Premature Coronary Heart Disease Research Articles

Influencing Factors and Survival Analysis of Late Readmission after Percutaneous Coronary Intervention in Patients with Acute Myocardial Infarction

Objective: This study aimed to explore the influencing factors analysis of late readmission after patients with acute myocardial infarction received percutaneous coronary intervention (PCI). Methods: A total of 368 patients with acute myocardial infarction who received PCI treatment in West China Hospital, Sichuan University/West China School of Nursing, Sichuan University from January 2018, to January 2021, were selected for the study. Among them, 110 subjects were excluded, and 258 subjects were finally included, of which 124 were readmitted and 134 were not readmitted. The baseline data and clinical characteristics of the patients were collected, and the influencing factors of readmission were analyzed by logistic regression analysis. The readmitted patients were followed up for 12 months. The Kaplan–Meier method was used to analyze the survival of patients with delayed readmitted and calculate the survival rate. Results: Significant differences were found between readmitted patients and non-readmitted patients in terms of age, chronic obstructive pulmonary disease (COPD), history of early coronary heart disease, history of hypertension, history of oral anticoagulant drugs, and left ventricle ejection fraction (LVEF, p < 0.05). No significant differences were observed in gender, body mass index, family history of acute myocardial infarction, history of chronic kidney disease, history of diabetes, history of smoking, history of drinking, and the number of implanted stents and diseased vessels (p > 0.05). Binary logistic regression analysis showed that age, COPD, history of premature coronary heart disease, history of oral anticoagulant drugs, and LVEF were important influencing factors of delayed readmission after PCI (all p < 0.05). Follow-up results showed that 125 patients survived and nine died among the delayed non-readmission patients after PCI. Among the patients with delayed readmission, 95 survived and 29 died. Kaplan–Meier survival analysis showed that the survival time of patients with delayed non-readmission was longer than that of patients with delayed readmission, and the difference was statistically significant (χ2 = 17.696, p < 0.001). Conclusion: Age, COPD, history of oral anticoagulant drugs, and LVEF are important influencing factors of delayed readmission after PCI, and the survival time of patients with delayed non-readmission is longer than that of patients with delayed readmission.

Addressing comprehensive complexities a striking familial hypercholesterolemia case study.

Premature aortic involvement and comprehensive management strategies in familial hypercholesterolemia familial hypercholesterolemia (FH), a rare autosomal dominant genetic disorder, poses significant challenges due to its propensity for elevated low-density lipoprotein cholesterol, premature coronary heart disease, and vascular atherosclerosis. Unraveling Cardiovascular Complexities: A Striking Familial Hypercholesterolemia. This case study delves into a remarkable instance of FH in a 16-year-old female who presented with chest pain and worsening dyspnea. Diagnostic evaluation revealed distinct electrocardiographic changes, elevated troponin levels, and profound dyslipidemia. Remarkable findings on transthoracic echocardiography, computed tomography angiography, and catheterization prompted multidisciplinary interventions and demonstrated remarkable enhancements in ventricular function, mitral regurgitation, and aortic stenosis. The case study underscores the urgency of comprehensive management strategies in confronting the myriad challenges of FH, emphasizing the value of early intervention, innovative therapies, and rigorous imaging modalities for unraveling the intricate cardiovascular manifestations of this condition.

Plasma Biomarker Profiles for Premature and Nonpremature Coronary Heart Disease in Women.

Premature coronary heart disease (CHD) is a major cause of death in women. We aimed to characterize biomarker profiles of women who developed CHD before and after age 65 years. In the Women's Health Study (median follow-up 21.5 years), women were grouped by age and timing of incident CHD: baseline age <65 years with premature CHD by age 65 years (25 042 women; 447 events) and baseline age ≥65 years with nonpremature CHD (2982 women; 351 events). Associations of 44 baseline plasma biomarkers measured using standard assays and a nuclear magnetic resonance (NMR)-metabolomics assay were analyzed using Cox models adjusted for clinical risk factors. Twelve biomarkers showed associations only with premature CHD and included lipoprotein(a), which was associated with premature CHD [adjusted hazard ratio (HR) per SD: 1.29 (95% CI 1.17-1.42)] but not with nonpremature CHD [1.09(0.98-1.22)](Pinteraction = 0.02). NMR-measured lipoprotein insulin resistance was associated with the highest risk of premature CHD [1.92 (1.52-2.42)] but was not associated with nonpremature CHD (Pinteraction <0.001). Eleven biomarkers showed stronger associations with premature vs nonpremature CHD, including apolipoprotein B. Nine NMR biomarkers showed no association with premature or nonpremature CHD, whereas 12 biomarkers showed similar significant associations with premature and nonpremature CHD, respectively, including low-density lipoprotein (LDL) cholesterol [1.30(1.20-1.45) and 1.22(1.10-1.35)] and C-reactive protein [1.34(1.19-1.50) and 1.25(1.08-1.44)]. In women, a profile of 12 biomarkers was selectively associated with premature CHD, driven by lipoprotein(a) and insulin-resistant atherogenic dyslipoproteinemia. This has implications for the development of biomarker panels to screen for premature CHD.

