Association between Components of Metabolic Syndrome and Rheumatic, Cardiovascular, Gastrointestinal, and Chronic Kidney Disease: A Cross-Sectional Study of Adults in Cyprus

Background of the Study

With the elimination of many of the past infectious diseases, non-communicable diseases have become the main cause of morbidity and mortality, not only in the developed world but also in less developed countries.^[1] This is mainly attributed to the gradual shift of traditional lifestyle and the adoption of a Western lifestyle,^[1] characterized by a diet high in fat and carbohydrates, and a sedentary and physically inactive lifestyle, ultimately leading to overweight or obesity.^[2]

The term “syndrome,” originating from Greek and literally meaning “running together,” refers to a collection of signs or symptoms that occur concurrently.^[3] Metabolic syndrome (MetS) is a cluster of metabolic abnormalities, including centrally distributed obesity, reduced high-density lipoprotein cholesterol (HDL-C), elevated triglycerides, hypertension, and hyperglycemia.^[4] MetS is also known as syndrome X or insulin resistance syndrome.^[5] Various organizations have published different definitions for its diagnosis, such as the World Health Organization (WHO) in 1999, the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) of the USA in 2001, and the International Diabetes Federation (IDF) in 2005, each based on slightly different criteria.^[6]

The prevalence estimates of MetS not only vary between different countries but also within the same country.^[1] This variability occurs due to differences in the applied definition of MetS and is influenced by factors such as ethnicity and the age composition of the study population. In the United States, the age-adjusted prevalence was reported to be 23.9% according to the NCEP ATP III definition and 25.1% according to the WHO definition.^[6] Regardless of the specific definition used, MetS is a commonly occurring condition,^[7] and an improved understanding of MetS could have significant benefits for public health.^[8]

It has been suggested that MetS is associated with cardiovascular disease (CVD), gastrointestinal diseases, rheumatic diseases, as well as chronic kidney disease (CKD).^[9-12] For instance, MetS has been identified as an important risk factor for the incidence and mortality of CVD, with the National Health Service (NHS) in England indicating that hypertension, diabetes, and being overweight or obese are among the primary risk factors for developing CVD.^[9] MetS is also linked to a three-fold increase in type II diabetes (DM2) and a two-fold increase in CVD,^[13] making it a significant contributor to the modern-day epidemics of diabetes and CVD, thereby posing a major public health challenge worldwide.

Furthermore, a review study discussed the association between the individual components of MetS, specifically obesity and abdominal obesity, and gastrointestinal diseases.^[10] The study concluded that obesity, especially visceral obesity, which is the core of MetS, is involved in several gastrointestinal diseases. In addition, individuals with autoimmune rheumatic diseases, such as systemic lupus erythematosus and rheumatoid arthritis, have an increased prevalence of MetS.^[11] Insulin resistance and hyperinsulinemia, which are among the most significant metabolic factors, contribute to the association of MetS with CKD.^[12] However, there is limited research examining the individual components of MetS in relation to all the aforementioned health conditions or diseases.^[14]

According to a cross-sectional study conducted in Cyprus between 2018 and 2019, the most prevalent chronic diseases in Cyprus were diseases of the circulatory system (25%), followed by those of the endocrine system (17%) and the digestive-excretory system (13%).^[15] At the same time, data related to metabolic syndrome in Cyprus are limited. One study suggested that the overall prevalence of MetS was 22.2%, using the National Cholesterol Education Program Adult Treatment Panel III criteria. The study found that the prevalence of MetS increases with age, is higher in men than in women (26.5 vs. 18.3%, respectively), and is higher in rural than in urban areas (26.0 vs. 20.6%, respectively).^[16]

Objectives of the Study

The aim of this study is to investigate the potential association between three components of the MetS (using the IDF definition): Hypertension, elevated fasting plasma glucose or Type II diabetes, and central obesity (defined as body mass index [BMI] >30 kg/m²) with the following conditions: (i) CVD, (ii) gastrointestinal diseases, (iii) rheumatic diseases, and (iv) CKD. The findings of this study have the potential to contribute to the development of targeted health education and intervention programs in Cyprus aimed at addressing these diseases.

