Prevalence and burden of coronary artery disease on computed tomography coronary angiography and its correlation with high-density lipoprotein in the Northern Territory, Australia
Introduction
Coronary artery disease (CAD) is a significant contributor to the gap in life expectancy between Indigenous and non-Indigenous Australians, with a significantly higher prevalence in Aboriginal and Torres-Strait Islander patients (6.3%) in comparison to non-Aboriginal and Torres-Strait Islander populations (3.2%) (1).
Computed tomography coronary angiography (CTCA) is a safe non-invasive imaging test able to demonstrate coronary atherosclerotic plaque (2,3). Plaque burden on CTCA can be characterised by the ‘Leaman score’ which considers plaque attenuation on CT, the degree of luminal stenosis and location within the coronary tree (4). A recently conducted large randomised-control trial suggested early detection of CAD on CTCA can reduce the rate of non-fatal myocardial infarction in comparison to risk factor scores alone (5). However, to date limited work has been done to elucidate how First Nations Australians may benefit from CTCA from a population health and clinical perspective.
In attempting to address the disproportionate burden of CAD in Indigenous Australians, the level of high-density lipoprotein (HDL) is a potential target. The combination of low serum levels of HDL and elevated triglycerides with small, dense low-density lipoprotein (LDL) particles have been termed an ‘atherogenic’ lipid profile (6) and shown to occur more frequently in Indigenous Australians (7). Unfortunately, the use of HDL as a therapeutic target has had limited success to date (8).
This retrospective observational study conducted in the Northern Territory of Australia aimed to demonstrate the presence and burden of CAD in a cohort of patients referred for CTCA and determine whether there is an association with serum HDL, with a focus upon Indigenous Australians.
Patients without a known history of CAD undergoing CTCA at the Royal Darwin and Alice Springs Hospitals between the 1st of March 2013 and the 1st of September 2018 and a lipid profile available on the electronic medical record were included. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The institutional ethics committee of the Northern Territory, Australia approved this study (HREC ref. 2018-3198) and individual consent for this retrospective analysis was waived. Information was derived from reports generated by experienced cardiologists accredited for reporting by the Australian Conjoint Committee for the Recognition of Training in CTCA. The Leaman score was used to determine the burden of CAD (4). CT was performed using an AquilionOne 320-row multi-detector CT (Toshiba Medical Systems, Otawara City, Japan). Raw data was postprocessed for analysis using recognised software (Canon Medical Systems, Otawar City, Japan).
Information with respect to patient age, gender, Indigenous ethnicity, urban or rural location and cardiovascular risk factors was collected. The value for each component of the lipid profile was collected. Information with respect to each variable was not always available—in these instances, the number of patients for whom information was available is tabulated or mentioned with the reporting of that variable.
All nominal variables are presented as both number and percentage. Normally distributed linear variables are presented as mean ± standard deviation whilst non-normally distributed variables are presented as median [interquartile range (IQR)]. Categorical variables were compared using a Pearson Chi-squared analysis while continuous, normally distributed variables were analysed by Student’s t-test or one-way analysis of variance (ANOVA) analysis. Continuous non-normally distributed variables were analysed by Mann-Whitney or Kruskal Wallis tests. Data were analysed using SPSS v25.
We analysed 213 CTCAs, 123 (57.7%) patients were male. First Nations status was not recorded for 26 patients, but 38/187 (20.3%) patients identified as Indigenous Australians. One hundred and nine patients (51.2%) had CAD on CTCA, with no significant difference in lipid profiles between those with or without CAD, including HDL (1.10±0.36 vs. 1.15±0.32 mmol/L, P=0.34). However, these patients were more likely to be male or have a history of hypertension or smoking (Table 1).