Premature coronary heart disease complicated with hypertension in hospitalized patients: Incidence, risk factors, cardiovascular-related comorbidities and prognosis, 2008–2018

BackgroundThe clinical characteristics and risk factors of all-cause mortality in young hospitalized patients with comorbid coronary heart disease and hypertension (CAD + HT) are not well-characterized. MethodA total of 2288 hospitalized CAD patients (age<45 years) with or without hypertension in the Chinese PLA General Hospital from August 5, 2008 to June 22, 2018 were conducted. The risk factors of all-cause mortality were estimated in young CAD + HT patients by COX models. ResultsThe overall prevalence of hypertension in young CAD patients was 50.83% (n = 1163). CAD + HT patients had older age, higher heart rate, BMI, uric acid, triglyceride and lower level of eGFR and HDL-C than CAD patients (P < 0.05). The proportion of cardiovascular-related comorbidities (including obesity, diabetes mellitus, hyperuricemia and chronic kidney disease [CKD]) in the CAD + HT group was significantly higher than that in CAD group (P < 0.0001). The risk of all-cause mortality was higher in CAD + HT patients, although after adjusting for all covariates, there was no significant difference between the two groups. Furthermore, CKD (HR, 3.662; 95% CI, 1.545–8.682) and heart failure (HF) (HR, 3.136; 95%CI, 1.276–7.703) were associated with an increased risk of all-cause mortality and RAASi (HR, 0.378; 95%CI, 0.174–0.819) had a beneficial impact in CAD + HT patients. ConclusionsHypertension was highly prevalent in young CAD patients. Young CAD + HT patients had more cardiovascular metabolic risk factors, more cardiovascular-related comorbidities and higher risk of all-cause mortality. CKD and HF were the risk factors, while RAASi was a protective factor, of all-cause mortality in CAD + HT patients.

Doença coronariana em jovens: novas formas de detecção, prevenção e tratamento

In spite of major advancements in the management and prevention strategies of atherosclerosis, the prevalence of coronary artery disease has risen worldwide, and might start at an early age. Cardiovascular diseases among young adults are characterized as a heterogeneous group of disorders due to congenital or acquired causes. Multiple risk factors, such as dyslipidemia, premature coronary heart disease, diabetes mellitus and cigarette smoking potentiate the patient’s risk for early coronary heart disease. Early assessment of patients with coronary artery disease can be performed using various non-invasive imaging methods, which facilitate early selection of effective and preventative therapies for coronary artery disease management; however, it is associated with several challenges due to limitations in risk calculators, and limited sensitivity of various screening methods. In this manuscript, we will discuss about pathophysiology, risk factors, invasive and non- invasive imaging methods, and various management strategies for the early prevention of coronary heart disease in young adults and, importantly, the future directions and preventing disease and sudden cardiac death.

Familial Hypercholesterolemia Variant and Cardiovascular Risk in Individuals With Elevated Cholesterol

