ORIGINS-RCE is an observational, cross-sectional, two-arm study aimed at determining if an individual's ethnic origin influences the number of blood vessel-forming stem cells in the bloodstream. Circulating progenitor cells will be enumerated and the distribution patterns of these cell types will be assessed to determine if these parameters differ between individuals of South Asian origin and European origin. Specifically, this study will evaluate if differential regenerative cell exhaustion (RCE) may account, at least in part, for the differences in cardiovascular risk reported between individuals of South Asian vs European origin.

Individuals of South Asian origins have been reported to be at higher risk of ischemic heart disease than those of European origins. While differential morphometries and culturally related behavioural habits are believed to account in part for the difference, there is growing evidence that cardiometabolic risk factors can accelerate pro-vascular progenitor cell depletion and dysfunction. The cumulative effects that aberrant regenerative cell exhaustion (RCE) have on vessel repair accordingly increases the risk of atherothrombotic events.

ORIGINS-RCE is an observational, cross-sectional, two-arm study that will evaluate the progenitor cell profiles of peripheral blood samples from 120 individuals (60 of South Asian origins, 60 of European origins). The working hypothesis is that individuals of South Asian and European origins have innately different progenitor profiles that can be further altered by behavioural/cultural habits. The resultant differences in RCE capability will affect the balance between pro-inflammatory and vessel repair functions that in turn contribute to the contrasting cardiometabolic risks exhibited between the two study cohorts.

1. Adults 40 years of age or older of South Asian origin or white European origin as defined by the following:

   1. South Asian defined as any individual who identifies as Anglo-Indian, Bangladeshi, Bengali, Bhutanese, Goan, Gujarati, Indian, Jatt, Kashmiri, Maharashtrian, Malayali, Nepali, Pakistani, Punjabi, Sindhi, Sinhalese, Sri Lankan, Tamil, Telugu, or other South Asian.
   2. White Europeans or European Origin defined as any individual who identifies as from western European, other northern European, southern European, eastern European or other European origins.

2. Willing and able to provide written informed consent and comply with study requirements.

3. Must meet criteria of one of the two following groups:

   1. Established diabetes (HbA1c ≤10.5%) with no CVD but meets 1 or more of the following criteria:

      • On insulin therapy
      • Cigarette smoker or stopped smoking within 3 months
      • Documented hypertension (as defined by a sitting blood pressure at screening of ≥130/80 mmHg) OR currently on antihypertensive therapy
      • History of treated or untreated dyslipidemia
      • High sensitivity C-reactive protein ≥2.0 mg/L
      • eGFR 30 to 60 mL/min/1.73m^2
      • Documented micro- or macro-albuminuria

   2. Established CVD and meets 1 or more of the following criteria within 10 years prior to screening:

      • Documented coronary artery disease (CAD)
      • Documented cerebrovascular or carotid disease
      • Documented peripheral artery disease (PAD)

Exclusion Criteria:

1. Severe congestive heart failure (as defined by New York Heart Association - class IV)
2. Any life-threatening disease expected to result in death within the next 2 years
3. Any malignancy not considered cured (except basal cell carcinoma of the skin). A subject is considered cured if there has been no evidence of cancer recurrence for the 5 years prior to screening.
4. Known severe liver disease
5. White blood cell count ≥15 x 10^9/L
6. Active infectious disease requiring antibiotic or anti-viral agents
7. Known acquired immunodeficiency syndrome such as HIV
8. On oral steroid therapy (e.g. prednisone or other corticosteroids) or other immunosuppressive agents (e.g. methotrexate)
9. Treated autoimmune disorder (excluding type 1 diabetes)

Participants will be identified from primary care and cardiology outpatient clinics in the Greater Toronto Area using paper-based and electronic medical records.