Background Patients with premature coronary artery disease (CAD) have high rates of recurrent events and death. Information on long‐term adherence to lipid‐lowering therapy (LLT) and trends in medication‐taking behavior in premature CAD is limited. We assessed temporal trends in LLT, factors associated with adherence to LLT, and the consequences of low adherence in a longitudinal cohort of patients with premature CAD. Methods Using a cardiovascular registry and administrative databases, we analyzed temporal changes in rates and predictors of adherence to LLT as well as the association between adherence and cardiovascular outcomes in patients with premature obstructive CAD from 2000 to 2017. Results Among 11 411 patients with premature CAD, 27.6% were women and the mean±SD age was 46.1±5.05 years. The proportion with good first‐year adherence to LLT increased from 54.9% to 71.4% (P<0.001) over the study period; however, changes in third‐year adherence were much smaller (44.4% versus 47.3%; P<0.001). Use of high‐intensity LLT increased over the same time period from 26.7% to 92.0% (P<0.001). More severe presentation, revascularization at presentation, absence of chronic kidney disease, and nonsmoking were consistently associated with better adherence across the study time frame. Rural residence, female sex, and substance use disorder were associated with poor adherence only in later years. Good adherence was associated with a lower risk of cardiovascular outcomes, including death (hazard ratio [HR], 0.45 [95% CI, 0.39–0.55]) and myocardial infarction (HR, 0.53 [95% CI, 0.45–0.63]). Conclusions Use of high‐intensity LLT and short‐term adherence are improving in patients with premature CAD, but different strategies are needed to increase long‐term adherence to prevent recurrent cardiovascular events.

Background Rates of premature coronary artery disease (CAD) are stagnant, and the prevalence of cardiovascular risk factors in young and middle-aged adults is increasing. Lipid-lowering therapy (LLT) is effective in preventing CAD but is underutilized in younger patients. The reasons for and consequences of this underutilization are not fully understood. Objectives The purpose of the study was to assess prepresentation health care encounters, eligibility for, usage patterns, and predictors of initiation of LLT and its relationships with the severity of clinical presentation of CAD. Methods Using administrative databases and a clinical registry, we analyzed health care encounters, cardiovascular risk, and medication dispensations in females <55 and males <50 years old who presented with angiographically confirmed premature CAD. Results Among 11,445 patients (27.6% females, age 46.14 ± 5.05 years) in the administrative database, in the 3 years before presentation, 93.3% were eligible for lipid screening and 92.2% had health care visits, but only 14.8% received LLT dispensations, and 5.9% displayed good adherence. In multivariable analysis, females (OR: 0.75; 95% CI: 0.65-0.86), rural residents (OR: 0.75; 95% CI: 0.62-0.91), and smokers (OR: 0.65; 95% CI: 0.57-0.74) were less likely to receive LLT. High-intensity LLT vs no LLT was associated with lower odds of presenting with acute coronary syndrome (OR: 0.25; 95% CI: 0.19-0.38). Among 470 clinical registry participants (27.4% females, mean age 45.72 ± 5.07 years), 70.2% had lipids assessed, 55.7% were eligible for LLT based on the estimated cardiovascular risk, 18.9% received treatment recommendations, and 12.1% received dispensations of LLT before presentation. Conclusions Prior to presenting with premature CAD, most patients had medical encounters, but few received LLT, demonstrating a substantial gap in prevention.