Familial hypercholesterolemia (FH) is a genetic disorder that often results in severely high low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). However, the impact of FH variants on CHD risk among individuals with moderately elevated LDL-C is not well quantified. To assess CHD risk associated with FH variants among individuals with moderately (130-189 mg/dL) and severely (≥190 mg/dL) elevated LDL-C and to quantify excess CHD deaths attributable to FH variants in US adults. A total of 21 426 individuals without preexisting CHD from 6 US cohort studies (Atherosclerosis Risk in Communities study, Coronary Artery Risk Development in Young Adults study, Cardiovascular Health Study, Framingham Heart Study Offspring cohort, Jackson Heart Study, and Multi-Ethnic Study of Atherosclerosis) were included, 63 of whom had an FH variant. Data were collected from 1971 to 2018, and the median (IQR) follow-up was 18 (13-28) years. Data were analyzed from March to May 2023. LDL-C, cumulative past LDL-C, FH variant status. Cox proportional hazards models estimated associations between FH variants and incident CHD. The Cardiovascular Disease Policy Model projected excess CHD deaths associated with FH variants in US adults. Of the 21 426 individuals without preexisting CHD (mean [SD] age 52.1 [15.5] years; 12 041 [56.2%] female), an FH variant was found in 22 individuals with moderately elevated LDL-C (0.3%) and in 33 individuals with severely elevated LDL-C (2.5%). The adjusted hazard ratios for incident CHD comparing those with and without FH variants were 2.9 (95% CI, 1.4-6.0) and 2.6 (95% CI, 1.4-4.9) among individuals with moderately and severely elevated LDL-C, respectively. The association between FH variants and CHD was slightly attenuated when further adjusting for baseline LDL-C level, whereas the association was no longer statistically significant after adjusting for cumulative past LDL-C exposure. Among US adults 20 years and older with no history of CHD and LDL-C 130 mg/dL or higher, more than 417 000 carry an FH variant and were projected to experience more than 12 000 excess CHD deaths in those with moderately elevated LDL-C and 15 000 in those with severely elevated LDL-C compared with individuals without an FH variant. In this pooled cohort study, the presence of FH variants was associated with a 2-fold higher CHD risk, even when LDL-C was only moderately elevated. The increased CHD risk appeared to be largely explained by the higher cumulative LDL-C exposure in individuals with an FH variant compared to those without. Further research is needed to assess the value of adding genetic testing to traditional phenotypic FH screening.

Genetic heterogeneity of familial hypercholesterolaemia in two populations from two different countries

BackgroundFamilial hypercholesterolemia (FH) is a genetically determined monogenic disorder of predominantly autosomal dominant inheritance. A number of studies on differences in the genetic profile of patients with FH have demonstrated the importance of a more substantive evaluation of genetic features. The aim of this study was to evaluate the genetic profile of patients with clinical FH among Italian and Russian patients. MethodsWe included 144 Italian and 79 Russian FH patients; clinical diagnosis was based on the same criteria. Patients were divided in: positive to genetic test (one causative variant), inconclusive (only variants of uncertain clinical significance [VUS]), and negative (with likely benign/benign variants, heterozygous variants in LDLRAP1 gene, or without causative variants). ResultsThe genetic test was positive in 76.4 % of the Italian patients and in 49.4 % of the Russian patients. The presence of VUS alone was detected in 7.6 % and in 19.0 % (p < 0.001), respectively. Among patients with positive genetic diagnosis, pre-treatment LDL-C levels were higher in the Russian cohort (353.5 ± 111.3 vs. 302.7 ± 52.1 mg/dL, p = 0.009), as well as the percentage of treated patients (53.8 % vs. 14.5 %, p < 0.001) and the prevalence of premature coronary heart disease (12.8 % vs. 3.6 %, p = 0.039). Among patients carrying only VUS, mean pre-treatment LDL-C levels were similar between the cohorts (299.5 ± 68.1 vs. 295.3 ± 46.8 mg/dL, p = 0.863). Among pathogenic/likely pathogenic variants and VUS, only 5 % and 4 % was shared between the two cohorts, respectively. ConclusionThe genetic background of patients clinically diagnosed with FH in two different countries is characterized by high variability.

The association between glycemic index, glycemic load and total carbohydrate intake and risk of premature coronary artery disease: Iran Premature Coronary Artery Disease Study (IPAD) - A Case-Control Study

Background and aimsThe association between glycemic index (GI), glycemic load (GL), total carbohydrate intake, and risk of cardiovascular diseases has been controversial. Premature coronary artery disease (PCAD) is characterized by the age of onset lower than 55 and 65 respectively in men and women. The aim of the current study is to investigate the relationship between GI, GL and carbohydrate levels and the risk of PCAD in Iran. Methods and resultsIn total, 419 healthy people and 553 patients struggling with PCAD have participated in this case-control study. Dietary GI and GL were calculated using a validated food frequency questionnaire at the baseline. Crude and multivariable logistic regression were used to assess the relationship between GI, GL, and total carbohydrate intake and risk of PCAD. The mean age of participants was 51.13 ± 6.90 and 46 % of them were women. A significant direct relationship was observed between higher carbohydrate intake (OR: 1.74, 95%CI: 1.27–2.38) and GL levels (OR: 1.56, 95 % CI:1.14–2.14) and risk of PCAD. These associations were not significant after adjusting for potential variables. No significant association has been observed between GI and odds of PCAD even after controlling for all covariates. ConclusionWe found no significant association between GI, GL, and total carbohydrate intake and risk of premature coronary heart disease. Further observational and clinical trials are required to assess this relationship.

