Association between chronic kidney disease and cardiovascular disease risk factors in elderly: results from the first phase of Fasa and Shahedieh cohort studies

Abstract

Background

Chronic kidney disease (CKD) is associated with increased cardiovascular disease (CVD) risk factors and morbidity in the elderly population. This study aimed to examine the association between CKD and CVD risk factors in the elderly population of Fasa and Yazd (Shahdieh), Iran, using the data from the enrolment phase of Fasa and Shahedieh cohort studies.

Methods

We conducted a cross-sectional analytical study using data from Fasa and Shahedieh cohort studies, which enrolled 1487 and 1507 participants aged over 60 years, respectively. We collected data on demographic and clinical variables, kidney problems, and CVD from the two studies. We estimated the glomerular filtration rate (eGFR) using the modification of diet in renal disease (MDRD) formula and considered values less than 60 ml/min/1.73 m2 as CKD. We used independent t-tests, Spearman’s correlation coefficient, chi-square, one-way analysis of variance, and logistic regression to analyze the data. We performed the analyses using SPSS V. 22.0 software and set the significance level at 0.05.

Results

The overall prevalence of CKD was 41.9%; 25.7% in women and 16.2% in men. The prevalence of CKD based on reported kidney problems was 1.7%, of which 54.7% were in stage 3 of CKD. Compared to participants in the early stages of CKD, participants in advanced stages had a higher prevalence of diabetes (p < 0.001), hypertension (p < 0.001), ischemic heart disease (IHD) (p < 0.001), and myocardial infarction (p < 0.001). In addition, participants in higher stages of CKD were more obese, had lower physical activity, smoked more, and consumed more opium (p < 0.001).

Conclusion

Our study showed that more than half of the patients were in stage three CKD, which is an advanced stage of this disease. Diabetes Melitus, hypertension, dyslipidemia, IHD, and myocardial infarction were more prevalent in patients than others. These findings demonstrate the importance of screening for CKD in patients with diabetes mellitus and hypertension. The results also suggest that lifestyle modification and prevention strategies are needed to reduce the burden of CKD and CVD in this population.

Background

Chronic kidney disease (CKD) is defined as a systemic pathology that affects approximately 10% of the general population globally [1] and approximately 15% of the general population in Iran [2]. According to the global burden of disease (GBD) 2020, CKD is the 12th leading cause of death in the world in 2017 [3].

CKD is a progressive disease that reduces kidney function [4]. Since one of the factors related to the exacerbation of symptoms, mortality and length of hospitalization and treatment costs in cardiovascular disease (CVD) patients is the reduction of kidney function [5,6,7,8,9]; achieving preventive and interventional strategies for managing CKD patients is very important and necessary.

It should be noted that very high cardiovascular risk (CVR) according to SCORE has been found in 77.51% of the population with CKD [10]. Many studies have shown a high prevalence of CVD among CKD patients. Prevalence of CVD in CKD in China was 9.8%, Japan was 26.8%, USA was 33.4%, Denmark was 29.0% and Brazil was 31.0% [11,12,13,14,15]. In addition, major adverse cardiovascular events (MACEs), which are major causes of mortality in the general population, are common in patients with CKD [16, 17].

CKD and CVD have several common risk factors such as smoking, body mass index (BMI), hypertension, diabetes mellitus, dyslipidemia [18, 19], metabolic syndrome [20] and diet [21] and old age predicts CVD and CKD [21]. According to the results of the studies, 11% of people over 65 without hypertension and diabetes have high creatinine levels, which are in the third stage of CKD [22] and also elderly patients with CKD are at a higher risk of death than their younger peers. and with a decrease in eGFR, the mortality rate due to cardiovascular diseases in the elderly increases [23, 24].

In classic and common studies, chronic kidney disease is not considered as a risk factor for cardiovascular diseases. Also, most of the studies in this field have been conducted abroad and on the general population, while the Iranian elderly population is different from other populations in terms of all the risk factors of heart diseases and chronic kidney disease. Considering the increase in the country’s elderly population and some of them suffering from cardiovascular diseases and kidney diseases and imposing extremely high costs of these diseases on the health care system, the diagnosis of the relationship between CKD along with correct assessment of cardiovascular risk in order to reduce health care costs and mortality rates and identifying educational needs in the field self-care based on problems and needs elderly are very important and necessary. Therefore, the aim of this study was to investigate the relationship between chronic kidney disease and cardiovascular diseases risk factors in elderly population of Fasa and Yazd.

Methods

Study population

In this study, data from the initial phase of the Fasa and Shahedieh cohort studies were utilized, focusing on recorded information from elderly individuals aged 60 years and above. The PERSIAN cohort study, initiated in 2015, aims to include 180,000 Iranians aged 35 and older from 18 distinct geographical regions of Iran. For this investigation, information was extracted from the cohort centers of Fasa and Shahedieh- Yazd [25,26,27].

