Improving Familial Hypercholesterolemia Diagnosis Using an EMR-based Hybrid Diagnostic Model

Background Familial hypercholesterolemia (FH) confers a greatly increased risk for premature cardiovascular disease (CVD), but remains very under-diagnosed and under-treated in primary care populations. We assessed whether using a hybrid model consisting of two existing FH diagnostic criteria coupled with electronic medical record (EMR) data, would accurately identify patients with FH in a midwest US metropolitan healthcare system. Methods and Results We conducted a retrospective, records-based, cross-sectional study using datasets from unique EMRs of living patients. Using Structured Query Language (SQL) to identify components of two currently approved FH diagnostic criteria, we created a hybrid model to identify individuals with FH. Of 264 264 records analyzed, between 794 and 1571 patients were identified as having FH based on the hybrid diagnostic model, with a prevalence of 1:300 to 1:160. These patients had a higher prevalence of premature coronary artery disease (CAD) (38%-58%) compared with the general population (1.8%) and compared with those having a high CAD risk, but no FH (10%). Although most patients were receiving lipid-lowering therapies (LLT), only 50% were receiving guideline-recommended high-intensity LLT. Conclusion Using the hybrid model, we identified FH with a higher clinical and genetic detection rate compared with using standard diagnostic criteria, individually. Statin and other LLT use were suboptimal and below guideline recommendations. Because FH under-diagnosis and under-treatment are due partially to the challenges of implementing existing diagnostic criteria in a primary care setting, this hybrid model potentially can improve FH diagnosis and subsequent early access to appropriate treatment.

Risk factors for premature coronary artery disease (PCAD) in adults: a systematic review protocol

PCAD possesses a public health challenge resulting in years of productive life lost and an escalating burden on health systems. Objective of this review is to compare modifiable and non-modifiable risk factors for PCAD compared to those without PCAD. This review will include all comparative observational studies conducted in adults aged >18 years with confirmed diagnosis of PCAD (on angiography) compared to those without PCAD. Databases to be searched include; PubMed, CINAHL, Embase, Web of Science, and grey literature (Google Scholar). All identified studies will be screened for title and abstract and full-text against the inclusion criteria on Covidence software. Data relevant to exposures and outcomes will be extracted from all included studies. All studies selected for data extraction will be critically appraised for methodological quality. Meta-analysis using random-effects model will be performed using Review Manager 5.3. Effect sizes for categorical risk factors will be expressed as odds ratios with 95% confidence intervals. For risk factors measured in continuous form, mean difference (if units are consistent) otherwise standardized mean difference (if units are different across studies) will be reported. Heterogeneity between studies will be assessed using I2 test statistics. GRADE will be used to assess the certainty of the findings. Systematic review registration number: PROSPERO Registration # CRD42020173216

Premature Coronary Artery Disease Is More Prevalent in People Who Go to Bed Late

Background: Little is known regarding the impact of quantity and quality of sleep on the incidence of cardiovascular disease. The aim of this study was to investigate the possible independent association of late bedtime and premature coronary artery disease (PCAD). Methods: Between October 2016 and November 2019, we conducted a cross-sectional population-based study on 30101 participants aged 20–65 years in Khuzestan Comprehensive Health Study (KCHS). Data on major risk factors of cardiovascular disease, habit history, physical activity, and sleep behavior was gathered and participants underwent blood pressure, anthropometric, and serum lipid and glucose profile measurements. PCAD was defined as documented history of developing obstructive coronary artery disease before 45 years in men and before 55 years in women. Results: Of a total of 30101 participants (64.1% female, mean age: 41.7±11.7 years) included in this study, 1602 (5.3%, 95% confidence interval: 5.1%–5.6%) had PCAD. Late bedtime was reported in 7613 participants (25.3%, 95% confidence interval: 24.9%–25.8%). Age-sex standardized prevalence for PCAD and late bedtime were 3.62 (3.43-3.82) and 27.8 (27.2–28.4), respectively. There was no significant difference (P=0.558) regarding prevalence of PCAD between those with late bedtime (5.5%, 95% CI: 4.9%–6.0%) and those with early bedtime (5.3%, 95% CI: 5.0%–5.6%). However, after adjustment for potential confounders, late bedtime was independently associated with PCAD (OR=1.136, 95% CI=1.002–1.288, P=0.046). Conclusion: In this study, late bedtime was significantly associated with presence of PCAD. Future prospective studies should elucidate the exact role of late bedtime in developing coronary atherosclerosis prematurely.