The effect of LDL-C/HDL-C ratio on severity of coronary artery disease and 2-year long-term prognosis in patients with premature coronary heart disease---a multicenter, observational results

Abstract Background Low density lipoprotein cholesterol (LDL-C) level is a strong predictor of premature coronary heart disease（CHD）and a risk factor for poor prognosis. While high density lipoprotein cholesterol (HDL-C) is a protective factors for atherosclerosis. However, the relationship between the LDL/HDL ratio and the severity of coronary artery disease and the prognosis of patients with premature CHD is still unclear. Purpose To explore the effect of LDL-C/HDL-C ratio on the severity of coronary artery disease and 2-yeat long-term prognosis in patients with premature CHD. Methods This prospective, multicenter, observational cohort study is from the PROMISE study. 18701 patients with CHD were selected from January 2015 to May 2019. 3861 patients with premature CHD were enrolled in the current study. According to the median of LDL-C/HDL-C ratio (2.4), Patients were divided into two groups: low LDL-C/HDL-C group (LDL-C/HDL-C≤2.4, n=1867) and high LDL-C/HDL-C group (LDL-C/HDL-C&amp;gt;2.4, n=1994). Results Compared with the low LDL-C/HDL-C ratio group, the high LDL-C/HDL-C ratio group was younger. The levels of total cholesterol, triglyceride and LDL-C in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (3.67 ± 0.85 vs 4.91 ± 1.15; 1.66 ± 1.49 vs 2.22 ± 1.45; 2.0 ± 0.57 vs 3.22 ± 0.95, respectively, all p&amp;lt;0.001), and the HDL-C level was lower (1.17 ± 0.29 vs 0.96 ± 0.21, p&amp;lt;0.001). The number of target lesions, the number of coronary artery lesions, the preoperative SNYTAX score and the proportion of three-vessel coronary artery disease in the high LDL-C/HDL-C group were significantly higher than those in the low LDL-C/HDL-C group (0.97 ± 0.80 vs 1.04 ± 0.74, p=0.002; 1.85 ± 0.84 vs 2.04 ± 0.84, p&amp;lt;0.001; 11.70 ± 8.05 vs 13.81 ± 8.87, p&amp;lt;0.001; 27.4% vs 36.2%, respectively, p&amp;lt;0.001). Correlation analysis showed a significant positive correlation between LDL-C/HDL-C ratio and preoperative SYNTAX score, the number of coronary artery lesions, the number of target lesions and whether it was a three-vessel coronary artery disease (all p&amp;lt;0.05). The 2-year follow-up results showed that the incidence of MACCE in the high LDL-C/HDL-C group was significantly higher than low LDL-C/HDL-C group (6.9% vs 9.1%, p=0.011). COX multivariate regression analysis showed LDL-C/HDL-C ratio has no relationship with 2-year adverse events with patients with premature CHD. Conclusion (1) The patients with LDL-C/HDL-C ratio higher than 2.4 may suffer from atherosclerotic cardiovascular disease earlier; (2) High LDL-C/HDL-C ratio has significantly positive correlation with the severity of coronary artery disease in patients with premature CHD. The incidence of MACCE of patients with high LDL-C/HDL-C ratio was significantly higher in 2 years follow-up; (3) LDL-C/HDL-C ratio may be a better indicator for evaluating the severity of coronary artery disease and long-term prognosis in patients with premature CHD.Comparison of coronary artery disease2-year outcomes

Abstract 17155: Lipoprotein (a) Testing in an Academic Medical System

Introduction: Lp(a) is a causal risk factor for ASCVD that is often elevated in patients with personal or family history (FHx) of ASCVD. The 2019 ESC guidelines recommend universal Lp(a) testing, while the 2019 AHA/ACC guidelines include Lp(a) as a ‘risk enhancer’. We used electronic health records (EHR) to assess utilization of Lp(a) testing in patients with ASCVD, premature ASCVD, and FHx of ASCVD at Mayo Clinic sites in Rochester MN, Phoenix AZ and Jacksonville FL and the Mayo Clinic Health System (MCHS) from 1999-2021. Methods: We ascertained Lp(a) testing using LOINC codes and ASCVD status using validated ICD/CPT-based algorithms. ASCVD included coronary heart disease (CHD), cerebrovascular disease (CVD) (ischemic stroke and/or carotid artery stenosis), peripheral artery disease, and abdominal aortic aneurysm. Premature ASCVD was defined as occurring in males &lt; 55 years and females &lt; 65 years. We ascertained FHx using EHR survey data from 2017-2021. We estimated the proportion of patients with ASCVD, premature ASCVD, or FHx of ASCVD who underwent Lp(a) testing. Results: Between 1999-2021, we identified 310,760 patients with at least 1 ASCVD subtype of whom 66,710 had premature disease. FHx data was available starting 2017. For the timeframe 2017-2021, we identified 267,177 patients with FHx of ASCVD and 90,269 ASCVD patients. As summarized in Table 1, Lp(a) was tested only in a small proportion of patients; 7% of ASCVD patients, 11% of premature ASCVD patients, and 6% of patients with FHx of ASCVD. Premature CHD patients had the highest testing proportion (17%). Conclusions: Our results demonstrate underutilization of Lp(a) testing in patients with personal or FHx of ASCVD. Lp(a) is one of the mediators of “ASCVD residual risk” in patients on statins, and with new Lp(a)-lowering medications in phase III clinical trials, patient and provider education will be needed to increase awareness of Lp(a) as a modulator of ASCVD risk.

