Body fat and blood rheology: Evaluation of the association between different adiposity indices and blood viscosity

Abstract

BACKGROUND: In recent years, new measures of body adiposity have been introduced: lipid accumulation product (LAP), body adiposity index (BAI) and body shape index (ABSI). These indices have been demonstrated to better associate with cardiovascular disease than other measures of adiposity.

OBJECTIVES: The aim of the present study was to evaluate if LAP or BAI better associate with blood viscosity than other measures of adiposity (body mass index, BMI; waist circumference, WC; waist-to-hip ratio, W/HR; waist-to-height ratio, W/HtR).

METHODS: 344 subjects were recruited for the present investigation. Exclusion criteria were: diabetes, elevated triglycerides, smoking and drug use. Blood lipids and glucose were measured by routine methods. Blood and plasma viscosity were measured by a cone-plate viscometer. Adiposity measures were computed as previously described.

RESULTS: In simple correlation analyses, blood viscosity (BV) correlated with BMI, BAI, and LAP in males and with LAP in females. Correlations between plasma viscosity and adiposity indices were weak and not statistically significant. Other variables significantly related with BV were: gender, HDL- and LDL-Cholesterol, and triglycerides (p < 0.05). In multiple regression analysis only LAP was associated with BV.

CONCLUSIONS: Our data suggest that LAP index is strongly associated to blood viscosity. This result, along with previous evidence, identifies LAP index as a potential cardiovascular risk marker.

Keywords

Blood rheology adiposity indices cardiovascular risk

1 Introduction

Alterations in hemorheological parameters (i.e. reduced erythrocyte deformability, increased erythrocyte aggregation, increased blood and plasma viscosity) may promote micro and macrovascular damage and as consequence major cardiovascular events [12]. It has been reported that blood viscosity is altered in many physiopathological processes such as diabetes, smoking, aging and obesity [18 , 28].

Obesity is a well-recognized risk factor for cardiovascular morbidity and mortality [1, 3]. In daily practice, the assessment of obesity is based on the simple calculation of body mass index (BMI). However, this measure suffers of some limitations such as the inability to differentiate between lean and fat mass or to identify the body fat distribution [16, 22]. A number of studies have demonstrated that body fat distribution contributes to morbidity and mortality beyond the degree of obesity per se.Indeed, abdominal obesity is more closely associated with risk of morbidity and mortality, while hip circumference has been shown to be inversely associated with cardiovascular disease [6, 20]. To overcome the limitation of BMI, other simple measures of adiposity have been implemented like waist circumference (WC), waist-to-hip ratio (W/HR) and waist-to-height ratio (W/HtR) [2 , 17]. Each of these measures seems to correlate with metabolic and cardiovascular diseases and hemorheological alterations [9 , 29]. In recent years, new measures of body adiposity have been introduced: the Lipid Accumulation Product (LAP), based on waist circumference and triglycerides [15], the Body Adiposity Index (BAI), based on hip circumference and height [5] and the Body Shape Index (ABSI), based on height and weight combination [19]. These indices seem to better associate with common cardiovascular risk factors and mortality than BMI, but data about a possible association with blood rheology are still lacking.

The aim of the present study was to evaluate if LAP, BAI or ABSI better associate with blood and plasma viscosity than “classical” measure of adiposity (WC, W/HR, W/HtR, BMI).

2 Materials and methods

2.1 Subjects and study design

The data in this analysis were drawn from a cross-sectional observational study designed for the prevention of cardiovascular diseases. All participants were adult aged >18 years. As many pathological conditions and many medications can affect blood and plasma viscosity, the following exclusion criteria were used: premenopausal females, cigarette smoking, diabetes, plasma triglycerides >400 mg/dL, and drug use (chronic treatment and any drug in the week before blood withdrawal).

Eligible participants who signed the informed consent were recruited. The protocol was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Ethical Committee.

2.2 Clinical examination and anthropometric measurements

All subjects were examined in the morning, after overnight fasting. They underwent clinical examination and blood sample withdrawal. Systolic (SBP) and diastolic (DBP) blood pressure was measured, on the right arm, after the participant had been resting for at least 5minutes, with a standardized sphygmomanometer. Standing height without shoes was measured to the nearest 0.5 cm. Weight was measured to the nearest 0.1 kg in ordinary street clothes. Cigarette smoking, and ongoing drug therapies were investigated by questionnaire. Hip and waist circumference were measured according to the World Health Organization guidelines.

Measures of adiposity were computed as follows:

BMI = weight (Kg) divided by squared height (m);

W/HR = waist circumference (cm) divided by hip circumference (cm);

W/HtR = waist circumference (cm) divided by height (cm);

BAI = hip circumference (cm) divided by (height (m))^1.5–18;

LAP_for men = (waist circumference [cm] –65)×(triglyceride concentration [mmol/l]);

LAP_for women = (waist circumference [cm] –58)×(triglyceride concentration [mmol/l]);

ABSI = waist circumference (m)/BMI^2/3×height (m)^1/2.

