Comparison of cardiac CT angiography coronary artery dimensions and ethnicity in Trinidad: the CADET pilot study

Introduction

Cardiovascular disease (CVD) is the leading cause of mortality in Trinidad and Tobago, accounting for approximately one-quarter of deaths annually.1 Within the last decade, more than half of adult mortality was attributed to the vascular disease spectrum in Trinidad and Tobago.1 CVD is also the principal cause of death among high-income countries and is projected to be the leading cause of death globally by 2030 with an anticipated colossal socioeconomic impact.2

Atherosclerosis is a time-dependent process affecting vascular walls, driven by a complex interplay of environmental and genetic risk factors that gradually progresses to CVD.3 Coronary CT angiography (CCTA) has been progressively used as an imaging modality to diagnose CVD due to cutting-edge technological advancements in spatial and temporal resolution. With the advent of high-slice (64-slice and higher) CT scanners, it is regarded as an accurate and reliable alternative to conventional invasive coronary angiography (ICA).4

Several studies have demonstrated a varying prevalence of coronary artery disease (CAD) among diverse ethnic groups. South Asians demonstrated a comparatively higher incidence of CAD when compared with Caucasian populations.5,6,7,8 Trinidad and Tobago is an ethnically diverse Caribbean island, comprising approximately one-third of Caribbean black, one-third of South Asian and the remainder of mixed ethnicity by the 2011 national census.9,10 A major implicated theory for the increased prevalence of CAD in South Asians has been the relatively innate smaller diameter of CAs compared with other ethnicities.11,12,13 Currently, there is no published data to our knowledge that assesses differences in CA dimensions, an independent risk factor for CAD among the various ethnicities in multiethnic Trinidad and Tobago. This study aimed to determine any significant differences in coronary artery (CA) dimensions at prespecified segments during CCTA compared with ethnicity at an academic tertiary medical centre in Trinidad and Tobago.

Methods and materials

Results

A total of 170 patients who underwent CCTA were enrolled in the study (figure 1). Online supplemental table 1) shows the demographics of the study participants. The mean age was 50.7 years. Almost two-thirds of the patients were female, and half were South Asian in ethnicity, with Caribbean black more than one-third represented. The prevalence of type 2 diabetes mellitus (T2DM) was 15%, hypertension was more than two-fifths, and dyslipidaemia was one-third. The mean body mass index (BMI) was 26.5 kg/m², and the body surface area (BSA) was 1.81/m². There was also a prevalence of almost one-fifth of the use of ACE inhibitors, angiotensin receptor blockers and neprilysin inhibitors, and one-quarter of patients were using aspirin and moderate to high-intensity statins. One-sixth of patients were on calcium-channel blockers, with 4% and 6% on nitrates and clopidogrel, respectively. Two per cent of patients were on insulin and sulfonylurea therapies, while almost one-eight was on metformin. The mean average CAC score was 9.2. No patients experienced SAEs, such as moderate or severe contrast media reactions.

The mean dimensions for the left main and proximal, mid and distal segments of each CA are outlined in table 1. There was no statistically significant disparity of any CA segment dimension for male versus female gender (table 2). All segments displayed a statistically significant difference in CA dimension between South Asian and Caribbean black ethnicity, with the exception of the proximal RCA) (table 3). These findings were replicated when the analysis was adjusted for BSA with the addition of the mid-RCA segment, which was borderline near-significant (p value 0.051) (table 4).

Discussion

The advent of modern-day CCTA has heralded a paradigm shift in evaluating chest pain, especially with cutting-edge technology with respect to spatial and temporal resolution.20 Currently, there is mounting evidence for the clinical utility of CCTA within the CVD spectrum, ranging from subclinical detection of CAD to ACS. It is also a versatile technique in that it can non-invasively quantify plaque burden, including those with high-risk features such as thin-capped fibroatheroma, with high accuracy. Additionally, accrued information on haemodynamic indices and further plaque characterisation may contribute to individualised risk assessment and influence management and treatment options.21 In low-resource settings without the widespread accessibility of advanced intravascular imaging such as intravascular ultrasound (IVUS), optical coherence tomography or coregistration, baseline anatomical CA dimensions in these ethnic subgroups may prove highly informative for PCI.

