3.4 Curves ROC analysis
The AUROC of the ABSI was 0.631 (95% CI, 0.608–0.654) for CAVI ≥ 9, and 0.617 (95% CI, 0.593–0.641) for high baPWV ≥ 15 m/sec. The AUROC of the BMI was 0.414 (95% CI, 0.391–0.436) for CAVI ≥ 9, and 0.497 (95% CI, 0.472–0.521) for high baPWV ≥ 15 m/s. The AUROC of the WC was 0.483 (95% CI, 0.459–0.506) for CAVI ≥ 9, and 0.504 (95% CI, 0.472–0.536) for high baPWV ≥ 15 m/s (Supplementary Figure 1S, http://links.lww.com/MD/C649).
Our study revealed a positive association between ABSI and used vascular structure and function measures. This association was independent of drugs used to treat hypertension, diabetes mellitus, and dyslipidemia, and of the cardiovascular risk factors and lifestyle. These findings suggest that ABSI might be a good anthropometric measurement to predict vascular structure and function in Spanish subjects at intermediate cardiovascular risk.
Some studies found that IMT and increased arterial stiffness are associated with an increased number of cardiovascular events and mortality, both in general population and in diabetic patients.[20,45–48] On the other hand, ABSI is more associated with all-cause mortality and cardiovascular and cancer mortality than are other anthropometric measurements, and it predicts all-cause mortality independently of BMI.[6–8] Therefore, finding an association between ABSI and vascular structure and function may provide new approaches to evaluate the risk of cardiovascular events in people at intermediate cardiovascular risk.
In this study the mean value of CAVI was higher in men, which is in agreement with published data indicating that CAVI increases linearly with age according to the following formulas: CAVI = 5.0 + 0.048 × age (years) in men, and CAVI = 4.8 + 0.045 × age (years) in women, and that the values of CAVI are higher in men than in women (approximately by 0.2, which is equivalent to 4–5 years old).[49–51] We found no sex differences in the median values of baPWV, which is consistent with data published by Tomiyama et al who showed that the effect of age on baPWV is different according to sex category. Prepubertal women have a higher arterial stiffness than men, and this increases after menopause. However, men show a linear increase in arterial stiffness from puberty. This suggests that women have large arteries that are intrinsically more rigid compared with those of men. However, in women of reproductive age, the effects are offset by sex steroids.[53,54]
Therefore, the relationship between ABSI and the analyzed arterial stiffness parameters may be modified by the influence of age and sex upon arterial aging.
Bouchi et al found that increased visceral fat, with a normal weight, is associated with increased arterial stiffness. Kim et al in turn showed that increased visceral fat, with a normal WC, is associated with increased carotid atherosclerosis. Therefore, elevated ABSI values might indicate low skeletal muscle mass with increased visceral adiposity, together implying an accelerated progression of arterial stiffness. In this regard, ABSI could be an important addition to BMI for identifying subjects at intermediate cardiovascular risk and with an increased risk of arterial stiffness.
This study is the first to show that ABSI may be an important marker of IMT and arterial stiffness, assessed by CAVI and baPWV, in a large sample of Spanish subjects at intermediate cardiovascular risk. Moreover, this association is maintained in the analysis of those subjects when grouped by sex and age (>62 years, ≤62 years). The results of this study suggest that the association between ABSI and arterial stiffness is greater beyond the age of 62 years and in men. On the other hand, age is known to influence arterial stiffness—the latter increasing after 60 years of age.[49,52]
We have found 2 studies that analyzed the relationship between ABSI and arterial stiffness, measured by baPWV, in patients with type 2 diabetes mellitus and in Chinese adults. Their results agree with those found in our investigation. ABSI is positively associated with arterial stiffness assessed by baPWV, independently of visceral adiposity.[28,57] A noteworthy aspect of this study is that the association is maintained after adjusting for different lifestyles that could affect the distribution of body fat and nonfat mass, such as exercise, diet, smoking, and alcohol drinking, and act as confounders in the association of ABSI with arterial stiffness.