Study Variables

A standardized questionnaire was used to collect data from participants and included sections on sociodemographic characteristics, medical history, and lifestyle characteristics. A pilot study was conducted on approximately 10% of the total sample to validate the questionnaire, leading to necessary modifications based on the results. The questionnaire was self-reported, except for the medical history section, which was gathered through a face-to-face interview.

The medical history section included 47 chronic diseases across all human systems (i.e., cardiovascular, digestive/excretory, endocrine, immune, nervous, renal/urinary, reproductive, respiratory, skeletal/muscular systems, and neoplasms). Diseases were coded according to the International Classification of Diseases, 10^th Revision, and information was collected using the question “Have you ever been diagnosed by a physician with any of the following chronic diseases? Choose all that apply.” Cardiovascular diseases include at least one of the following: Angina (I20.9), atrial fibrillation (I48.91), heart failure (I50), and coronary heart disease (I25.1). Similarly, gastrointestinal diseases included at least one of the following: Gastric reflux (K21), irritating bowel syndrome (K58), Crohn’s disease (K50), inflammatory bowel disease/chronic enteritis/ulcerative colitis (K50–K52), and colon cancer (C18.9). Rheumatic diseases included lupus (M32.9) and rheumatoid arthritis (MO6.9). Finally, CKD (N18.9) was also considered.

Sociodemographic characteristics included the age of the participant in years, gender (male/female), and educational status. Educational status was classified into three categories commonly used in Cyprus, namely (i) primary education (participants who completed only primary education - <7 years of schooling); (ii) secondary education (participants who completed middle or high school - 7–12 years of schooling); and (iii) higher education (participants who have a university degree - >12 years of schooling).^[17,18] Weight was reported in kilograms and height in meters. BMI was calculated as weight divided by height squared. According to the WHO classification, obesity was defined as BMI >29.9 kg/m², overweight as BMI 25–29.9 kg/m², normal as BMI 18.5–24.9 kg/m², and underweight as BMI <18.5 kg/m².

Other lifestyle characteristics considered were smoking status and exercise/sedentary activity. The current smokers were defined as those who smoked regularly at the time of the study. In addition, we used definitions from the Centers for Disease Control and Prevention and Behavioral Risk Factor Surveillance System, defining sedentary activity as no physical activity or irregular physical activity reported (i.e., fewer than 3 times/week and/or <20 min/session).^[19] Exercise was categorized as “no” for individuals who did not engage in any kind of exercise and “yes” for those who reported any form of exercise.

The definition of MetS by the IDF was used. According to the definition,^[20] MetS is characterized by the presence of central obesity (defined as increased waist circumference over ethnically specific values) plus any two of the following four factors: (i) Elevated triglycerides (≥150 mg/dL (1.7 mmol/L) or specific treatment for this lipid abnormality), (ii) low high-density lipoprotein cholesterol (<40 mg/dL (1.03 mmol/L) in males and <50 mg/dL (1.29 mmol/L) in females or specific treatment for this lipid abnormality), (iii) high blood pressure (BP) (systolic BP ≥130 or diastolic BP ≥85 mm Hg or treatment of previously diagnosed hypertension), and (iv) elevated fasting plasma glucose (FPG ≥100 mg/dL (5.6 mmol/L), or previously diagnosed Type 2 Diabetes). According to the definition, if FPG is >5.6 mmol/L (>100 mg/dL), the oral glucose tolerance test is strongly recommended, but this is not necessary to define the presence of MetS.