Several intrinsic and extrinsic factors impact vessel dimensions in patients, including gender, heart size, muscle tone, growth factor hormone, BSA and ethnicity.19,22,23 24 This study uses CCTA to measure CA vessel diameter, often considered a superior assessment technique to ICA. Initially, autopsy studies were considered the gold standard of assessment; however, it was discovered that these measurements were affected by fixation and preservation techniques, thus drawing their validity into question.22 ,25 ,26 CAD occurs within the intima with initially endothelial dysfunction and subsequent injury involving a complex milieu of leucocyte and macrophage proliferation and vascular smooth muscle thickening.27 As a result, the early phase of the inflammatory, immunological process of atherosclerosis can be easily missed with conventional ICA.26 CCTA incorporates the entire vessel diameter inclusive of the vessel lumen and wall thickness, which reflects a more accurate measurement.28 ,29 The results of this study indicate that almost all segments of the coronary vasculature are significantly smaller in South Asians compared with the Caribbean black populations. The findings are concordant with previous studies, which allude to the smaller CAs in South Asians, although the vessel dimensions were overall of a larger calibre, with the caveat that these studies used conventional ICA.19 ,30 Compared with a similar study with CCTA, the respective mean vessel diameters are greater.11,28 30 To the authors’ knowledge, there is no published data comparing CA dimensions between these two ethnicities in the English-speaking Caribbean. However, in studies evaluating other vascular beds such as the carotid arteries, evidence suggests black populations’ vascular dimensions may be larger.31 Several factors may play a contributory role in these observations. The analyses were adjusted based on BSA. Although BMI may be a predictor for CAD, as Kim et al demonstrated, several other studies refute this relationship with conflicting results.32 3334 35 Obesity can be overestimated when BMI is used for adjusted analysis as it does not account for the mass and surface area and different tissue characteristics of adipose and muscle.36 ,37 There is also mounting evidence that BSA may be a more accurate predictor of CAD, as reported by Sion et al.38 This study used this rationale for BSA to mitigate any confounding effects. BSA independently predicts the lumen size of the LAD and left circumflex arteries.39 Previous studies demonstrated that BSA was largely responsible for this ethnic size difference of coronary vessels.19 28

In this study, there were no significant differences in gender (male and female) for any CA dimensions for all segments. Yang et al40 reported that females have generally smaller CAs, approximately 0.3 mm less than men. In that study, other potential confounders such as BSA, T2DM and left ventricular hypertrophy were adjusted, and the statistically significant gender association remained. Other studies, while displaying a similar signal, were limited by relatively small sample sizes and suggested that these observations may be attributed to BSA.23 ,41 ,42 ,43 Hormonal differences are postulated to affect vessel size. Estradiol promotes remodelling and growth both in physiological and pathological processes.44 45 Furthermore, estradiol accentuates endogenous vascular endothelial growth factor (VEGF).44 45 VEGF and basic fibroblast growth factor are pivotal in the migration and proliferation of endothelial cells and play an integral role in angiogenesis and vessel size.44 45 ,46 Oestrogen and its receptors can also initiate repair to endothelial dysfunction and injury areas.

T2DM is more prevalent in developing countries, with a reported prevalence of 50% compared with 20% in developed countries.47 48 In a patient with diabetes, there is a complex milieu of proinflammatory cytokines, VEGF, activated protein C, platelet-derived growth factor and advanced glycation end-products, resulting in endothelial dysfunction. Subsequently, there is macrophage and vascular smooth muscle cell proliferation leading to atheroma formation.27 49 As this process becomes more advanced, the lumen becomes compromised, detected on CCTA.27 Coronary artery remodelling is a phenomenon by which vessel dimension changes in response to atherosclerotic plaque accumulation. This pioneering concept was initially described by Glagov et al in a postmortem histopathological study and confirmed by in vivo IVUS analysis.50 ,51 Two different patterns of coronary remodelling have been described: a compensatory enlargement of the vessel in response to an increased burden of atherosclerotic plaque (positive remodelling) and a failure to enlarge or even vessel attenuation (negative remodelling).52 The latter is a common finding in coronary stenosis of diabetic patients. In cross-sectional studies, negative remodelling has been associated with coronary risk factors, such as hypertension, tobacco use, the type of plaque (calcified, hard plaques) and metabolic control in diabetic patients.51 ,53 ,54 ,55 Initially developed in the early 1990s, the Agatston CAC score is a powerful radiographic marker instrumental in CAD stratification and prognostication. The presence of any degree of CAC in patients with diabetes mellitus translates to a higher risk of all-cause mortality than in patients without diabetes.56 The absence of CAC indicates a low risk of death in the short term, and the annual mortality rate is similar to that of individuals without diabetes.56 Central to the “power of zero” philosophy (CAC score of 0) is whether it reliably excludes CAD and would lead to restratification of low-risk patients with clinical sequelae of less cardiovascular diagnostic testing.57 Current cardiovascular risk stratification using clinical risk score systems and biomarkers is less than ideal in identifying patients at risk for major adverse cardiovascular events (MACE). Machine learning algorithms are also expected to enhance the capabilities of CCTA further. The amalgam of anatomical, functional and biological information accrued by CCTA offers a multifaceted risk stratification of patients for targeted prevention strategies.58

Conclusion

Significantly smaller CA dimensions were observed in South Asian patients compared with Caribbean black patients undergoing CCTA. This study could be clinically significant for Trinidadian patients at risk of developing CAD. Further studies are required to confirm these exploratory findings.