Inflammatory markers and cardiovascular risks among overweight-obese Emirati women

The prevalence of abdominal obesity among women in UAE is exceptionally high. However, its impact on cardiovascular health has not been adequately investigated. The aims of this study were to investigate: (1) correlations between inflammatory and oxidative biomarkers vs. anthropometric and metabolic measures; (2) rates of dyslipidemia, diabetes, and hypertension and (3) risks of cardiovascular disease. One hundred ten “healthy” overweight/obese Emirati women attending nutrition counselling clinics were randomly recruited. All participants had completed questionnaire, physical examination and laboratory assessment. The participants’ mean ± SD of age, body mass-index, waist circumference were 39 ± 9 years, 34 ± 6 kg/m2 and 100 ± 13 cm respectively. Among the studied women 45 % met diagnostic criteria for metabolic syndrome showing a positive correlation of hsCRP with BMI (p = 0.002), body fat (p = 0.002) and waist circumference (p = 0.018). There was positive correlation of IL-6 with waist circumference (p = 0.019) and adiponectin with HDL (p = 0.007). Prevalence of HDL <1.3 mmol/L or triglycerides ≥1.7 mmol/L were 82 %, dysglycemia 31 %, and hypertension 27 and 37 % of women had either ‘high’ or ‘moderate’ calculated cardiovascular 10-year risk score. The levels of inflammatory and oxidative stress markers were highly prevalent among overweight/obese Emirati women and this may predispose to increasing cardiovascular risks at relatively young age. Thus effective strategies to impact cardiovascular burden and conducting outcome studies assessing the increased risk of cardiovascular disease and addressing obesity prevention among women are urgently needed.

as a cluster of risks that include adiposity, hypertension, dyslipidemia, and diabetes [10].The syndrome is associated with increased oxidative stress, subclinical inflammation, and altered fibrinolysis [11,12]. Its prevalence in this region is exceptionally high [13][14][15]. However, central obesity is not included in most cardiovascular disease risk assessments. The current algorithms are mainly population-based rather than personalized predictions. Risks of cardiovascular disease in the population can be estimated by the "10 years Framingham score" [16] or "tenyear risk for a first atherosclerotic cardiovascular disease event or the Lifetime risk for a first event" [17].
Excess body fat impairs hemodynamic function, disturbs redox homeostasis, and provokes pro-inflammatory responses [18]. Increased cytokine production generates reactive oxygen and nitrogen species from the visceral and subcutaneous fat. Adverse events of this fatdriven cardiometabolic risks include a gradual deterioration in cardiovascular health, which is commonly seen in patients who have metabolic syndrome. In addition, the central obesity-associated inflammatory cascade in metabolic syndrome causes other serious systemic diseases, such as diabetes and atherosclerosis [19,20]. In the study of Acute Coronary Syndrome Patients in the Middle East (6266 patients), the prevalence of low HDL was more common in females than in males [21].
This study aimed primarily at assessing cardiovascular health risks associated with obesity in women in UAE. Its main objective was to highlight urgent needs for prompting strategies that prevent and treat women who have obesity.

Subjects
This cross-sectional study was approved by the Research Ethics Committee of Al Ain Medical District Human Research Ethics Committee. The study complied with the Declaration of Helsinki. They agreed with the informed consent form, written informed consent was obtained from all participants. The participants were overweight or obese women who attended the Ambulatory Health Service (AHS) dietician clinics in Al Ain city of Abu Dhabi Emirate for counselling on weight reduction. Recruitments were random (every third entry on the appointment list) and assessments were performed prior to any weight reduction intervention. The inclusion criteria were women, previously known to be healthy and aged 18 y or older with BMI ≥25 kg/m 2 . The exclusion criteria were women receiving weight-reduction interventions, taking lipid lowering drugs, regular medications (e.g., β-blockers, α-blockers, digoxin, diuretics, aspirin, nitrates, or hormones), having active chronic illness (e.g., rheumatoid arthritis, hyperthyroidism, and inflammatory bowel disease), pregnancy, or unable to give informed consent. Of the 256 women recruited, 110 (43 %) met the eligibility criteria and were enrolled in this cross-sectional (baseline assessment) study. All participants completed the study face-to-face questionnaire and had physical examination and laboratory assessment as shown in Table 1.
Waist circumference was measured with an unstretched tape midpoint between the bottom of the rib cage and the tip of the iliac crest. Weight and height were measured to the nearest 0.1 kg and 0.1 cm, respectively in a standing position without shoes and in light clothing by a digital scale. Body fat and fat-free masses were measured using Tanita body composition analyzer (Tanita Corporation, Tokyo, Japan). Blood pressure was measured on the right arm at rest for ≥5 min. Three consecutive measures were obtained at 1-min intervals with a standard mercury sphygmomanometer with an appropriate cuff size. The average of last two readings was used.

Statistical analyses
The statistical analyses were performed using the SPSS software version 21.0 (SPSS Inc., Chicago, USA) and R-freeware version 3.1.1 on UNIX platform. Continuous variables with normal distribution were expressed as mean ± SD. The Spearman correlation was used as a nonparametric measure of statistical dependence between two variables among women with and without metabolic syndrome. The criterion of statistical significance was p < 0.05 (2-tailed).