Table 1
| Variables | Total No. | No coronary disease | Coronary disease | P value |
|---|---|---|---|---|
| Age (years) | 212 | 43.6±11.0 | 53.2±10.3 | <0.001 |
| Male | 213 | 54/104 (51.9) | 69/109 (63.3) | 0.09 |
| Indigenous ethnicity | 187 | 18/92 (19.6) | 20/95 (21.1) | 0.80 |
| Urban | 209 | 74/103 (71.8) | 76/106 (71.7) | 0.98 |
| Hypertension | 213 | 19/104 (18.3) | 45/109 (41.3) | <0.001 |
| Hyperlipidaemia | 213 | 37/104 (35.6) | 49/109 (45.0) | 0.16 |
| Diabetes | 213 | 15/104 (14.4) | 24/109 (22.0) | 0.15 |
| Ever smoker | 213 | 46/104 (44.2) | 67/109 (61.5) | 0.01 |
| Family history | 213 | 52/104 (50.0) | 45/109 (41.3) | 0.20 |
| Lipid profile | ||||
| Total (mmol/L) | 213 | 4.95±1.11 | 4.92±1.39 | 0.87 |
| HDL (mmol/L) | 213 | 1.15±0.32 | 1.10±0.36 | 0.34 |
| LDL (mmol/L) | 208 | 3.04±1.00 | 3.01±1.23 | 0.86 |
| Triglycerides (mmol/L) | 210 | 1.69±1.04 | 1.82±1.25 | 0.39 |
| Total:HDL ratio | 213 | 4.55±1.25 | 4.78±1.66 | 0.26 |
| HDL <1.0 mmol/L | 213 | 35/104 (33.7) | 42/109 (38.5) | 0.46 |
Data are presented as mean ± standard deviation, or frequency (number and percentage). Where a variable’s quoted number (n=x) is less than 213, it means not every included patient had information for that variable recorded (i.e., for urban status, n=209 means 4 patients did not have a recorded address). CTCA, computed tomography coronary angiography; HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Indigenous and non-Indigenous patients had a similar prevalence (52.6% vs. 50.3%, P=0.80) and burden as adjudged by a Leaman score (6.03±4.66 vs. 6.96±4.82, P=0.44) of CAD. In those with CAD, Indigenous patients had a lower median calcium score, not reaching statistical significance [9 (IQR, 0–79.5) vs. 43 (IQR, 6–92), P=0.10]. Indigenous patients were significantly younger (41.9±8.9 vs. 50.0±11.9 years, P<0.001), had an atherogenic lipid profile with lower mean HDL (0.91±0.32 vs. 1.18±0.33 mmol/L, P<0.001), higher mean triglycerides (2.35±1.69 vs. 1.64±0.98 mmol/L, P=0.001) and a significantly higher total cholesterol: HDL ratio (5.62±1.69 vs. 4.51±1.36, P<0.001) than non-Indigenous patients (Table 2). There was no significant difference in serum LDL (2.83±0.85 vs. 3.15±1.19 mmol/L, P=0.14).
Table 2
| Variables | Total No. | Indigenous | Non-Indigenous | P value |
|---|---|---|---|---|
| Age (years) | 187 | 41.9±8.9 | 50.0±11.9 | <0.001 |
| Male | 187 | 23/38 (60.5) | 84/149 (56.4) | 0.64 |
| Urban | 186 | 14/37 (37.8) | 124/149 (83.2) | <0.001 |
| Hypertension | 187 | 12/38 (31.6) | 44/149 (29.5) | 0.81 |
| Hyperlipidaemia | 187 | 17/38 (44.7) | 62/149 (41.6) | 0.73 |
| Diabetes | 187 | 7/38 (18.4) | 28/149 (18.8) | 0.96 |
| Ever smoker | 187 | 25/38 (65.8) | 76/149 (51.0) | 0.10 |
| Family history | 187 | 20/38 (52.6) | 69/149 (46.3) | 0.49 |
| Lipid profile | ||||
| Total (mmol/L) | 187 | 4.73±1.02 | 5.07±1.32 | 0.14 |
| HDL (mmol/L) | 187 | 0.91±0.32 | 1.18±0.33 | <0.001 |
| LDL (mmol/L) | 183 | 2.83±0.85 | 3.15±1.19 | 0.14 |
| Triglycerides (mmol/L) | 184 | 2.35±1.69 | 1.64±0.98 | 0.001 |
| Total:HDL ratio | 187 | 5.62±1.69 | 4.51±1.36 | <0.001 |
| HDL <1.0 mmol/L | 187 | 25/38 (65.8) | 44/149 (29.5) | <0.001 |
| Coronary disease | ||||
| Prevalence of CAD | 187 | 20/38 (52.6) | 75/149 (50.3) | 0.80 |
| Leaman score | 95 | 6.03±4.66 | 6.96±4.82 | 0.44 |
Data are presented as mean ± standard deviation, or frequency (number and percentage). Where a variable’s quoted number (n=x) is less than 187, it means not every included patient had information for that variable recorded (i.e., for urban status, n=186 means 1 patient did not have a recorded address). Leaman score was only calculated for patients with CAD. HDL, high-density lipoprotein; LDL, low-density lipoprotein; CAD, coronary artery disease.