Statistical Analysis

The Shapiro–Wilk normality test was used to examine the normality of the continuous variables. Continuous variables with normal distribution are presented as mean ± standard deviation. Categorical variables are presented as frequency (percentage). Unadjusted logistic regression models were used to check if a covariate was associated with a specific group of diseases and the Wald chi-square test is reported. Subsequently, four multiple logistic regression models were utilized to investigate whether there was an association between the three components of MetS considered (hypertension, DM2, and central obesity) and each group of diseases, after adjusting for possible confounders, namely age, gender, educational status, smoking, exercise, and sedentary activity. All statistical procedures used were conducted using SAS version 9.4 and all tests were two-tailed, performed at an alpha level of significance equal to 0.05.

Potential participants were informed about the study’s aim and their right to withdraw from the study at any time. They were assured that their participation would remain anonymous. In addition, participants were fully briefed on all procedures involved in the study before they provided their consent to participate.

Sociodemographic Characteristics

A total of 1119 participants were included in the study. More than half (56.2%) were females, about 65.1% had completed higher education, and the mean age was 40.6 ± 16.7 years old.

Main Variable (Dependent or Outcome) Results

We observed that approximately 64% of the study participants reported having a sedentary lifestyle, and 35.5% were current smokers. The mean BMI of the participants was 25.0 ± 4.6 kg/m², with approximately 12% classified as obese (BMI >30 kg/m²). Furthermore, when considering the components of MetS, we found that 11.8% of the participants had central obesity, 12.6% had hypertension, and 2.1% had type 2 diabetes [Table 1].

The prevalence of cardiovascular events, gastrointestinal diseases, rheumatic diseases, and CKD was found to be 2.4%, 12.5%, 2.6%, and 1.0% respectively. We observed a statistically significant association between gender and the occurrence of gastrointestinal diseases. Among females, 67.9% had gastrointestinal diseases, while the corresponding percentage among males was 32.1% (p < 00.01) [Table 2].

In univariate analyses, hypertension (p < 0.01), age (p < 0.01), education status (p < 0.01), and exercise (p = 0.03) were statistically significant predictors of cardiovascular events. Similarly, hypertension, age, and gender (all p < 0.01) were statistically significant predictors of gastrointestinal diseases, while hypertension, age, and education status (all p < 0.01, and exercise (p = 0.02) were associated with rheumatic diseases. Furthermore, hypertension, DM2, age, education status (all p < 0.01), and central obesity (p = 0.02) were associated with CKD.

In the multivariate analysis, adjusting for age, gender, educational status, sedentary activity, exercise, and smoking, only age remained a statistically significant predictor of cardiovascular events (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.03–1.09). Similarly, age (OR = 1.04, 95% CI: 1.02–1.05) and gender (OR = 0.50, 95% CI: 0.33–0.75) were statistically significant predictors of gastrointestinal diseases. As for rheumatic diseases, age (OR = 1.06, 95% CI: 1.03–1.09) and gender (OR = 0.34, 95% CI: 0.13–0.84) were found to be statistically significant predictors. However, none of the variables considered in the multivariate analysis showed a significant association with CKD [Table 3].

Strengths and limitations of the study

It is important to acknowledge the limitations of our study. First, we employed a cross-sectional design, which means that we could only examine associations between outcomes and predictors, not establish causal relationships. Furthermore, we did not apply survey weighting, and institutionalized individuals were excluded from the sample, which might have led to an underestimation of the prevalence of the diseases under investigation. Despite these limitations, our study possesses several strengths. It is a large population-based study that employed a representative sample of both men and women across all age groups (18+) and geographical areas of Cyprus. In addition, detailed data were collected from participants, including information on multiple diseases and risk factors, utilizing a validated questionnaire.

Key Messages

1) Hypertension Blood Pressure (BP) appears to play an important role in heart conditions, gastrointestinal diseases, rheumatic diseases, and chronic kidney disease (CKD). 2) Type II diabetes (DM2) and central obesity are associated with CKD and that age and gender are also relevant factors associated with the conditions considered. 3) Countries should develop public health awareness and intervention programs to educate and inform people regarding healthy lifestyles, in general, which will help better cope with these conditions.