Comparison of the burden of familial hypercholesterolemia between two cohorts of French Canadians hospitalized 25 years apart for coronary heart disease

Familial hypercholesterolemia (FH) is associated with lifelong elevated plasma concentrations of low-density lipoprotein cholesterol (LDL-C) and high risk of premature coronary heart disease (CHD). Clinical recommendations and treatments have emerged to facilitate the management of FH patients. Their impact on the burden of FH is however not well documented. To compare the burden of FH between patients hospitalized for a CHD event 25 years apart in the French-Canadian founder population. Lipid profiles, cardiovascular risk factors, treatments and FH status of 2,029 patients consecutively hospitalized for an acute CHD event between 2017 and 2022 (2022 Cohort) were compared to those of 2,506 patients with angiographically-confirmed CHD who were admitted between 1995 and 1998 (1998 Cohort). At the time of admission, 24.6 % of CHD patients had LDL-C levels >5.0 mmol/L in 1998 compared to 1.4 % in 2022, and FH was diagnosed in 9.6 % of patients in the 1998 cohort compared to 5.5 % in 2022 (p<0.001). FH patients hospitalized for a CHD event were older in 2022 than in 1998 (p <0.001). The prevalence of premature CHD requiring a hospitalization significantly decreased from 1998 to 2022 (64.3% vs. 44.1 %, p<0.001). At the moment of admission, 18.2 % of FH patients had LDL-C concentration <2.0 mmol/L in 2022 vs 0 % in 1998 (p <0.001). Over 25 years, FH patients tend to be older and contribute to a lower proportion of hospitalizations for CHD in the French-Canadian founder population. Despite significant improvement in diagnosis and treatment, FH management remains however sub-optimal.

Specialty preference for cardiovascular prevention practice in the Southeast US and role of a preventive cardiologist.

Cardiovascular disease (CVD) prevention is practiced concurrently by providers from several specialties. Our goal was to understand providers' preference of specialties in CVD prevention practice and the role of preventive cardiologists. Between 11 October 2021 and 1 March 2022, we surveyed providers from internal medicine, family medicine, endocrinology, and cardiology specialties to examine their preference of specialties in managing various domains of CVD prevention. We examined categorical variables using Chi square test and continuous variables using t or analysis of variance test. Of 956 invitees, 263 from 21 health systems and 9 states responded. Majority of respondents were women (54.5%), practicing physicians (72.5%), specializing in cardiology (43.6%), and working at academic centers (51.3%). Respondents favored all specialties to prescribe statins (43.2%), ezetimibe (37.8%), sodium-glucose cotransporter-2 (SGLT2) inhibitors (30.5%), and aspirin in primary prevention (36.3%). Only 7.9% and 9.5% selected cardiologists and preventive cardiologists, respectively, to prescribe SGLT2 inhibitors. Most preferred specialists (i.e. cardiology and endocrinology) to manage advanced lipid disorders, refractory hypertension, and premature coronary heart disease. The most common conditions selected for preventive cardiologists to manage were genetic lipid disorders (17%), cardiovascular risk assessment (15%), dyslipidemia (13%), and refractory/resistant hypertension (12%). For CVD prevention practice, providers favored all specialties to manage common conditions, specialists to manage complex conditions, and preventive cardiologists to manage advanced lipid disorders. Cardiologists were least preferred to prescribe SGLT2 inhibitor. Future research should explore reasons for selected CVD prevention practice preferences to optimize care coordination and for effective use of limited expertise.

Lipoprotein(a) and Low-Molecular-Weight Apo(a) Phenotype as Determinants of New Cardiovascular Events in Patients with Premature Coronary Heart Disease.