However, several studies have analyzed the association of other anthropometric measurements (BMI and WC) with arterial stiffness. In the general population without cardiovascular disease,[25–27] carotid femoral pulse wave velocity (cfPWV) showed a moderately positive relationship with WC (correlation coefficient r, 0.16–0.40) and BMI (r, 0.12–0.35). Nevertheless, in the study by Rodrigues et al, when performing multiple regression analysis adjusted for age, mean arterial pressure, and heart rate, BMI showed a negative association (β = −0.103, P = .12), and the observed relationship with WC was lost. Only Strasser et al confirmed the association of these anthropometric measurements with baPWV, obtaining similar results with for (r = 0.26) and BMI (r = 0.23). Studies conducted on diabetic patients[58–61] showed a weaker relationship between cfPWV and anthropometric measurements, obtaining r coefficients between 0.08 and 0.15, both for WC and BMI. Furthermore, in some cases, the relationship with WC or BMI disappeared after adjusting for potential confounders. Finally, the study conducted by Recio-Rodrigues et al in healthy subjects and in hypertensive and diabetic patients concluded that, independently of the presence of diabetes mellitus or hypertension, abdominal obesity correlates better than peripheral obesity with cfPWV and IMT.
This negative association of BMI with CAVI has already been described in previous studies. In a studio realized in 23,257 healthy Japanese subjects showed that after adjusting for confounders, the CAVI correlated negatively with BMI in both sexes (r = −0.119). These findings are consistent with our own observations. Furthermore, this negative correlation has also been reported in other population groups, such as children  and hypertensive and type 2 diabetic patients. Similarly, waist circumference has shown a negative association with CAVI in subjects with metabolic syndrome.[64,65] However, not all studies have found a negative association. Consequently, the relationship between weight gain and arterial stiffness involves complex mechanisms, and vascular adaptation to fat accumulation remains the subject of controversy. Likewise, the physiopathological mechanisms explaining how obesity increases the incidence of cardiovascular disease complementary to the classical risk factors have not been fully clarified. On the other hand, it must be remembered that arterial stiffness depends on arterial wall elasticity and diameter, and a positive correlation has been found between BMI and aortic diameter measured by nuclear magnetic resonance. This could partially explain the negative association of BMI with arterial stiffness.
The results of our study suggest that ABSI is an anthropometric parameter that offers advantages over BMI in the analysis of the association between adiposity and the vascular structure and function measures in subjects with intermediate cardiovascular risk. This could be explained by the fact that ABSI takes BMI, WC, and height into account, mitigating the limitations of these parameters considered separately.[2,5] In our study, ABSI was positively correlated to CAVI and baPWV, while BMI showed a negative correlation to CAVI and no correlation to baPWV. We therefore consider that ABSI is a measure that offers complementary clinical information beyond the mere mathematical effect derived from its calculation, since it shows a direct correlation to the two used stiffness measures, thereby facilitating clinical interpretation.
Our results suggest that the association of arterial stiffness with measures of central obesity (WC) and peripheral obesity (BMI) is unclear both in general population and in patients with diabetes mellitus. Therefore, based on this study, it is necessary to promote new research on large samples, examining various anthropometric measurements and stiffness measures of the central and peripheral vascular system.
In summary, the results of our investigation are novel and may have important clinical relevance, showing the association of ABSI, which includes measures of both general and abdominal obesity, with vascular structure and function in patients at intermediate cardiovascular risk. It also provides information to conduct prospective studies and to analyze whether its use would improve cardiovascular risk equations. Therefore, because it is easy to determine and has a low cost, ABSI can be useful in clinical practice.
The main limitation of our study is its cross-sectional design, which did not allow us to establish causal relations or the direction of the influence of the vascular structural and functional parameters on ABSI and vice versa. Second, the population of this study was ethnically homogeneous (all subjects were Spanish at intermediate cardiovascular risk), and therefore, the extrapolation of our findings may be limited. Another limitation that should be kept in mind is that carotid ultrasound measurements were only performed in 448 subjects.
In conclusion, the results of this study indicate that ABSI is positively associated with vascular structure and function, independently of BMI and other confounders that may influence weight and fat mass distribution in subjects at intermediate cardiovascular risk. Therefore, ABSI, because of easy calculation and low cost, can be a useful clinical tool to detect individuals at high risk of presenting abnormalities in vascular structure and function.
The authors are grateful to all professionals participating in the MARK study.
