prevalence of CKD was 27% (95% CI 20-35%) in adults with hypertension, 31% (95% CI 22-41%) in adults with diabetes and 14% (95% CI 10-19%) in adults who were overweight/obese. We found substantial heterogeneity across the included studies in the pooled estimates for CKD prevalence in both general and high-risk populations. The prevalence of CKD of unknown origin in the endemic population was 8% (95% CI 3-16%). CONCLUSION: Our study reaffirms the previous reports that CKD represents a serious public health challenge in South Asia, with the disease prevalent among 1 in 7 adults in South Asian countries

Relations between lipoprotein(a) concentrations, LPA genetic variants, and the risk of mortality in patients with established coronary heart disease: a molecular and genetic association study

BACKGROUND: Lipoprotein(a) concentrations in plasma are associated with cardiovascular risk in the general population. Whether lipoprotein(a) concentrations or LPA genetic variants predict long-term mortality in patients with established coronary heart disease remains less clear. METHODS: We obtained data from 3313 patients with established coronary heart disease in the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. We tested associations of tertiles of lipoprotein(a) concentration in plasma and two LPA single-nucleotide polymorphisms ([SNPs] rs10455872 and rs3798220) with all-cause mortality and cardiovascular mortality by Cox regression analysis and with severity of disease by generalised linear modelling, with and without adjustment for age, sex, diabetes diagnosis, systolic blood pressure, BMI, smoking status, estimated glomerular filtration rate, LDL-cholesterol concentration, and use of lipid-lowering therapy. Results for plasma lipoprotein(a) concentrations were validated in five independent studies involving 10 195 patients with established coronary heart disease. Results for genetic associations were replicated through large-scale collaborative analysis in the GENIUS-CHD consortium, comprising 106 353 patients with established coronary heart disease and 19 332 deaths in 22 studies or cohorts. FINDINGS: The median follow-up was 9·9 years. Increased severity of coronary heart disease was associated with lipoprotein(a) concentrations in plasma in the highest tertile (adjusted hazard radio [HR] 1·44, 95% CI 1·14-1·83) and the presence of either LPA SNP (1·88, 1·40-2·53). No associations were found in LURIC with all-cause mortality (highest tertile of lipoprotein(a) concentration in plasma 0·95, 0·81-1·11 and either LPA SNP 1·10, 0·92-1·31) or cardiovascular mortality (0·99, 0·81-1·2 and 1·13, 0·90-1·40, respectively) or in the validation studies. INTERPRETATION: In patients with prevalent coronary heart disease, lipoprotein(a) concentrations and genetic variants showed no associations with mortality. We conclude that these variables are not useful risk factors to measure to predict progression to death after coronary heart disease is established. FUNDING: Seventh Framework Programme for Research and Technical Development (AtheroRemo and RiskyCAD), INTERREG IV Oberrhein Programme, Deutsche Nierenstiftung, Else-Kroener Fresenius Foundation, Deutsche Stiftung für Herzforschung, Deutsche Forschungsgemeinschaft, Saarland University, German Federal Ministry of Education and Research, Willy Robert Pitzer Foundation, and Waldburg-Zeil Clinics Isny

Association of reproductive factors with dementia: a systematic review and dose-response meta-analyses of observational studies

Background: Associations between endogenous estrogen exposure indicators and risk of subtypes of dementia have been unclear. Methods: Databases (PubMed, EMBASE and Web of Science) were searched electronically on 1st July and updated regularly until 12nd November 2021. Observational studies of English language were selected if reported an effect estimate [e.g., odds ratio (OR), rate ratio (RR) or hazard ratio (HR)] and 95% CI for the association between any exposure (age of menarche, age at menopause, reproductive period, estradiol level) and any endpoint variable [all-cause dementia, Alzheimer's disease (AD), vascular dementia (VD), cognitive impairment (CI)]. Random-effects models and dose-response meta-analyses were used to calculate estimates and to show the linear/nonlinear relationship. PROSPERO CRD42021274827. Findings: We included 22 studies (475 9764 women) in this analysis. We found no clear relationship between late menarche (≥14 vs <14 years) and dementia, CI in categorical meta-analysis compared to a J-shape relationship in dose-response meta-analyses. Later menopause (≥45 vs <45 years) was consistently associated with a lower risk of all-cause dementia (pooled RR: 0.87, 95%CI: 0.78–0.97, I2=56.0%), AD (0.67, 0.44–0.99, I2=78.3%), VD (0.87, 0.80–0.94) and CI (0.82, 0.71–0.94, I2=19.3%) in categorical meta-analysis, showing similar results in dose-response meta-analyses. An inverse relationship between longer reproductive duration (≥35 vs <35 years) and dementia was observed in dose-response meta-analysis. In addition, estradiol levels after menopause were inversely correlated with the risk of AD and CI. Interpretation: In this study, later menopause and longer reproductive period were associated with a lower risk of dementia, while the relationship for menarchal age was J-shaped. There was an inverse relationship between higher postmenopausal estrogen levels and risk of AD and CI. Longitudinal study are needed to further explore the association between life-time estrogen exposure and risk of subtypes of dementia. Funding: Start-up Foundation for Scientific Research in Shandong University

Trend, predictors, and outcomes of combined mitral valve replacement and coronary artery bypass graft in patients with concomitant mitral valve and coronary artery disease: a National Inpatient Sample database analysis.

