Usefulness of Hypertriglyceridemic Waist

• Hypertriglyceridemic waist (elevated waist girth and triglyceride concentrations) could be a simple and inexpensive way to identify individuals with high levels of visceral fat and the features of the metabolic syndrome.
• The simultaneous presence of an elevated waist circumference and high triglyceride levels increases relative risk of CHD.
• Hypertriglyceridemic waist increases the risk of type 2 diabetes.
• A diagnosis of hypertriglyceridemic waist is not sufficient, however, to assess global CHD risk.

Prevalence data from a representative sample of adults of the province of Québec aged 18 to 74 (Québec Health Survey) has enabled the number of men with hypertriglyceridemic waist in Québec to be quantified [10]. Study results indicated that 19% of adult men in the Québec Health Survey had an elevated waist circumference (≥90 cm) and hypertriglyceridemia (≥2.0 mmol/l) [11]. This percentage increased to 29.2% in the subgroup of men aged 40 to 65. Though different cutoffs were used, the prevalence of this phenotype was similar (19%) in the Tehran Lipid and Glucose Study, which involved more than 4,000 men [14]. The prevalence of hypertriglyceridemic waist was also quantified in a sample of 4,448 men and 4,735 women from the third National Health and Nutrition Examination Survey (NHANES III) [19]. In this study, Kahn and Valdez [19] found that, irrespective of sex, the estimated prevalence of the simultaneous presence of an elevated waist circumference and increased triglyceride levels was about 25%. They also found that the estimated prevalence of this phenotype increased with age and was higher (>40%) in men and women aged 55 to 74. A publication from the “SUpplémentation en VItamines et Minéraux Anti-oXydants” (SU.VI.MAX) study also revealed that 12.1% of their sample of middle-aged men had hypertriglyceridemic waist [17]. Finally, the prevalence of hypertriglyceridemic waist has been quantified in a meta-analysis involving more than 90,000 individuals [28]. The prevalence reached 18% in men and 19% in women [28]. Since obesity, especially abdominal obesity, is fast increasing [29], the prevalence of hypertriglyceridemic waist is expected to follow suit. With overweight/obesity in countries such as Canada, Australia, and the United States already afflicting 50% of the population, hypertriglyceridemic waist would allow physicians to focus on the subgroup of overweight/obese patients (with hypertriglyceridemic waist) at greatest risk of type 2 diabetes and CHD, rather than treating half their patients as a blanket measure.

Additional findings from the first publication on hypertriglyceridemic waist revealed that only the simultaneous presence of elevated waist girth and triglyceride concentrations was associated with coronary artery disease (CAD) assessed by angiography [3]. In a sample of 287 men who underwent an angiographic procedure for symptoms of CAD, men whose waist circumference and triglyceride levels were elevated had higher odds of being diagnosed with significant CAD than men with a waist circumference <90 cm and triglyceride concentrations <2.0 mmol/l (odds ratio: 3.6, 95% CI: 1.17-10.93, p<0.03). In isolation, an elevated waist circumference or hypertriglyceridemia did not significantly increase CAD. Furthermore, in a small study of heart transplant patients, the odds of CAD increased fourfold, though this finding was not statistically significant because of the small sample size (n=83) [13]. The usefulness of hypertriglyceridemic waist and the NCEP-ATP III clinical criteria in establishing risk of all-cause and cardiovascular mortality as well as predicting the annual progression rate of aortic calcification was examined in a sample of more than 550 women followed for 8.5 years [18]. Survival curves analysis for all-cause or cardiovascular mortality indicated that survival rates dropped significantly in women with an elevated waist girth and high triglyceride concentrations compared to women without these conditions. Moreover, relative risk for all-cause mortality (hazard ratio: 2.2, 95% CI: 1.3-3.6, p<0.01) and cardiovascular death (hazard ratio: 4.7, 95% CI: 2.2-9.8, p<0.001) associated with hypertriglyceridemic waist was significant even after adjusting for age, smoking, and LDL cholesterol. These findings were repeated in a sub-analysis that excluded women with diabetes. The annual progression rate of aortic calcification was significantly greater in women meeting the NCEP-ATP III criteria or with hypertriglyceridemic waist. However, the highest rates were observed in subgroups with both high waist girth and triglyceride levels, regardless of the presence/absence of NCEP-ATP III criteria. These criteria alone were not as effective as hypertriglyceridemic waist in predicting the annual progression rate of aortic calcification.