Patient characteristics
Demographic, anthropometric, and laboratory findings in all participants are shown in Table 1. Only 16 (15 %) women had a self-reported physical activity ≥150 min/ week. None of the participants reported history of hypertension. Seven (6 %) women reported diabetes which was controlled on life style measures, 8 (7 %) on diet for dyslipidemia, 9 (8 %) polycystic ovary syndrome, and one (1 %) tobacco smoking.

Discussion
The most important findings in this study are the highly prevalent metabolic syndrome and risks of cardiovascular disease among the studied obese women (Tables 2, 4). The excess body fat in these women is shown to provoke significant subclinical inflammation ( Table 3). The level of adiponectin (an adipocyte-derived cytokine, which reduces free fatty acids and promotes lipid metabolism) is found in the current study to negatively correlate with triglyceride level (p = 0.006), positively correlate with HDL (p = 0.007) in women who do not have metabolic syndrome, and negatively correlate with waist circumference in women who have metabolic syndrome (Table 3). This cardioprotective hormone has been known to improve insulin sensitization and ameliorates inflammation and consequently atherogenic processes [24,25]. Despite its important significance, the level of adiponectin is not routinely used in clinical practice and is not yet included in assessing cardiovascular risks.
Low-grade lingering inflammation (e.g., increased levels of TNF-α and IL-6) and protein and lipid oxidation are commonly reported in individuals who have obesity [26,27]. These biochemical alternations accelerate cardiovascular disease [28]. For example, the strong correlation between hsCRP and central obesity shown in the current study (Table 3) is an independent risk factor for future myocardial infarction [28]. The elevated levels of oxidative stress markers are associated with increased hsCRP and are independent of obesity and insulin resistance [29]. Thus, this laboratory determinant is warranted in screening and monitoring patients who have obesity. However, the clinical utility of other inflammatory biomarkers, such as IL-6 and TNF-α requires further outcome studies.
The majority of studied women were deficient of vitamin D (Table 1). A potential link between vitamin D deficiency and cardiovascular disease has been suggested in a cross-sectional study [30]. The data, however, are still insufficient to conclude that low levels of vitamin D independently increase the cardiovascular risk.
Insulin resistance, inflammation, oxidative stress, and other metabolic disorders (e.g., hyperlipidemia) are related disturbances in women with metabolic syndrome [31]. Abdominal obesity is an important predictor of dyslipidemia and T2DM [5][6][7][8]. BMI and waist circumference have been combined with triglycerides and HDL to determine visceral adiposity index, a gender-specific indicator [32]. This determination has a J-shaped relationship with risks of cardiovascular disease as well as all-cause mortality. In the current study, increased waist circumference was found in 94 % of the studied women (Table 1), and it was significantly associated with increased cardio-metabolic and inflammatory biomarkers (Table 3). Reference values for waist circumference are expected to vary among different ethnic groups. The National Cholesterol Education Program (NCEP), World Health Organization (WHO), International Diabetes Federation (IDF), and modified version specific to the people of South Asian origin (ATP III SAS, 2009) may not represent cutoffs suitable for all regions in the world. Population-specific studies are needed to assess the impact of waist circumference on women's health.
Enhanced systemic inflammation and oxidative stress are associated with elevated plasma triglyceride-rich lipoproteins and oxidized lipoprotein(a) phospholipids that underlie cardiovascular risks [33]. These biochemical disturbances are further augmented by the loss of antiinflammatory, anti-oxidative, and atheroprotective properties of HDL and its apolipoproteins. Low HDL is the second important determinant of metabolic syndrome after waist circumference (Table 2). Women who have obesity are more prone to dyslipidemia, mainly increased triglycerides, decreased HDL, and abnormal ratio of  triglycerides to HDL. Low HDL is a strong biomarker of cardiovascular disease, atherogenic dyslipidemia, proinflammatory cytokines, and oxidative stress [21,34]. In the study of Acute Coronary Syndrome Patients in the Middle East (6266 patients), the prevalence of low HDL was more common in females than in males [21]. Obesity is the main culprit for low HDL and optimizing women's healthy lifestyles (e.g., moderate weight loss combined with exercise and smoking cessation) will significantly increase HDL [21]. Thus, comprehensive campaigns are urgently needed to improve female awareness of the serious adverse events of obesity. Moreover, national strategies are needed to facilitate women's healthy lifestyles, such as parks, gym facilities in and out work places, in-door sport activities, and walking tracks in streets. Overcoming cultural barriers to healthy dietary choices and physical activities are important factors in combating obesity in women.

Conclusions
Obesity among women is coupled with several cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes, and subclinical inflammation. Metabolic syndrome is highly prevalent among the studied women who have obesity. Weight reduction and regular exercise are strongly recommended to all overweight women in order to prevent cardiovascular diseases. Outcome studies assessing the increased risk of cardiovascular disease among women who have obesity are urgently needed. Studies addressing obesity prevention are essential.