Background: Screening first-degree relatives (FDRs) of patients with premature coronary artery disease (CAD) is recommended but not routinely performed. Objectives: To assess the diagnostic yield and impact on clinical management of a clinical and imaging-based screening program of FDRs delivered in the setting of routine clinical care. Methods: We recruited FDRs of patients with premature CAD with no personal history of CAD and prospectively assessed for: 1) cardiovascular risk and presence of significant subclinical atherosclerosis (SA) defined as plaque on carotid ultrasound, stenosis >50% or extensive atherosclerosis on coronary computed tomography angiography, or coronary artery calcium scores >100 Agatston units or >75% percentile for age and sex; 2) utilization of preventive medications and lipid levels prior enrolment and after completion of the assessment. Results: We assessed 132 FDRs (60.6% females), mean (SD) age 47(17) years old. Cardiovascular risk was high in 38.2%, moderate in 12.2%, and low in 49.6% of FDRs. SA was present in 34.1% of FDRs, including 12.5% in low, 51.9% in moderate, and 55.0% in high calculated risk groups. After assessment, LLT was initiated in 32.6% of FDRs and intensified in 16.0% leading to mean (SD) LDL-C decrease of 1.07(1.10) mmol/L in patients with high calculated risk or SA. LLT was recommended to all patients with high calculated risk, but those with SA were more likely to receive the medications from pharmacies (93.3% vs 60.0%, p = 0.006). Conclusion: Screening the FDRs of patients with premature CAD is feasible, may have high diagnostic yield and impact risk factor management.

Background: Heart disease is the leading cause of premature death for women in Canada. Ischemic heart disease is categorized as myocardial infarction (MI) with no obstructive coronary artery disease (MINOCA), ischemia with no obstructive coronary arteries (INOCA), and atherosclerotic obstructive coronary artery disease (CAD) with MI (MI-CAD) or without MI (non-MI-CAD). This study aims to study the prevalence of traditional and nontraditional ischemic heart disease risk factors and their relationships with (M)INOCA, compared to MI-CAD and non-MI-CAD in young women. Methods: This study investigated women who presented with premature (at age <= 55 years) vasomotor entities of (M)INOCA or obstructive CAD confirmed by coronary angiography, who are currently enrolled in either the Leslie Diamond Women's Heart Health Clinic Registry (WHC) or the Study to Avoid Cardiovascular Events in British Columbia (SAVEBC). Univariable and multivariable regression models were applied to investigate associations of risk factors with odds of (M) INOCA, MI-CAD, and non-MI-CAD. Results: A total of 254 women enrolled between 2015 and 2022 were analyzed, as follows: 77 with INOCA and 37 with MINOCA from the registry, and 66 with non-MI-CAD and 74 with MI-CAD from the study. Regression analyses demonstrated that migraines and preeclampsia or gestational hypertension were the most significant risk factors, with a higher likelihood of being associated with premature (M)INOCA, relative to obstructive CAD. Conversely, the presence of diabetes and a current or previous smoking history had the highest likelihood of being associated with premature CAD. Conclusions: The risk factor profiles of patients with premature (M) INOCA, compared to obstructive CAD, have significant differences.

BackgroundHeart disease is the leading cause of premature death for women in Canada. Ischemic heart disease (IHD) is categorized as myocardial infarction (MI) with no obstructive coronary artery disease (MINOCA), ischemia with no obstructive coronary arteries (INOCA), and atherosclerotic obstructive coronary artery disease (CAD) with MI (MI-CAD) or without MI (non-MI CAD). This study aims to study the prevalence of traditional and non-traditional IHD risk factors and their relationships with (M)INOCA compared to MI-CAD and non-MI CAD in young women.MethodsThis study investigated women who presented with premature (≤55 years old) vasomotor entities of (M)INOCA or obstructive CAD confirmed by coronary angiography, who are currently enrolled in either the Leslie Diamond Women’s Heart Health Clinic Registry (WHC) or the Study to Avoid cardioVascular Events in BC (SAVEBC). Univariable and multivariable regression models were applied to investigate associations of risk factors with odds of (M)INOCA, MI-CAD or non-MI CAD.ResultsA total of 254 women enrolled between 2015-2022 were analyzed: 77 INOCA and 37 MINOCA from the WHC and 66 with non-MI CAD and 74 MI-CAD from SAVEBC. Regression analyses demonstrated that migraines and preeclampsia/gestational hypertension were the most significant risk factors with higher likelihood to associate with premature (M)INOCA relative to obstructive CAD. Conversely, the presence of diabetes and a current or previous smoking history had the highest likelihood to associate with premature CAD.ConclusionThere are significant differences in the risk factor profiles of patients with premature (M)INOCA compared to obstructive CAD.