There were 108 patients with documented CAD and a recorded age. These patients were stratified by the presence of very premature (age 18–35 years), premature (age 35–55 years) or mature-onset (age 56 years and older) CAD (Table 3). There was a disproportionate number of Indigenous patients with very premature CAD (66.6% vs. 27.5% vs. 5.4%, P<0.001). A history of previous or active smoking was also significantly associated with very premature and premature CAD (66.7% vs. 72.1% vs. 43.9%, P=0.02). Elements of an atherogenic lipid profile were all significantly associated with very premature or premature CAD in the total cohort: low HDL, 0.71±0.25 vs. 1.09±0.35 vs. 1.18±0.36 mmol/L, P=0.009; high triglycerides, 1.97±1.03 vs. 2.11±1.50 vs. 1.40±0.58 mmol/L, P=0.02; and a high total cholesterol:HDL ratio, 6.77±1.51 vs. 4.88±1.71 vs. 4.42±1.37, P=0.004.
Table 3
| Variables | Total No. | Patients aged 18–35 years | Patients aged 36–55 years | Patients aged 56 years and older | P value |
|---|---|---|---|---|---|
| Age (years) | 108 | 31.50±3.94 | 48.20±4.20 | 63.73±5.71 | <0.001 |
| Male | 108 | 4/6 (66.7) | 41/61 (67.2) | 24/41 (58.5) | 0.66 |
| Indigenous | 94 | 4/6 (66.7) | 14/51 (27.5) | 2/37 (5.4) | <0.001 |
| Urban | 105 | 3/6 (50.0) | 41/58 (70.7) | 31/41 (75.6) | 0.42 |
| Hypertension | 108 | 1/6 (16.7) | 24/61 (39.3) | 19/41 (46.3) | 0.36 |
| Hyperlipidaemia | 108 | 2/6 (33.3) | 25/61 (41.0) | 22/41 (53.7) | 0.38 |
| Diabetes | 108 | 1/6 (16.7) | 14/61 (23.0) | 9/41 (22.0) | 0.94 |
| Ever smoker | 108 | 4/6 (66.7) | 44/61 (72.1) | 18/41 (43.9) | 0.02 |
| Family history | 108 | 4/6 (66.7) | 25/61 (41.0) | 16/41 (39.0) | 0.43 |
| Statin | 108 | 2/6 (33.3) | 29/61 (47.5) | 21/41 (51.2) | 0.71 |
| Lipid profile | |||||
| Total (mmol/L) | 108 | 4.68±1.78 | 4.95±1.32 | 4.95±1.46 | 0.90 |
| HDL (mmol/L) | 108 | 0.71±0.25 | 1.09±0.35 | 1.18±0.36 | 0.009 |
| LDL (mmol/L) | 104 | 3.08±1.70 | 2.94±1.12 | 3.14±1.31 | 0.72 |
| Triglycerides (mmol/L) | 108 | 1.97±1.03 | 2.11±1.50 | 1.40±0.58 | 0.02 |
| Total:HDL ratio | 108 | 6.77±1.51 | 4.88±1.71 | 4.42±1.37 | 0.004 |
| HDL <1.0 mmol/L | 108 | 5/6 (83.3) | 23/61 (37.7) | 14/41 (34.1) | 0.07 |
Data are presented as mean ± standard deviation, or frequency (number and percentage). Where a variable’s quoted number (n=x) is less than 108, it means not every included patient had information for that variable recorded (i.e., for urban status, n=105 means 3 patients did not have a recorded address). HDL, high-density lipoprotein; LDL, low-density lipoprotein.