Lipoprotein(a) (Lp(a)) is a genetic risk factor of atherosclerotic cardiovascular diseases (ASCVDs). Proprotein convertase subtilisin/kexin type 9 (PCSK9) is related to vascular inflammation and detected in atherosclerotic plaques. A temporary increase in the circulating concentration of PCSK9 and Lp(a) was shown in patients with myocardial infarction (MI). The aim of this study was to evaluate the role of the apo(a) phenotype and the Lp(a) concentration as well as its complex with PCSK9 in the development of cardiac events and MI in patients with a premature manifestation of coronary heart disease (CHD). In a prospective study with retrospective data collection, we included 116 patients with premature CHD who were followed for a median of 14 years. The medical history and information on cardiovascular events after an initial exam as well as data on the levels of lipids, Lp(a), PCSK9, PCSK9-Lp(a) complex, and apo(a) phenotype were obtained. The patients were divided into two groups depending on the presence of a low- (LMW, n = 52) or high-molecular weight (HMW, n = 64) apo(a) phenotype. LMW apo(a) phenotype (odds ratio 2.3 (1.1 to 4.8), p = 0.03), but not elevated Lp(a) (1.9 (0.8-4.6), p = 0.13), was an independent predictor for the development of MI after adjustment for sex, age of CHD debut, initial lipids levels, and lipid-lowering treatment. The apo(a) phenotype also determined the relationship between Lp(a) and PCSK9 concentrations. The level of the PCSK9-Lp(a) complex was higher in LMW apo(a) patients. The LMW apo(a) phenotype is a risk factor for non-fatal MI in a long-term prospective follow-up of patients with premature CHD, and this link could be mediated via PCSK9.

Prevalence of FH-Causing Variants and Impact on LDL-C Concentration in European, South Asian, and African Ancestry Groups of the UK Biobank-Brief Report.

Familial hypercholesterolemia (FH) is a monogenic disease that causes high low-density lipoprotein cholesterol (LDL-C) and higher risk of premature coronary heart disease. The prevalence of FH-causing variants and their association with LDL-C in non-European populations remains largely unknown. Using DNA diagnosis in a population-based cohort, we aimed to estimate the prevalence of FH across 3 major ancestry groups in the United Kingdom. Principal component analysis was used to distinguish genetic ancestry in UK Biobank participants. Whole exome sequencing data were analyzed to provide a genetic diagnosis of FH. LDL-C concentrations were adjusted for statin use. Principal component analysis distinguished 140 439 European, 4067 South Asian, and 3906 African participants with lipid and whole exome sequencing data. There were significant differences between the 3 groups, including total and LDL-C concentrations, and prevalence and incidence of coronary heart disease. We identified 488, 18, and 15 participants of European, South Asian, and African ancestry carrying a likely pathogenic or pathogenic FH-variant. No statistical difference in the prevalence of an FH-causing variant was observed: 1 out of 288 (95% CI, 1/316-1/264) in European, 1 out of 260 (95% CI, 1/526-1/173) in African, and 1 out of 226 (95% CI, 1/419-1/155) in South Asian. Carriers of an FH-causing variant had significantly higher LDL-C concentration than noncarriers in every ancestry group. There was no difference in median (statin-use adjusted) LDL-C concentration in FH-variant carriers depending on their ancestry background. Self-reported statin use was nonsignificantly highest in FH-variant carriers of South Asian ancestry (55.6%), followed by African (40.0%) and European (33.8%; P=0.15). The prevalence of FH-causing variants in the UK Biobank is similar across the ancestry groups analyzed. Despite overall differences in lipid concentrations, FH-variant carriers across the 3 ancestry groups had similar LDL-C levels. In all ancestry groups, the proportion of FH-variant carriers treated with lipid-lowering therapy should be improved to reduce future risk of premature coronary heart disease.

Refinement of the diagnostic approach for the identification of children and adolescents affected by familial hypercholesterolemia: Evidence from the LIPIGEN study

Background and aimsWe aimed to describe the limitations of familiar hypercholesterolemia (FH) diagnosis in childhood based on the presence of the typical features of FH, such as physical sings of cholesterol accumulation and personal or family history of premature cardiovascular disease or hypercholesterolemia, comparing their prevalence in the adult and paediatric FH population, and to illustrate how additional information can lead to a more effective diagnosis of FH at a younger age. MethodsFrom the Italian LIPIGEN cohort, we selected 1188 (≥18 years) and 708 (<18 years) genetically-confirmed heterozygous FH, with no missing personal FH features. The prevalence of personal and familial FH features was compared between the two groups. For a sub-group of the paediatric cohort (N = 374), data about premature coronary heart disease (CHD) in second-degree family members were also included in the evaluation. ResultsThe lower prevalence of typical FH features in children/adolescents vs adults was confirmed: the prevalence of tendon xanthoma was 2.1% vs 13.1%, and arcus cornealis was present in 1.6% vs 11.2% of the cohorts, respectively. No children presented clinical history of premature CHD or cerebral/peripheral vascular disease compared to 8.8% and 5.6% of adults, respectively. The prevalence of premature CHD in first-degree relatives was significantly higher in adults compared to children/adolescents (38.9% vs 19.7%). In the sub-cohort analysis, a premature CHD event in parents was reported in 63 out of 374 subjects (16.8%), but the percentage increased to 54.0% extending the evaluation also to second-degree relatives. ConclusionsIn children, the typical FH features are clearly less informative than in adults. A more thorough data collection, adding information about second-degree relatives, could improve the diagnosis of FH at younger age.