Background:Lipid-lowering therapy (LLT) is a central aspect of the treatment of patients with coronary artery disease (CAD), and the benefits of LLT accrue over time. However, there are limited real-world data on longitudinal lipid control in patients with premature CAD. Objectives:The purpose of this study was to assess longitudinal attainment of guideline-recommended lipid goals and outcomes in a contemporary cohort of patients with premature CAD. Methods:We enrolled males younger than 50 years and females younger than 55 years with coronary stenosis of >50% and examined achievement of lipid goals, LLT characteristics, and cardiovascular outcomes (major adverse cardiovascular event [MACE]). Results:Of 476 patients who presented with acute coronary syndrome (ST-elevation myocardial infarction, non-ST-segment elevation myocardial infarction, unstable angina) (68%), stable angina (28%), or other symptoms, 73.2% achieved low-density lipoprotein cholesterol (LDL-C) <1.8 mmol/L on at least 1 occasion, but only 27.3% consistently stayed in the target range for 3 years after diagnosis. Although 73.9% of patients received high-intensity LLT at the time of diagnosis, only 43.5% had good adherence over the following 3 years. In multivariable analysis, 1 mmol/L increase in time-weighted average exposure to LDL-C, but not the lowest achieved LDL-C, was associated with a higher risk of MACE, hazard ratio 2.02 (95% CI: 1.48-2.76), when adjusted for sex, age, hypertension, diabetes, and smoking. Conclusions:We found low rates of longitudinal lipid target achievement in patients with premature CAD. Cumulative LDL-C exposure, but not lowest achieved LDL-C, was associated with risk of MACE. This highlights the critical importance of longitudinal control of lipids levels and identifies opportunities to improve LLT and maximize the time-dependent benefits of lipid-lowering.

Introduction: Premature coronary artery disease (CAD) incidence is increasing globally. South Asians (SA) have a disproportionately high burden of atherosclerotic cardiovascular disease (ASCVD). However, the effect of SA ethnicity on the risk of recurrent events in patients with premature CAD has not been prospectively evaluated. Methods: Patients in the SAVEBC and UK biobank (UKB) registries were enrolled and stratified by ethnicity and presence of premature CAD. The co-primary outcomes were to compare proportion of premature CAD and the incidence of recurrent ASVCD events. Secondary exploratory outcomes included describing demographic, physical, biochemical variables between cohorts. Results: 11,136 patients were included, 1,129 (143 SA; 21%) were from SAVEBC and 10,007 (400 SA; 4.0%) from UKB. There was a higher proportion of premature CAD in SA compared to Caucasians in UKB (5.2% vs. 2.0%, p < 0.001). Similarly, SA were overrepresented in SAVEBC (21% of cohort vs. 7.9% of British Columbia population). SA compared to Caucasians with premature CAD had increased prevalence of diabetes (SAVEBC: 20.1% vs 13.8%, p=0.08; UKB: 37.5% vs 18.0%, p<0.001), and lower mean HDL cholesterol (SAVEBC: 1.4±0.4 vs 1.5±0.4, p=0.21; UKB: 1.1±0.3 vs 1.2±0.3, p<0.001). SA had more diffuse disease reflected by more coronary segments affected (4.9±3.0 vs. 4.1±2.6, p=0.05), and a trend towards more affected coronary vessels compared to Caucasians (1.31±1.4 vs. 0.61±0.91, p=0.14). SA had greater incidence of recurrent ASCVD vs. Caucasians (4.19 vs. 3.08 events per 100 P-Y; incidence rate ratio p-value < 0.001). SA had higher risk of recurrent ASCVD events (HR 1.35, 95% CI 1.13,1.61, p<0.001). SA ethnicity remained a predictor of recurrent events on adjusted COX regression (HR 1.24, 95% CI 1.03,1.48, p=0.02). Conclusion: Using two prospective registries, SA had a higher proportion of premature CAD and recurrent cardiovascular events with shorter time to recurrent events. Some risk may be explained by adverse cardiometabolic profiles, however significant risk mechanisms are yet to be elucidated. Understanding the unique mechanisms of cardiovascular risk in SA is critical to appropriately identify high-risk individuals and initiate contemporary preventative therapies.