Aims: Combined mitral valve replacement (MVR) and coronary artery bypass graft (CABG) procedures have been the norm for patients with concomitant mitral valve disease (MVD) and coronary artery disease (CAD) with no large-scale data on their safety and efficacy. Methods and results: The National Inpatient Sample database (2002-18) was queried to identify patients undergoing MVR and CABG. The major adverse cardiovascular events (MACE) and its components were compared using a propensity score-matched (PSM) analysis to calculate adjusted odds ratios (OR). A total of 6 145 694 patients (CABG only 3 971 045, MVR only 1 933 459, MVR + CABG 241 190) were included in crude analysis, while a matched cohort of 724 237 (CABG only 241 436, MVR only 241 611 vs. MVR + CABG 241 190) was selected in PSM analysis. The combined MVR + CABG procedure had significantly higher adjusted odds of MACE [OR 1.13, 95% confidence interval (CI) 1.11-1.14 and OR 1.96, 95% CI 1.93-1.99] and in-hospital mortality (OR 1.29, 95% CI 1.27-1.31 and OR 2.1, 95% CI 2.05-2.14) compared with CABG alone and MVR alone, respectively. Similarly, the risk of post-procedure bleeding, major bleeding, acute kidney injury, cardiogenic shock, sepsis, need for intra-aortic balloon pump, mean length of stay, and total charges per hospitalization were significantly higher for patients undergoing the combined procedure. These findings remained consistent on yearly trend analysis favouring the isolated CABG and MVR groups. Conclusion: Combined procedure (MVR + CABG) in patients with MVD and CAD appears to be associated with worse in-hospital outcomes, increased mortality, and higher resource utilization compared with isolated CABG and MVR procedures. Randomized controlled trials are needed to determine the relative safety of these procedures in the full spectrum of baseline valvular and angiographic characteristics

Prognostic model to predict postoperative acute kidney injury in patients undergoing major gastrointestinal surgery based on a national prospective observational cohort study.

Background: Acute illness, existing co-morbidities and surgical stress response can all contribute to postoperative acute kidney injury (AKI) in patients undergoing major gastrointestinal surgery. The aim of this study was prospectively to develop a pragmatic prognostic model to stratify patients according to risk of developing AKI after major gastrointestinal surgery. Methods: This prospective multicentre cohort study included consecutive adults undergoing elective or emergency gastrointestinal resection, liver resection or stoma reversal in 2-week blocks over a continuous 3-month period. The primary outcome was the rate of AKI within 7 days of surgery. Bootstrap stability was used to select clinically plausible risk factors into the model. Internal model validation was carried out by bootstrap validation. Results: A total of 4544 patients were included across 173 centres in the UK and Ireland. The overall rate of AKI was 14·2 per cent (646 of 4544) and the 30-day mortality rate was 1·8 per cent (84 of 4544). Stage 1 AKI was significantly associated with 30-day mortality (unadjusted odds ratio 7·61, 95 per cent c.i. 4·49 to 12·90; P < 0·001), with increasing odds of death with each AKI stage. Six variables were selected for inclusion in the prognostic model: age, sex, ASA grade, preoperative estimated glomerular filtration rate, planned open surgery and preoperative use of either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker. Internal validation demonstrated good model discrimination (c-statistic 0·65). Discussion: Following major gastrointestinal surgery, AKI occurred in one in seven patients. This preoperative prognostic model identified patients at high risk of postoperative AKI. Validation in an independent data set is required to ensure generalizability

Mid-term outcomes for Endoscopic versus Open Vein Harvest: a case control study

<p>Abstract</p> <p>Background</p> <p>Saphenous vein remains the most common conduit for coronary artery bypass grafting with increasing uptake of minimally invasive harvesting techniques. While Endoscopic Vein Harvest (EVH) has been demonstrated to improve early morbidity compared to Open Vein Harvest (OVH), recent literature suggests that this may be at the expense of graft patency at one year and survival at three years.</p> <p>Methods</p> <p>We undertook a retrospective single-centre, single-surgeon, case-control study of EVH (n = 89) and OVH (n = 182). The primary endpoint was death with secondary endpoints including acute coronary syndrome, revascularisation or other major adverse cardiac events. Freedom from angina, wound complications and self-rated health status were also assessed. Where repeat angiography had been performed, this was reviewed.</p> <p>Results</p> <p>Both groups were well matched demographically and for peri-operative characteristics. All cause mortality was 2/89 (2%) and 11/182 (6%) in the EVH and OVH groups respectively. This was shown by Cox Log-Rank analysis to be non-significant (p = 0.65), even if adjusting for inpatient mortality (p = 0.74). There was no difference in the rates of freedom from angina (p = 1.00), re-admission (p = 0.78) or need for further anti-anginals (p = 1.00). There was a significant reduction in the incidence of leg wound infections and complications in the endoscopic group (EVH: 7%; OVH: 28%; p = 0.0008) and the skew of high patient self-rated health scores in the EVH group (61% compared to 52% in the open group) approached statistical significance (p = 0.06).</p> <p>Conclusions</p> <p>While aware of the limitations of this small retrospective study, we are heartened by the preliminary results and consider our data to be justification for continuing to provide patients the opportunity to have minimally invasive conduit harvest in our centre. More robust evidence is still required to elucidate the implications of endoscopic techniques on conduit patency and patient outcome, but until the results of a large, prospective and randomised trial are available, we believe we can confidently offer our patients the option and benefits of EVH.</p