Lead author of this group: Rafel Ramos, Research Unit, Primary Health Care, Girona, Jordi Gol Institute for Primary Care Research (IDIAP Jordi Gol), Catalonia, Spain
Coordinating persons and centers: Rafel Ramos, Ruth Martí, Dídac Parramon, Anna Ponjoan, Miquel Quesada, Maria Garcia-Gil, Martina Sidera, and Lourdes Camós, Research Unit, Primary Health Care, Jordi Gol Institute for Primary Care Research (IDIAP Jordi Gol), C/Maluquer Salvador, 11, Girona 17002, Catalonia, Spain
Fernando Montesinos, Ignacio Montoya, Carlos López, Anna Agell, Núria Pagès of the Primary Care Services, Girona, Catalan Institute of Health (ICS), Catalonia, Spain
Irina Gil, Anna Maria-Castro of the Primary Care Services, Girona, Institut d’Assistència Sanitaria (IAS), Catalonia, Spain
Fernando Rigo, Guillermo Frontera, Antònia Rotger, Natalia Feuerbach, Susana Pons, Natividad Garcia, John Guillaumet, Micaela Llull, and Mercedes Gutierrez of the Health Center Primary Care San Augustín, Ibsalut Balears, Spain
Cristina Agudo-Conde, Leticia Gómez-Sanchez, Carmen Castaño-Sanchez, Carmela Rodriguez-Martín, Benigna Sanchez-Salgado, Angela de Cabo-Laso, Marta Gómez-Sánchez, Emiliano Rodriguez-Sanchez, Jose Angel Maderuelo-Fernandez, Emilio Ramos-Delgado, Carmen Patino-Alonso, Jose I Recio-Rodriguez, Manuel A Gomez-Marcos, and Luis Garcia-Ortiz, Primary Care Research Unit of The Alamedilla, Castilla and León Health Service (SACYL), Salamanca, Spain
LG-S and MAGG-M prepared the manuscript draft, participated in fund raising and interpretation of results, and corrected the final version of the manuscript. LG-O participated in the study design, interpretation of results, and manuscript review. CA-C, ER-S, and FR participated in data collection and manuscript review. MCP-A and AM performed all analytical methods, interpretation of results, and manuscript review. RR, RM, LG-O, MG-S, and MAG-M participated in the protocol design, fund raising, analysis of results, and final review of the manuscript. All authors reviewed and approved the final version of the manuscript.
Conceptualization: Manuel A Gomez-Marcos, Rafel Ramos, Luis Garcia-Ortiz.
Data curation: Jose I Rodriguez-Sanchez, Fernando Rigo, Rhut Marti, Cristina Agudo-Conde, Rafel Ramos.
Formal analysis: Manuel A Gomez-Marcos, Maria C Patino-Alonso, Luis Garcia-Ortiz.
Funding acquisition: Manuel A Gomez-Marcos, Marta Gomez-Sanchez, Fernando Rigo, Rhut Marti, Rafel Ramos.
Investigation: Manuel A Gomez-Marcos, Leticia Gomez-Sanchez, Marta Gomez-Sanchez, Cristina Agudo-Conde, Rafel Ramos, Emiliano Rodriguez-Sanchez, Jose A Maderuelo-Farnandez, Luis Garcia-Ortiz.
Methodology: Manuel A Gomez-Marcos, Leticia Gomez-Sanchez, Maria C Patino-Alonso, Marta Gomez-Sanchez, Fernando Rigo, Rhut Marti, Rafel Ramos, Emiliano Rodriguez-Sanchez, Jose A Maderuelo-Farnandez, Luis Garcia-Ortiz.
Project administration: Manuel A Gomez-Marcos, Leticia Gomez-Sanchez, Fernando Rigo, Rhut Marti.
Supervision: Manuel A Gomez-Marcos, Leticia Gomez-Sanchez, Maria C Patino-Alonso, Rhut Marti, Cristina Agudo-Conde, Rafel Ramos, Emiliano Rodriguez-Sanchez, Jose A Maderuelo-Farnandez.
Validation: Jose I Rodriguez-Sanchez.
Writing – original draft: Manuel A Gomez-Marcos, Jose I Rodriguez-Sanchez, Emiliano Rodriguez-Sanchez, Jose A Maderuelo-Farnandez, Luis Garcia-Ortiz.
Writing – review & editing: Manuel A Gomez-Marcos, Leticia Gomez-Sanchez, Marta Gomez-Sanchez, Luis Garcia-Ortiz.
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a body shape index; brachial ankle pulse wave velocity; cardio ankle vascular index; carotid intima media thickness; intermediate cardiovascular risk
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