Kaedah Diagnostik Semasa dan Penggunaan Ujian Titik Penjagaan Pantas (POC) Bagi Mendiagnos Hiperkolesterolemia Famili (FH)

Familial hypercholesterolemia (FH) is an autosomal dominant inherited genetic disease characterized by increased concentrations of low-density lipoprotein (LDL-C) cholesterol in the blood. The risk of premature coronary heart disease in FH patients may increase without early treatment. Advancement in molecular biology techniques has enable early detection and diagnosis of FH. These techniques are cost-effective and have a shorter turnaround time. The current diagnostic tools available for FH diagnosis involving algorithm-based scoring criteria and various molecular diagnosis methods including next-generation sequencing (NGS), Sanger sequencing, Multiplex ligation-dependent probe amplification (MLPA) and DNA hybridisation assay are discussed in this review. However, molecular genetic testing is not widely available due to time-consuming procedures, high cost and requires trained personnel. Thus, this 36 review highlights the use of point of care (POC) testing as an approach to diagnose FH, particularly in countries lacking infrastructure and expertise in this field. Lateral flow testing (LFA) has gained attention as a POC diagnostic tool due to its simplicity, low cost and involved simple procedure and settings. The advantages of LFA made this technique a potential tool in addressing challenges in diagnosing FH, particularly for early diagnosis of family members.

Prevalence of familial hypercholesterolemia in a country-wide laboratory network in Pakistan: 10-year data from 988, 306 patients

IntroductionFamilial hypercholesterolemia (FH) is a modifiable risk factor for premature coronary heart disease but is poorly diagnosed and treated. We leveraged a large laboratory network in Pakistan to study the prevalence, gender and geographic distribution of FH. MethodologyData were curated from the Aga Khan University Hospital clinical laboratories, which comprises of 289 laboratories and collection points spread over 94 districts. Clinically ordered lipid profiles from 1st January 2009 to 30th June 2018 were included and data on 1,542,281 LDL-C values was extracted. We used the Make Early Diagnosis to Prevent Early Death (MEDPED) criteria to classify patients as FH and reported data on patients with low-density liporotein -cholesterol (LDL-C) ≥ 190 mg/dL. FH cases were also examined by their spatial distribution. ResultsAfter applying exclusions, the final sample included 988,306 unique individuals, of which 24,273 individuals (1:40) had LDL-C values of ≥190 mg/dL. Based on the MEDPED criteria, 2416 individuals (1:409) had FH. FH prevalence was highest in individuals 10–19 years (1:40) and decreased as the patient age increased. Among individuals ≥40 years, the prevalence of FH was higher for females compared with males (1:755 vs 1:1037, p < 0.001). Median LDL-C for the overall population was 112 mg/dL (IQR = 88-136 mg/dL). The highest prevalence after removing outliers was observed in Rajan Pur district (1.23% [0.70–2.10%]) in Punjab province, followed by Mardan (1.18% [0.80–1.70%]) in Khyber Pakhtunkhwa province, and Okara (0.99% [0.50–1.80%]) in Punjab province. ConclusionThere is high prevalence of actionable LDL-C values in lipid samples across a large network of laboratories in Pakistan. Variable FH prevalence across geographic locations in Pakistan may need to be explored at the population level for intervention and management of contributory factors. Efforts at early diagnosis and treatment of FH are urgently needed.