2.3 Laboratory measurements

Fasting blood lipids (total cholesterol, HDL-cholesterol, triglycerides) and glucose were measured with commercially available kits. Subjects having plasma glucose ≥126 mg/dl were recalled to repeat the blood glucose measurement, and if both values ≥126 mg/dl, were classified as diabetics. LDL-cholesterol was calculated according to the Friedewald formula.

2.4 Hemorheological variables measurements

Blood and plasma viscosity were measured within 2 hours from blood withdrawal; the blood specimen was added with heparin (35 IU/mL). Viscosity measurement was performed at 37°C with a cone-plate viscometer (Wells-Brookfield DV-III, Stoughton, U.S.A.) equipped with a cp-40 spindle. Blood viscosity was recorded at different shear rates. In the present manuscript, data obtained at 225 s^–1 are used for the analysis. For plasma viscosity the average of measurements at shear rates of 225 and 90 s^–1 was calculated. The coefficient of variation for blood and plasma viscosity was below 3%. Micro-hematocrit (HT) was measured without correction for plasma trapping. The coefficient of variation for micro-hematocrit was ∼1%.

2.5 Statistical analyses

Statistical analyses were performed by PASW 18.0 (SPSS Inc., Chicago, IL, USA) for Windows. The normality of the distribution was assessed by the Shapiro–Wilk test. All studied variables had normal distribution, except triglycerides, BAI and LAP that were log-transformed before analyses. Student’s t-test or Mann-Whitney test were used, as appropriate, to test the differences between males and females. Pearson or Spearman’s correlation coefficient was used, as appropriate, to test the correlation between continuous variables. Multiple linear regression analyses were performed to evaluate the independent association among adiposity indices and biochemical variables and hemorheological parameters. Statistical significance was set at p < 0.05.

3 Results

A total of 344 subjects were recruited for the present investigation, mainly middle-aged people (mean age was 53.1±8.5 years) with a slight prevalence of males (56%, n = 193).

Table 1 shows clinical and biochemical characteristics and hemorheological variables of the participants divided according to the gender. As expected, men showed a worse metabolic profile than women and higher blood viscosity and hematocrit values (p < 0.001). As for the adiposity indices, men had significantly higher Waist, W/HR, W/HtR, and LAP, but lower BAI values than females. No difference in BMI was observed.

The simple correlation analyses reported in Table 2 show a significant correlation between blood viscosity and BMI (r = 0.16), BAI (r = 0.15), LAP (r = 0.16) in males (Panel a), while only LAP related with blood viscosity in females (r = 0.17) (Panel b). No correlation between plasma viscosity and any adiposity indices was observed except for ABSI in males. Other variables significantly related with BV were: gender (r = 0.51), HDL- (r = –0.24) and LDL-Cholesterol (r = 0.17), triglycerides (r = 0.25), SBP (r = 0.12) and DBP (r = 0.13) (p < 0.05 for all coefficients).

Table 3 shows bivariate correlations among the adiposity indices. They were all highly correlated between them (r coefficients ranging from 0.19 to 0.85; p < 0.001), except BAI vs. LAP and vs. Waist. Similar results were obtained also in the analyses performed separately in men and women.

All adiposity indices and further variables significantly correlated with blood viscosity in simple correlation analysis were entered in a stepwise multiple regression analysis (Table 4). Blood viscosity was used as dependent variable, while lipids, age, gender and adiposity measures were used as independent variables. As shown, only gender, LDL-Cholesterol, and LnLAP were independently related with blood viscosity.

4 Discussion

In the present study we have investigated the association between blood rheology and different indices of body fat. The main finding is that blood viscosity associates with indices of adiposity in a different manner between males and females. However, LAP is the only one to be associated with blood viscosity in both the sexes and in the multiple regression analysis, after adjusting for common cardiovascular risk factors.

Dual-energy X-ray absorptiometry (DEXA) scan is the gold standard to measure body fat mass, but it is expensive and time-consuming [13]. For this reason, surrogate indices based on simple anthropometric parameters have been proposed [2 , 22]. Among these BMI is simple to calculate and widely used, but has a number of drawbacks. Several epidemiological studies support the fact that obesity-associated risks relate to the anatomic region of fat accumulation. Specifically, abdominal fat accumulation is characterized by an increased cardiovascular risk while gluteofemoral fat accumulation seems to play a protective role [20]. In this context BMI is not reliable because it is an indicator of “weight excess” rather than central obesity. Indeed, subjects with the same BMI might have different amount of visceral fat. Measurement of waist circumference seems to be a more accurate measure of central obesity, it is a component of metabolic syndrome and in some investigations it has been demonstrated a stronger predictor of cardiovascular disease [16, 23]. However, waist circumference is unable to distinguish between visceral adipose tissue and abdominal subcutaneous adipose tissue. Furthermore, WC is biased by height; thus, the reliability of WC for central obesity diagnosis is reduced for tall or short subjects [24]. The waist-to-hip and waist-to-height ratio, by correcting WC for hip and height, measure the shape of body distribution regardless of the degree of fat excess [2]. Adjusting a measure of visceral and subcutaneous adiposity (as waist circumference) for a measure of subcutaneous adiposity (as hip circumference) allows obtaining a more precise measure of visceral adipose tissue.

