SAVE BC: The Study to Avoid cardiovascular Events in British Columbia: A Longitudinal Study of Families with Very Premature Atherosclerotic Cardiovascular Disease in British Columbia

A team from St. Paul’s Hospital (SPH), Vancouver General Hospital (VGH), and the University of British Columbia Hospital (UBCH) has established a study to identify, manage, and research index cases with very premature atherosclerotic cardiovascular disease (AsCVD), as well as their first-degree relatives (FDRs) and spouses, in BC. The Study to Avoid cardioVascular Events in British Columbia (SAVE BC) is currently recruiting patients from SPH and VGH, with a goal to expand the program to include all five cardiac catheterization centres in the province in the next 3 to 5 years. It is expected that 1000 to 2000 individuals (index cases, FDRs, and spouses) will be eligible to participate in this program each year across the province.

The SAVE BC program is aimed at a major public health challenge caused by a high burden of premature AsCVD in BC. At two of the five cardiac catheterization centres in BC (SPH and VGH), an average of approximately 300 men ≤ 50 years of age, and women ≤ 55 years of age (referred to here as “very premature AsCVD”), are identified as having ≥ 50% stenosis of at least one major coronary artery, each year (Dr D. Wood, personal communication, 2015). Based on this and other data sources, the SAVE BC team estimates that each year in BC approximately 500 to 1000 men and women in this very premature age category are diagnosed with AsCVD by angiographic or radiological procedures.

Family history is known to be an important independent risk factor for AsCVD.[1] Risk is further increased by a younger age of onset in these FDRs.[2] Despite strong evidence of AsCVD heritability, multiple screening guidelines from major cardiovascular organizations,[3,4] and availability of proven risk-reducing strategies, few FDRs are screened and even fewer receive appropriate treatment.

To address the need for more-structured provincial screening, the SAVE BC program focuses on identifying and screening families with very premature AsCVD. Individuals in these families are at the greatest risk of future cardiovascular events, as it is more likely that the etiology of AsCVD is due to heritable factors, given the early age of disease onset in the family. SAVE BC will potentially unravel some of the genetic mechanisms in affected families, which could lead to improved predictors of disease and strategies for prevention and treatment.

SAVE BC is using a family-based cascade screening approach. After providing consent, enrolled index cases undergo a baseline visit at a SAVE BC referral centre, currently established at UBCH and SPH in Vancouver, with annual follow-up appointments. SAVE BC genetic counselors work with index cases to identify FDRs and spouses, who are then referred to SAVE BC for a baseline assessment. FDRs and spouses who are considered high risk will be screened annually, and those at low or moderate risk will be screened every 3 years. Blood and saliva samples will be collected from all individuals to determine potential genetic risk factors. In the first 12 months, 157 index cases meeting inclusion criteria have provided either written or verbal consent, as well as 53 FDRs and spouses.

As SAVE BC data are analyzed and new information is generated:
•    Patients will receive pertinent individualized clinical data, reports of aggregate study data, and updates regarding relevant publications and guidelines.
•    Primary care physicians will receive pertinent clinical data on their patients.
•    Findings related to the study will be communicated to the medical community and to agencies and ministries involved in health care within BC.
•    The family-based nature of the SAVE BC program, coupled with the focus on large data capture and biological sample collection, has the potential for discovery of novel diagnostic, prognostic and therapeutic biomarkers, that could enable translation into new prevention or treatment opportunities for AsCVD.

In the short term, the SAVE BC program will ensure that this high-risk cohort is appropriately screened, according to relevant national and provincial guidelines.[3,4] Over the longer term, the program aims to reduce the burden of AsCVD in BC in a cost-effective manner and understand the determinants of very premature AsCVD.

Lessons learned may extend to others in the population with AsCVD and could benefit the management of other chronic diseases with a high familial risk. Visit SAVE BC’s new website for more information (www.savebc.ca).
—Rory Sutherland 
UBC MD Candidate, Class of 2019
—Simon Pimstone, MD, PhD, FRCPC
—Kelsey Lynch, MSc, CGC
—Amy English, MSc
—Liam Brunham, MD, PhD, FRCPC

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This article has been peer reviewed.

References

1.    Lloyd-Jones DM, Nam BH, D’Agostino RB, et al. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: A prospective study of parents and offspring. JAMA 2004;291:2204-2211.
2.    Nora JJ, Lortsher RH, Spangler RD, et al. Genetic-epidemiologic study of early onset ischemic heart disease. Circulation 1980:61:503-508.
3.    Anderson TJ, Grégoire J, Pearson GJ, et al. 2016 Canadian Cardiovascular Society guidelines for the management of dyslipidemia for the prevention of cardiovas-cular disease in the adult. Can J Cardiol 2016;32:1263-1282.
4.    BC Ministry of Health. BC Guidelines: Cardiovascular disease – primary prevention. Revised 15 December 2014. www2.gov.bc.ca/gov/content/health/practitioner-professional-resources/bc-guidelines/cardiovascular-disease.