Management of ST Elevation Myocardial Infarction in a 17 years Girl in A Tertiary Care Hospital

Background: Worldwide, myocardial infarction (MI) is an important cause of death. Number of AMI among young adult is increasing day by day in Bangladesh. Acute MI occurs most commonly at an older age. However, the incidence of acute MI in adolescents is increasing. This is partly due to an increase in cardiovascular risk factors (e.g. smoking, unhealthy diet), which might lead to premature atherosclerosis. However, several non-atherosclerotic causes of MI in adolescents are also described in the literature, such as vascular spasm due to the use of cocaine, amphetamine etc. We may assume that acute MI is not considered to be the most likely cause of chest pain in adolescents. Therefore, the risk of a dramatic outcome in this patient category may be significant. Myocardial infarction (MI) in the young (age &lt; 45 years) is a significant problem; however, there is a scarcity of data on premature coronary heart disease and MI in the adolescent patients. MI in adolescents (age between 10–19 years) is extremely rare.Premature AMI, particularly in the setting of obstructive CAD and/or female sex, is an aggressive disease with high rates of recurrence and mortality, attributed largely to suboptimal control of modifiable risk factors.1 Collet et al2 reported that 1 in 3 patients with premature (≤45 years of age) CAD, of whom the majority experienced AMI, had at least 1 recurrent event over a follow-up period of 20 years. Strong independent predictors for recurrent events were persistent smoking, diabetes, hypertension. We present a case of the 17-year-old girl with extensive ST-segment elevated anterior wall myocardial infarction and found to have complete thrombotic occlusion of proximal left anterior descending coronary artery.&#x0D; Central Medical College Journal Vol 6 No 1 January 2022 Page: 49-53

A Machine Learning Model to Aid Detection of Familial Hypercholesterolemia

BackgroundPeople with monogenic familial hypercholesterolemia (FH) are at an increased risk of premature coronary heart disease and death. With a prevalence of 1:250, FH is relatively common; but currently there is no population screening strategy in place and most carriers are identified late in life, delaying timely and cost-effective interventions. ObjectivesThe purpose of this study was to derive an algorithm to identify people with suspected monogenic FH for subsequent confirmatory genomic testing and cascade screening. MethodsA least absolute shrinkage and selection operator logistic regression model was used to identify predictors that accurately identified people with FH in 139,779 unrelated participants of the UK Biobank. Candidate predictors included information on medical and family history, anthropometric measures, blood biomarkers, and a low-density lipoprotein cholesterol (LDL-C) polygenic score (PGS). Model derivation and evaluation were performed in independent training and testing data. ResultsA total of 488 FH variant carriers were identified using whole-exome sequencing of the low-density lipoprotein receptor, apolipoprotein B, apolipoprotein E, proprotein convertase subtilisin/kexin type 9 genes. A 14-variable algorithm for FH was derived, with an area under the curve of 0.77 (95% CI: 0.71-0.83), where the top 5 most important variables included triglyceride, LDL-C, apolipoprotein A1 concentrations, self-reported statin use, and LDL-C PGS. Excluding the PGS as a candidate feature resulted in a 9-variable model with a comparable area under the curve: 0.76 (95% CI: 0.71-0.82). Both multivariable models (w/wo the PGS) outperformed screening-prioritization based on LDL-C adjusted for statin use. ConclusionsDetecting individuals with FH can be improved by considering additional predictors. This would reduce the sequencing burden in a 2-stage population screening strategy for FH.

Estimation of health literacy levels in patients with cardiovascular diseases in a Gulf country

IntroductionCardiovascular diseases (CVDs) are the leading cause of mortality worldwide. In the United Arab Emirates (UAE), the prevalence of deaths associated with CVD is higher than the global average, and the incidence of premature coronary heart disease is 10–15 years earlier than in Western nations. In patients with CVD, inadequate health literacy (HL) is significantly associated with poor health outcomes. The goal of this study is to assess HL levels among patients with CVD in the UAE to develop effective health system strategies for disease prevention and management.MethodsA nationwide cross-sectional survey to assess HL levels in patients with CVD was conducted between January 2019 and May 2020 in the UAE. The association between health literacy level with patient age, gender, nationality, and education was determined using the Chi-Square test. The significant variables were further analyzed by ordinal regression.ResultsOf 336 participants (86.5% response rate), approximately half 51.5% (173/336) of the respondents were women, and 46% (146/336) of them attained high school level of education. More than 75% (268/336) of the participants were above the age of 50 years. Overall, 39.3% (132/336) of respondents possessed inadequate HL, and 46.4% (156/336) and 14.3% (48/336) demonstrated marginal and adequate HL, respectively. Inadequate health literacy was more prevalent among women, as compared to men. Age was significantly associated with HL levels. Participants under age 50 had higher adequate HL levels 45.6% (31/68), (95% CI (3.8–57.4), P < 0.001). There was no correlation between education and health literacy levels.ConclusionThe inadequate HL levels found in outpatients with CVD is a major health concern in the UAE. To improve population health outcomes, health system interventions, including targeted educational and behavioral programs for the older population are necessary.