The LAP index, proposed by Kahn, reflects the combined anatomic and physiologic changes associated with lipid over accumulation and it could be associated with highly lipolytic adipose tissue. Furthermore, the use of triglyceride levels in combination with waist circumference, named hypertriglyceridemic waist phenotype, has been shown correlated with endothelial dysfunction and systemic inflammation [10]. The BAI, proposed by Bergman et al. in 2011, combines hip and height measurements and it is validated against dual-energy X-ray absorptiometry scan [5]. The most recent ABSI has been demonstrated able to predict mortality hazard independently of body mass index in a large population of the National Health and Nutrition Examination Survey (NHANES) study [19].

A huge number of studies have compared these indices as predictors of cardiovascular or metabolic diseases but the results have been often conflicting and a clear superiority of an index with respect to another has never been demonstrated [2 , 17].

Several studies have focused on the relationship between body fat composition and blood rheology, but this is the first that investigates the contribution of LAP and BAI. In a previous investigation, Brun et al. demonstrated that WC and BMI were the only determinants of blood viscosity while hematocrit associates only with W/HR.

The blood viscosity is the force that opposes to blood flow in arterial segments, and it is strongly influenced by the amount of red blood cells, their deformability, and the amount of plasma proteins. Alterations of blood viscosity are frequently described in obese subjects and might contribute to the complications observed in this condition such as hypertension and insulin resistance [27].

In our population, similarly to that observed in these studies, blood viscosity relates with BMI. However, in simple correlation analyses, similar associations were observed also for BAI and LAP. Interestingly, BAI inversely relates with blood viscosity. The reason of this finding is easily comprehensible by examining the formula used to compute the BAI. Indeed, it is directly related to hip circumference and inversely proportional to the height. Hip circumference is a protective factor against cardiometabolic diseases. The higher the hip circumference the higher is the BAI and thus lower viscosity.

However, multiple linear regression analyses taking into account age, gender, and blood lipids clearly show that only LAP maintains its predictive power. Since its first appearance, many studies have demonstrated the role of LAP index as predictor of incident hypertension, cardiovascular disease and diabetes. The original point disclosed in our study regards the association between LAP and blood viscosity. This finding provides pathophysiological explanation to the previous observations that linked LAP to an increased cardiovascular morbidity. Indeed, increased adiposity as reflected by LAP leads to increased blood viscosity and thus towards a higher cardiovascular risk. Furthermore, LAP has been demonstrated strongly associated with alanine transaminase levels, and then with non-alcoholic fatty liver disease [14]. This condition is characterized by an impaired hemorheological profile that predisposes to the development of insulin resistance [30].

Overall, these results support previous hypotheses that look at the blood viscosity as the unifying parameter linking risk factors (obesity, hypertension, hyperlipidemia, diabetes) to CVD [26].

LAP index is the only measure that combines a clinical variable, such as WC, and a biochemical variable, such as triglycerides, both related with blood viscosity. While the role of WC as cardiovascular risk factor is recognized, in the last years there has been a renewed interest in triglycerides as additional risk factor for cardiovascular disease and all-cause mortality [21]. Furthermore, increase in serum triglycerides interferes with the normal metabolism of glucose in the muscle, thereby causing a reduced sensitivity to insulin [7]. Probably the combination of clinical and biochemical variables, both strongly related to increased blood viscosity, catches better than simple anthropometric measures the risk of cardiovascular disease.

5 Conclusion

In conclusion, our data suggest that LAP index, a combination of waist circumference and triglycerides, is strongly associated to blood viscosity. This result, along with previous evidence, identifies LAP index as a potential cardiovascular risk marker. In our opinion, the results of the present study have important clinical implications. Indeed, they offer to the clinicians a more reliable index, and easy to calculate, for the assessment of metabolic and cardiovascular risk profile in daily practice. Future studies on larger sample of subjects and other population are needed to establish a threshold value for LAP index, which deserves a more aggressive strategy to reduce cardiovascular risk.

Source of funding

No external funding, apart from the support of the authors’ institution, was available for this study.

Conflict of interests

The authors have no conflict of interests in relation to this research study.

Footnotes

Acknowledgments

None.

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