In a 7.5-year prospective study (the SU.VI.MAX study) of 3,430 middle-aged men, using subjects with low waist girth and low triglyceride concentrations as the reference group, investigators reported that the risk of developing CVD over the follow-up only increased significantly among men with hypertriglyceridemic waist after adjusting for age, active smoking, physical activity, systolic blood pressure, diastolic blood pressure, and fasting blood glucose (relative risk: 2.13, 95% CI: 1.21-3.76) [17]. These results were confirmed in the large EPIC-Norfolk prospective study where men and women who had both an increased waist circumference and hypertriglyceridemia had the lowest probability of remaining CAD-free (p<0.001 for both sexes) [30].

Although it has been reported that hyperglycemia (even in the nondiabetic range) increases CAD [31,32], it is not clear whether it is dysglycemia that has a direct impact on CAD risk or the metabolic syndrome frequently observed among dysglycemic patients. This question has been examined, and the results showed that the presence/absence of hypertriglyceridemic waist modulated hyperglycemia-related CAD risk in men [15]. For instance, in the absence of hypertriglyceridemic waist, men with fasting hyperglycemia (in isolation) were not at increased risk of CAD. However, the CAD risk associated with hypertriglyceridemic waist significantly increased in both men with normal glucose levels (<6.1 mmol/l) or with an impaired fasting glucose concentration (6.1-6.9 mmol/l). An investigation of a large sample of men and women from the Hoorn study confirmed these results [26].

The combination of a large waist circumference with elevated triglyceride concentrations increased CVD risk among individuals with either normal or abnormal glucose levels (hazard ratio: 1.82; 95% CI: 1.27-2.62 and 2.68; 95% CI: 1.89-3.81, respectively). Another prospective study tested the hypothesis that hypertriglyceridemic waist, as a covariate of metabolic syndrome features, predicted premature CAD among patients with glucose intolerance or type 2 diabetes [33]. The sample included 1,990 men and women, including 592 patients with impaired glucose tolerance or type 2 diabetes. Survival models revealed that among patients with impaired glucose tolerance or type 2 diabetes, those with hypertriglyceridemic waist experienced their first CAD symptoms 5 years earlier than those without this phenotype. This elevated and earlier risk of CAD was statistically significant (hazard ratio: 2.0; 95% CI: 1.2-3.7, p=0.02). Thus, although the relationship between glucose levels and CVD risk is well established, these findings suggest that the presence/absence of hypertriglyceridemic waist could be useful to clinicians in refining assessment of CVD risk due to a dysglycemic or prediabetic state. The presence of abdominal obesity and hypertriglyceridemia should therefore be a warning sign for physicians.

Hypertriglyceridemic waist has also been shown to be associated with increased type 2 diabetes rates in adult men and women [11,19]. Using data from NHANES III, both men and women aged 40 to 74 with hypertriglyceridemic waist were found to have an estimated diabetes prevalence of 25.4%, with this prevalence being only 8.0% in subjects without this phenotype (relative risk: 3.2: 95% CI: 2.4-4.0) [19]. The odds of developing diabetes was also markedly higher in men of the Québec Health Survey with an elevated waist circumference and high triglyceride concentration [11]. A twelvefold increase in the prevalent odds ratio of diabetes (95% CI: 5.1-27.9, p<0.0001) was observed in men with hypertriglyceridemic waist compared to the reference group of men with both low waist girth and triglyceride levels. The prevalent odds ratio was not as high among obese (body mass index (BMI) ≥30 kg/m²) versus normal weight men (odds ratio: 7; 95% CI: 3.4-13.9, p<0.0001). Furthermore, the metabolic profile of men with hypertriglyceridemic waist was as worse as, if not worse than, that of men with diabetes [11]. The usefulness of hypertriglyceridemic waist to identify individuals with type 2 diabetes has been documented in two meta-analyses [27-28]. The odds ratio for diabetes was 2.69 (95% CI: 2.40-3.01) in a meta-analysis involving more than 190,000 individuals [27] and 4.18 (95% CI: 3.55-4.92) in another meta-analysis involving more than 34,000 individuals [28].