Abstract 17234: Cisplatin Induced Coronary Artery Atherosclerosis Leading To St-elevation Myocardial Infarction: A Case Report

Introduction: Cisplatin-based chemotherapeutic regimen (CBCR) is known for increasing risk of venous thromboembolic (TE) disease. We report a unique case of STEMI associated with CBCR which we believe was caused by coronary artery thrombosis. Case description: A 31-yo man with a past history of germ cell tumor presented with chest pain radiating to back and left arm. It started this morning and intensity did not worsen with exertion. He denied any dyspnea, diaphoresis or palpitations. He was non-smoker and non-obese. He denied any family history of premature coronary artery disease. He had undergone unilateral orchiectomy a year ago, and was currently receiving chemotherapy with bleomycin, etoposide and cisplatin; the last dose of his 3 rd cycle was given the day before. EKG showed ST elevation in leads I, aVL, V4 and V5. Troponin I was high to 6.9 ng/ml (ULN 0.045 ng/ml). He received intravenous infusion of thrombolytic. An angiogram done the next day showed moderate mid-LAD disease with residual clot. A CT scan and an echocardiogram later showed left ventricular thrombus (LVT). He was kept on therapeutic enoxaparin along with aspirin. Follow up echocardiogram showed resolution of the thrombus. His chemotherapy was stopped, and he has been kept on active surveillance since then. Discussion: Most cases of CBCR-associated myocardial infarction that have been reported have been seen in the older population with other risk factors for coronary artery disease. Cases where angiographic data was available, coronary artery vasospasm appeared to be the culprit rather than a true plaque rupture. While the presence of LVT raises possibility of thromboembolism to coronaries causing MI, the angiographic findings support accelerated plaque formation to be the cause of infarction. In earlier reports, elevated pre-treatment level of von Willebrand factor has been postulated to have some role in the disease pathogenesis. Other possible mechanisms for pathogenesis include endothelial cell damage, platelet activation, and imbalance between thromboxane-prostacyclin levels. This case emphasizes the need to keep cardiac etiologies of chest pain in the differential when evaluating patients on CBCR as timely intervention is life saving and prevent morbidity.

Impact of Pre-existing Cardiovascular Disease and Risk Factors for Cardiovascular Disease in Pregnancy on Maternal Mortality

BackgroundCardiovascular disease (CVD) and risk factors for CVD are important indirect causes of maternal mortality in lower-middle-income countries (LMIC). The purpose of this research was to assess the prevalence of pre-existing CVD and risk factors for CVD in pregnant women and their relationship to maternal mortality in LMIC.ResultsThis was a cross-sectional study conducted on 3190 pregnant patients with pre-existing CVD and risk factors for CVD from 1st January 2018 through 31st December 2020 at a tertiary care hospital of Pakistan-a LMIC. A two-tailed Mann-Whitney two-sample rank-sum test, fisher’s exact test, and binary logistic regression were used for statistical analysis.Of 3190 patients, 517 (16.21%) individuals had risk factors for CVD, whereas 533 had pre-existing CVD (16.71 %). Diabetes mellitus type II was the most common risk factor for CVD, accounting for 238 (7.46 %) of all patients, followed by dyslipidemia in 162 (5.08 %), obesity in 153 (4.8 %), chronic hypertension in 151 (4.73 %), and family history (FH) of premature coronary artery disease (CAD) in 56 (1.76 %). Among patients with pre-existing CVD, 197 (6.18%) had ischemic heart disease (IHD), 182 (5.71%) had valvular heart disease (VHD), and 146 (4.58%) had cardiomyopathy. In this study majority of maternal deaths occurred in patients with diabetes (128(54%), p<.001) and ischemic heart disease (87(37%), p<.001). A one-unit rise in BMI increased maternal mortality by 13%. In contrast, the absence of Pre-existing CVD and risk factors for CVD conferred a protective effect from the adverse outcome i.e. maternal death. Maternal mortality was reduced by 66% in normoglycemic pregnant patients, 47% in patients without chronic HTN, 90% in patients without valvular heart disease, 97% without ischemic heart disease, and 99% without cardiomyopathy.ConclusionCVD and risk factors for CVD are major determinants of maternal mortality in pregnancy. Identifying such patients is imperative so that prompt measures can be taken beforehand to prevent adverse outcomes.