Background and aims: Familial combined hyperlipidemia (FCHL) is one of the most common inherited lipid phenotypes, characterized by elevated plasma concentrations of apolipoprotein B-100 and triglycerides. The genetic inheritance of FCHL remains poorly understood. The goals of this study were to investigate the poly genetic architecture and cardiovascular risk associated with FCHL.& nbsp;Methods and results: We identified individuals with an FCHL phenotype among 349,222 unrelated participants of European ancestry in the UK Biobank using modified versions of 5 different diagnostic criteria. The prevalence of the FCHL phenotype was 11.44% (n = 39,961), 5.01% (n =17,485), 1.48% (n = 5,153), 1.10% (n = 3,838), and 0.48% (n = 1,688) according to modified versions of the Consensus Conference, Dutch, Mexico, Brunzell, and Goldstein criteria, respectively. We performed discovery, case-control genome-wide association studies for these different FCHL criteria and identified 175 independent loci associated with FCHL at genome-wide significance. We investigated the association of genetic and clinical risk with FCHL and found that polygenic susceptibility to hypercholesterolemia or hypertriglyceridemia and features of metabolic syndrome were associated with greater prevalence of FCHL. Participants with an FCHL phenotype had a similar risk of incident coronary artery disease compared to participants with monogenic familial hypercholesterolemia (adjusted hazard ratio vs controls [95% confidence interval]: 2.72 [2.31-3.21] and 1.90 [1.30-2.78]).& nbsp;Conclusions: These results suggest that, rather than being a single genetic entity, the FCHL phenotype represents a polygenic susceptibility to dyslipidemia in combination with metabolic abnormalities. The cardiovascular risk associated with an FCHL phenotype is similar to that of monogenic familial hypercholesterolemia, despite being~& nbsp;5x more common.

Background: Familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), and elevated lipoprotein (a) (Lp[a]) increase risk of premature coronary artery disease (CAD). The objective of this study was to assess the prevalence of FH, FCHL, elevated Lp(a) and their impact on management in patients with premature CAD. Methods: We prospectively recruited men <= 50 years and women <= 55 with obstructive CAD. FH was defined as Dutch Lipid Clinic Network scores >= 6. FCHL was defined as apolipoprotein B > 1.2 g/L, triglyceride and total cholesterol > 90th population percentile, and family history of premature cardiovascular disease. Lp(a) >= 50 mg/dL was considered to be elevated. Results: Among 263 participants, 9.1% met criteria for FH, 12.5% for FCHL, and 19.4% had elevated Lp(a). Among patients with FH, 37.5% had FH-causing DNA variants. Patients with FH, but not other dyslipidemias, were more likely than nondyslipidemic patients to have received lipid-lowering therapy before presenting with CAD (33.3% vs 12.3%, P = 0.04) and combined lipid-lowering therapy after the presentation (41.7% vs 7.7%, P < 0.001). One year after presentation, 58.3%, 54.5%, and 58.8% of patients with FH, FCHL, and elevated Lp(a) had low-density lipoprotein cholesterol (LDL-C) < 1.8 mmol/L, respectively, compared with 68.0 % in reference group. Patients with FCHL were more likely to have nonehigh-density lipoprotein (HDL) and apolipoprotein B above recommended lipid goals (70.0% and 87.9%, respectively). Conclusions: FH, FCHL, and elevated Lp(a) are common in patients with premature CAD and have differing impact on treatment and achievement of lipid targets. Assessment for these conditions in patients with premature CAD provides valuable information for individualized management.