Discussion
Though we showed no relationship between HDL and the prevalence of CAD on CTCA in our general cohort, we have shown low HDL is associated with premature CAD in those referred for CTCA and both premature CAD on CTCA and an atherogenic lipid profile are more common in Indigenous Australian patients. We have shown that hypertension, smoking and male gender were associated with the presence of CAD on CTCA, emphasising the ongoing importance of all traditional cardiovascular risk factors. However, whether improving elements of the lipid profile, in particular HDL, will contribute to fewer cardiovascular events in this cohort deserves attention.
The causes of low HDL in our cohort remain uncertain. Low HDL is associated with poor cardiovascular outcomes (8) and understanding the causes of it are vital. In Indigenous Australians strong correlative factors have been shown to include type 2 diabetes mellitus, central obesity and chronic inflammation (9). In a remote Northern Territory context, these factors are in turn likely driven by a combination of lower education, poor access to fresh fruits and vegetables, energy insecurity, overcrowded housing and poverty. As such atherogenic lipid profiles, amongst multiple other risk factors and health conditions, are unlikely to improve until the social determinants of health are adequately addressed.
In our cohort Indigenous patients were younger than non-Indigenous patients with the same prevalence and burden of CAD. As the ability to demonstrate CAD on CTCA has been associated with fewer non-fatal myocardial infarctions at follow-up (5), detecting CAD early in Indigenous patients may help prevent ACS. However, only a few studies have looked at the prevalence and predictors of CAD on CTCA in the Northern Territory. A recent study looking at the prognostic value of CTCA in Indigenous patients in Central Australia showed a greater burden of CAD in Indigenous patients when adjusted for age and gender (10). A small study utilising coronary calcium scoring in rural areas has demonstrated a higher burden of coronary calcium in Indigenous Australians in comparison with non-Indigenous Australians (11). Though we demonstrated a signal toward lower calcium scores in Indigenous patients with CAD in our study, these patients were younger than non-Indigenous counterparts and the applicability of calcium scoring in such a relatively young cohort is unclear.
This information should help guide patient selection for CTCA to improve capture of those most likely to benefit: the population of Indigenous patients most likely to benefit from CTCA cannot be simply extrapolated from non-Indigenous cohorts. High-risk populations need individualised risk assessments and targeted prevention and treatment strategies (12). We propose that Indigenous Australians living in rural or remote locations may benefit from CTCA up to 10 years earlier than non-Indigenous counterparts. Further investigation is required to confirm our findings and whether earlier detection leads to improved outcomes in this group.
This study has a number of important limitations including a retrospective design pre-disposing to potential selection and misclassification biases and the absence of test indication or prescribed medical therapies. Data from the entire cohort was not available for every studied variable. Additionally, the sample size is limited and based on random selection, further pre-disposing to possible selection bias.
Our study shows that atherogenic lipid profiles are associated with premature CAD, that Indigenous Australian patients are more likely to have this pattern and that they have the same prevalence and burden of CAD on CTCA as non-Indigenous counterparts despite being significantly younger. Guidelines for the use of CTCA must consider the younger age of atherogenesis in Indigenous patients and more research is needed focussing upon HDL as a potential therapeutic target in CAD in this cohort.
Acknowledgments
Funding: None.
Footnote
Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-23-458/prf
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-23-458/coif). P.J.P. serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from July 2022 to June 2024. D.W. serves as an unpaid editorial board member of Cardiovascular Diagnosis and Therapy from February 2023 to January 2025. P.J.P. reports that he received speaker honoraria ad hoc from AstraZeneca and Boehringer Ingelheim related to antiplatelet/anticoagulant management of coronary syndromes; received support from Eli Lilly and NovoNordisk; and served as unpaid president of Australian Atherosclerosis Society. The other authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the institutional ethics committee of the Northern Territory, Australia (No. 2018-3198). Individual consent for this retrospective analysis was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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