Gender Differences in South Indians with Premature Coronary Artery Disease (< 40 Years)—Insights from the PCAD Registry

Introduction Coronary artery disease (CAD) follows a different pattern in women and men, more so in the young (< 40 years). The gender differences in the risk factors, clinical presentation and diagnosis need to be understood, so that appropriate and timely treatment can be given. Objective The study contemplates to analyze the gender differences in the presence of major coronary risk factors, clinical presentation, diagnosis and immediate outcomes in patients who present with premature CAD (PCAD). Patients and Methods We evaluated 1,062 consecutive registry patients who presented with diagnosis of PCAD between 2018 to 2019 at our institution after satisfying the inclusion criteria. Results The study analyses 82 females and 980 males. The mean age of females was 35.4 ± 4.68 years and males was 34.2 ± 4.25 years. Males smoked more often (55.1%, p < 0.001). Females more often had abnormal BMI (84.1%, p < 0.001), increased waist-hip ratios (97.6%, p < 0.001), diabetes (35.4%, p < 0.001), dyslipidemia (17.1% vs. 11%) and hypertension (15.9% vs. 11.5%). STEMI was the most common presentation among males (80.4% vs. 71.9%). Majority of females (74.6%) presented 6 hours after index pain. NSTEMI was more common among females (20.7% vs. 16%). Single-vessel involvement was common in both sexes (84.1% in males and 85.2% in females). Obstructive CAD was less common in both groups. Conclusions Conventional risk factors play a major role for CAD in Indians. Smoking was common in males and metabolic syndrome in females. Also, females had a higher threshold for seeking treatment and referral. Measures have to be taken for early diagnosis and referral of females. Recanalized and thrombotic coronaries were common, indicating predominant thrombus burden in the young

Serum Free Fatty Acids were Associated with Acute Coronary Syndrome and Complexity of Coronary Artery Disease in Premature Coronary Artery Disease Patients

Background: With the rapid change of lifestyle, the incidence of coronary artery disease (CAD) was gradually rising among young people, but the specific reason for it was unclear. There were many evidences suggesting free fatty acids (FFAs) were involved in progression of CAD, our study was designed to discuss the relationship between serum FFAs and acute coronary syndrome (ACS) and the complexity of coronary artery disease in premature coronary artery disease (pCAD) patients. Methods: 502 pCAD patients suffering from ACS confirmed by coronary angiography in Beijing Anzhen Hospital from January to December 2019 were enrolled (ACS group), and 141 patients of the same age whose coronary angiography result was negative were selected during the same period (control group). The clinical data and characteristics of CAD among two groups were gathered and compared.Results: The level of FFAs in ACS group was significantly higher than control group (P < 0.001), and the value of FFAs in AMI group was higher than UA (P < 0.05) in both genders. The concentration of FFAs in three-vessel disease group was higher than double-vessel disease group and double-vessel disease group was higher than single-vessel disease group. The linear correlation coefficient between FFAs value and SYNTAX score was 0.370, P < 0.001. The AUC of FFAs to diagnose ACS was 0.798 (0.743-0.853, P < 0.001) in males, and 0.738 (0.677-0.800, P < 0.001) in females. Logistic regression analysis showed that elevated level of FFAs [odds ratio (OR) = 7.06, 95% confidence interval (CI) 4.40-11.33, P < 0.001] was independently associated with ACS. Conclusions: Concentration of FFAs is an independent risk factor associated with the incidence of ACS in pCAD patients and positively correlated with the complexity of CAD.