In an apparently healthy multi-ethnic population of Aboriginal, Chinese, European and South Asian men and women, we explored the association between HTGW and indices of subclinical atherosclerosis. The findings of our study indicate that HTGW was significantly and positively associated with IMT and total area in both men and women. The positive association between HTGW and presence of plaques was significant for men; but it did not reach statistical significance for women. Significant associations between HTGW and indices of subclinical atherosclerosis were independent of age, ethnicity, smoking behaviour, and levels of physical activity. However, once analyses were adjusted for all traditionally measured risk factors for atherosclerosis, the associations of HTGW with indices of subclinical atherosclerosis were no longer significant.
Our study is congruent with studies performed in populations with diabetes mellitus[15, 16], chronic kidney disease, and those infected with human immunodeficiency virus that found a positive association between HTGW and subclinical atherosclerosis. In our study, as indicated by total area and presence of plaques, individuals with either Elevated WC or Elevated TG had more carotid atherosclerosis than individuals without HTGW; while greatest carotid atherosclerosis was observed among men and women with HTGW suggesting that the combination of a large WC and elevated TG results in greater CVD risk. Indeed, the phenotype of HTGW has previously been shown to be associated with elevated cardiometabolic risk factors[13, 24–28]. Additionally, multiple prospective studies reported an increase in risk of developing cardiovascular disease[22, 29–31] and diabetes[32, 33] among individuals with HTGW phenotype further highlighting the utility of HTGW as a preventative screening tool.
It has been proposed that elevated fasting TG, in the presence of increased WC, represent a marker of individual’s relative inability to store energy surplus in the subcutaneous adipose tissue (a protective metabolic sink); consequently, HTGW could be a simple marker of visceral adipose tissue (dysfunctional adipose tissue) and its metabolic complications resulting from insulin resistance[14, 34]. Indeed, it has recently been reported that, among subjects with type 2 diabetes, HTGW identifies subset of individuals with greater degree of visceral adiposity and subclinical atherosclerosis (15). Of importance, although there is an established link between insulin resistance and coronary artery disease (CAD), presence of HTGW was found to be associated with increased CAD risk in both normoglycemic and insulin resistant individuals.
The rationale for measuring and interpreting WC along with TG when screening for individuals at increased cardiometabolic risk is due to a fact that not all individuals with increased WC have elevated VAT and are at increased risk for CAD (14). Indeed, it has been shown that isolated increase in WC or isolated hypertriglycerideamia showed no association with increase in CAD risk, while simultaneous presence of elevated WC and fasting TG (HTGW) was associated with a significant increase in CAD disease (13). Additionally, although cardiovascular risk of men was significantly higher than that of women in our study, which is most likely due to differences in body fat accumulation between sexes[37, 38], greatest atherosclerosis was observed in both men and women with HTGW compared to their counterparts with isolated elevated WC or TG. Thus, simultaneous measurement and interpretation of WC and fasting TG can be a powerful tool to identify both men and women characterized by the atherogenic triade (hyperinsulinemia, elevated apolipoprotein B, and small, dense LDL-C) and at high risk for CAD (13, 27).
The strength of our study lies in exploring the association between HTGW and subclinical atherosclerosis in an apparently healthy and a multiethnic population, in using several markers of subclinical atherosclerosis (IMT, total area and presence of carotid plaques), and exploring whether the effect of HTGW on subclinical atherosclerosis persists over and above traditional risk factors for atherosclerosis. Our findings that HTGW phenotype is associated with subclinical atherosclerosis in apparently healthy men and women, irrespective of ethnicity, suggests an important role that HTGW may play in primary care practice in identifying patients at risk for atherosclerosis. The use of HTGW would largely expedite and simplify triaging of patients by identifying those "in need" of aggressive atherosclerosis prevention, thereby decreasing the amount of time and complex testing a primary health care practitioner would spend screening for such patients and potentially translate in lower health care costs. Moreover, this quick assessment would further allow a primary care health practitioner to spend more time in counselling a patient on how to decrease their risk for atherosclerosis.
Patients seen by specialists often already have documentation of traditional risk factors and so further assessment for HTGW may not necessarily add information toward atherosclerosis risk since we observed the effect of HTGW on subclinical atherosclerosis was no longer significant once all traditional atherosclerosis risk factors were added to the model. However, given a strong association of HTGW with cardiometabolic risk factors[12, 13, 24–28] and its ability to predict cardiovascular disease event, HTGW may be used as a simple and inexpensive tool in clinical practice to monitor patients’ changes (improvement/deterioration) in cardiometabolic risk. Additionally, this simple tool could also provide greater incentive to patients for lifestyle change, as they can easily track the effect of lifestyle changes on their cardiometabolic risk.
Despite its potential benefits in identifying individuals at increased risk for atherosclerosis, the widespread use of HTGW as a screening tool may be limited due to the lack of routine measurement of WC in clinical practice. Indeed, in a recently published study, Gupta et al. (2012) surveyed Canadian primary care physicians and found that WC was routinely measured by only 6% of physicians. This finding contrasts with the knowledge that 80% of surveyed physicians considered WC to be a vital sign. This discrepancy may be due to a notion amongst clinicians that WC is a tool for research purposes only; a lack of effort to continuously inform physicians about the clinical usefulness of the routine WC measurements; and a lack of a standardized protocol for WC measurement. There is a concern that a lack of standardized protocol for measurement of WC may influence clinical decision-making[41–43]. However, it has been reported that the reproducibility of WC measurement is high regardless of the measurement site and that the WC measurement protocol has no significant influence on the association of WC with CVD, diabetes, all-cause and CVD mortality. Given the simplicity, high reproducibility of and low costs associated with the WC measurement, it has been argued that WC should be used by the medical community more consistently.
Ethnic-specific WC targets may pose an additional challenge in identifying individuals with HTGW and hence at risk for atherosclerosis. While using current definition for HTGW, we found that ethnicity did not modify the association between HTGW and indices of atherosclerosis; however, our results indicate significant ethnic differences in the distribution of HTGW components which is most likely driven by body fat accumulation shown to be different in distinct ethnic groups[45, 46]. Thus, we believe that further exploration on the role of ethnicity in the association between HTGW and subclinical atherosclerosis is warranted given the already established ethnic differences in CVD risk[47, 48].
There are limitations to the study design as it is cross-sectional rather than prospective. Future research should employ a prospective study design to determine causal relationships. Our study sample may not be representative of a general population given that our participants were between ages of 30 and 65 and purposely recruited across a range of BMI values. However, this approach to recruitment may be advantageous, as it allowed us to explore the association between HTGW and atherosclerosis in a population with diverse body sizes. Furthermore, due to a difficulty in identifying individuals of Chinese origin with BMI of 30 and higher, the target for the upper BMI range of Chinese individuals was changed to a BMI of 28 or higher. However, we believe that this slight modification in the recruitment strategy did not influence our study results where Chinese individuals were shown to have lower prevalence of HTGW and hence lower cardiovascular risk compared to their ethnic counterparts; as already reported in the literature[48, 49].