OBJECTIVES:Despite advances in screening and prevention, rates of premature coronary artery disease (CAD) have been stagnant. The goals of this study were to investigate the barriers to early risk detection and preventive treatment in patients with premature CAD. In particular, we: 1) assessed the performance of the latest versions of major international guidelines in detection of risk of premature CAD and eligibility for preventive treatment; and, 2) investigated real-life utilization of primary prevention with lipid-lowering therapies in these patients.METHODS:We included patients in the Study to Avoid cardioVascular Events in British Columbia (SAVE BC), an observational study of patients with premature (males ​≤ ​50 years, females ​≤ ​55 years) angiographically confirmed CAD. Eligibility for primary prevention and treatment received were assessed retrospectively based on information recorded prior to or at the index presentation with CAD.RESULTS:Of 417 patients (28.1% females) who met the criteria, 94.3% had at least one major cardiovascular risk factor. In the retrospective risk assessment, 41.7%, 61.4%, and 34.3% (p ​< ​0.001) of patients met criteria for initiation of statin therapy, and an additional 13.9%, 8.4%, and 46.8% may be considered for treatment using the American College of Cardiology/American Heart Association, Canadian Cardiovascular Society, and European Society of Cardiology guidelines, respectively. Only 17.1% of patients received statins and 11.0% achieved guideline-recommended lipid goals before presentation. Diabetes and elevated plasma lipid levels were positively associated with treatment initiation, while smoking was associated with non-treatment.CONCLUSIONS:The current versions of major guidelines fail to recognize many patients who develop premature CAD as being at risk. The vast majority of these patients, including patients who have guideline-directed indications, do not receive lipid-lowering therapy before presenting with CAD. Our findings highlight the need for more effective screening and prevention strategies for premature CAD.

Background The incidence of atherosclerotic cardiovascular disease has declined in the past 2 decades. However, these benefits may not extend to young patients. The objective of this work was to assess temporal trends in the incidence, risk profiles, sex‐related differences, and outcomes in a contemporary population of young patients presenting with coronary artery disease (CAD) in British Columbia, Canada. Methods and Results We used a provincial cardiac registry to identify young patients (men aged <50 years, women aged <55 years), with a first presentation of CAD between 2000 and 2016, who had either ≥50% stenosis of ≥1 coronary arteries on angiography or underwent coronary revascularization. A total of 12 519 patients (30% women) met our inclusion criteria. The incidence of CAD remained stable and was higher for men than women (46–53 versus 18–23 per 100 000). Of patients, 92% had at least one traditional cardiovascular risk factor and 67% had multiple risk factors. The prevalence of diabetes mellitus, obesity, and hypertension increased during the study period and was higher for women. Women had fewer emergent procedures and revascularizations. Mortality rates decreased by 31% between 2000 and 2007, then were stable for the remaining 9 years. Mortality was significantly higher for women aged <45 years compared with men. Conclusions The incidence of premature CAD has not declined, and the prevalence of 3 major cardiovascular risk factors increased between 2000 and 2016. The risk burden and mortality rates were worse for women. These data have important implications for the design of strategies to prevent CAD in young adults.

Vertebral fractures in osteoporosis (OP) patients are accompanied by a decrease in quality of life (QoL) and functional limitations. Physical activity is often recommended for such patients to reduce pain, improve QoL, and functional status.Objective. To assess the impact of exercises on QOL, functional performance, and balance in patients with osteoporotic vertebral fractures.Material and Methods. The study included 78 women with vertebral fractures and chronic back pain (40 patients in the study group and 38 patients in the control group). The average age of patients in the study group was 70.7 ± 8.1 years; in the control – 67.6 ± 7.0 years (p = 0.35). The studied parameters did not significantly differ for two groups at the beginning of the study. In the study group, physical exercises were conducted for 40 minutes twice a week during 12 months. Patients in the control group were recommended to follow the same physical activity as it was prior to the study. Evaluation of the studied parameters at study baseline and 12 months later was carried out using the QUALEFFO-41 questionnaire, a computer system for disequilibrium diagnostics and the «Stand up and walk» test.Results. After 12 months, a statistically significant improvement in QoL was observed among patients of the study group, both in the total score (41.2) compared with the control (57.3, p<0.0001), and in values of all domains, as well as results of the «Rise from a sitting position» and «Chasse step» balance tests. After 12 months, the study group showed a statistically significant reduction of time required to execute the «Stand up and walk» test from 12.1 ± 3.8 to 10.8 ± 2.5 s (p = 0.028), while no changes were observed in the control group (11.1 ± 3.4 and 11.1 ± 2.8 s respectively). Exercises improve QoL, functional activity and balance in patients with osteoporotic vertebral fractures.