Hypertriglyceridemic waist can also be useful in clinical practice to detect individuals likely to have features of the metabolic syndrome, such as an elevated cholesterol/HDL cholesterol ratio, postprandial hyperlipidemia, hyperinsulinemia, and a dyslipidemic profile typically found in subjects with abdominal obesity. In this regard, Solati et al. [14] reported that 75% of men of the Tehran Lipid and Glucose Study with hypertriglyceridemic waist had four to six risk factors (cholesterol, LDL cholesterol, HDL cholesterol, systolic blood pressure, diastolic blood pressure, and BMI). Other studies have also validated the ability of hypertriglyceridemic waist to identify individuals at high risk of CVD [12,16,19-22]. LaMonte et al. [12] have published evidence that more than two-thirds of women with elevated waist girth and triglyceride concentrations also had hyperinsulinemia as well as increased apolipoprotein B and LDL cholesterol levels. Furthermore, a clear relationship between hypertriglyceridemic waist and the cholesterol/HDL cholesterol ratio, a well-known strong predictor of CHD [34,35], has been reported in several study populations [11,15,19,22]. The prevalence of subjects with a cholesterol/HDL cholesterol ratio ≥6 was almost 50%, whereas it was only 3% among men with both low waist girth and normal triglyceride concentrations (10). Carriers of the hypertriglyceridemic waist phenotype also have deteriorated plasma glucose-insulin homeostasis compared to individuals without this phenotype [11,12,19,21,22]. In addition, a postprandial study revealed that men with hypertriglyceridemic waist had the greatest increase in triglyceride concentrations during the postprandial state compared to control subjects [16]. The latter study also indicated that this phenotype was better at identifying a hyperlipidemic state during the postprandial phase than elevated waist circumference or hypertriglyceridemia measured in isolation.

Although hypertriglyceridemic waist is very helpful in clinical practice as a screening tool for identifying patients with the metabolic syndrome, the presence of hypertriglyceridemic waist does not necessarily mean that the patient is at high absolute risk of CHD. The diagnosis of hypertriglyceridemic waist should therefore not be considered in isolation to quantify global CHD risk. Rather, improved global risk assessment algorithms are needed to quantify diabetes and CVD risk resulting from the presence of classical risk factors as well as capture the additional risk caused by abdominal obesity/insulin resistance-related metabolic markers (metabolic syndrome). This overall risk is referred to as global “cardiometabolic risk” [4]. Cardiometabolic risk encompasses the global risk of CVD and type 2 diabetes associated with classical risk factors, while also taking into account the additional contribution of abdominal obesity/insulin resistance and related metabolic markers (to be identified) to global CVD risk. Whether the clinical criteria of the metabolic syndrome add to global CVD risk remains uncertain and is a matter of debate. Only additional prospective studies to directly measure sophisticated metabolic markers and visceral and subcutaneous adiposity can answer this important question. Once these findings are released, we should be better able to define what constitutes a high-risk abdominal obesity phenotype in various regions of the world and elucidate key determinants of risk in different populations.

In summary, because the metabolic syndrome increases the risk of type 2 diabetes and CVD, a number of organizations have proposed screening approaches to identify patients with features of the metabolic syndrome. However, the range of variables and cutoffs proposed has sometimes left clinicians feeling confused and perplexed. Based on evidence that waist circumference and triglycerides may be as good as other, more demanding approaches such as the NCEP-ATP III criteria, hypertriglyceridemic waist may be the simplest tool available for quick initial screening of the metabolic syndrome in clinical practice. However, additional prospective studies are necessary to validate fasting triglyceride concentrations and waist circumference cutoff values in various ethnic populations, in both sexes, and across different age groups.