The study’s inclusion criteria encompassed individuals meeting the following conditions: (1) age over 60, (2) residency in the designated area with Iranian citizenship, and (3) possession of a national card and birth certificate. Conversely, exclusion criteria included: (1) individuals unable to communicate effectively (e.g., deaf, blind, mute, paralyzed), those with acute-stage diseases such as psychosis, and those without appropriate medical records, (2) individuals who had migrated within the last year, and (3) individuals residing in the locations for less than four months annually.

In the PERSIAN cohort study, individuals aged 35 and above were included using a multi-stage cluster sampling method. In contrast, the present study selected all elderly participants aged 60 and above from the target population, resulting in a total of 2,994 participants.

Ethics: Informed consents were obtained through written consent forms. The Fasa cohort study (FACS) protocol was approved with the ethics code (IR.FUMS.RES.1394.3), the Shahdieh cohort study with the ethics code (IR.SSU.RES.1397.135), and this study by the ethics committee of Shahid Sadougi University of Medical Sciences with the ethics code (IR.SSU.SPH.RES.1401.051).

Data collection: The PERSIAN cohort questionnaire, comprising 482 items in three main sections (general, medical, and nutritional), covers living conditions, personal and health issues, and economic and social status. No validity and reliability assessment were deemed necessary [26].

Socioeconomic status: The questionnaire for assessing socioeconomic status includes 15 questions covering housing type and size, number of bedrooms and occupants, means of living, non-curricular books ownership, and travel history. Principal component analysis (PCA) with an assets index variable was employed to calculate the SES score, categorized as low, average, and high SES.

Physical activity measurement: The standard physical activity questionnaire (IPAQ) assessed participants’ activity levels, categorized as light (< 3 METs), moderate (3–6 METs), and vigorous (> 6 METs) physical activity.

Anthropometric indices: US National Institutes of Health protocols [26] measured height, weight, waist, hip, and wrist circumferences, with BMI classifications for the elderly group as underweight (< 19 kg/m2), normal (19–25 kg/m2), overweight (25–30 kg/m2), and obese (> 30 kg/m2).

Blood pressure measurement: Blood pressure was measured twice with a 15-minute interval, and clinical tests were determined after 12 h of fasting [25].

Cardiovascular Rrisk Ffactors Definition: Diabetes mellitus, hypertension, and dyslipidemia were defined based on specific criteria. Diabetes mellitus was defined as either fasting glucose ≥ 7.0 mmol/L, or HbA1c ≥ 6.5%, or use of insulin or oral anti-diabetic medications, or self-reported history of diabetes [28]. Hypertension was defined as either systolic BP > 140 mmHg, or diastolic BP > 90 mmHg, or use of antihypertensive medications, or self-reported history of hypertension [29]. Dyslipidemia was defined as either serum triglyceride level ≥ 150 mg/dL, or use of antihyperlipidemic drugs, or self-reported history of hyperlipidemia [28].

eGFR calculation and CKD stages determination: The modification of diet in renal disease (MDRD) equation was used to calculate the estimated glomerular filtration rate (eGFR), as recommended by the National Kidney Foundation (NKF). The Kidney Disease Outcomes Quality Initiative (KDOQI) clinical guidelines define CKD stage 1 as eGFR ≥ 90 mL/min/1.73 m2 with evidence of kidney damage; stage 2 as eGFR 60–89 mL/min/1.73 m2; stage 3 as eGFR 30–59 mL/min/1.73 m2; stage 4 as eGFR 15–29 mL/min/1.73 m2; and stage 5 as eGFR ≤ 15 mL/min/1.73 m2. In this study, we considered eGFR ≤ 60 mL/min/1.73m2 as CKD (stages 3 to 5) [28].

Statistical analysis: Data analysis involved independent t-tests, Spearman’s correlation coefficient, chi-square test, one-way analysis of variance, and logistic regression, conducted using SPSS version 22.0 with a significance level of 0.05.

Results

A total of 2,994 participants aged 60years and above, with an average age of 63.9 ± 3.0 years, were included. The study compared the Fasa and Shahedieh cohorts, revealing differences in education level, gender distribution, SES, and various health parameters. Notably, the prevalence rates of diabetes mellitus, hypertension, and CKD varied between the two cohorts. The prevalence rate of CKD based on eGFR was 60.5% in Yazd and 23.3% in Fasa (p < 0.001). In this study, 41.98% (1257 participants) had CKD based on eGFR, while the prevalence rate of kidney failure based on self-reported kidney problems in the Fasa and Yazd cohorts was 1.7% (53 participants) (Table 1).

Table 1 Comparison of baseline characteristics of participants and traditional cardiovascular risk factors across Fasa and Shahedieh cohort studies 2015–2016

Participants from the two cohorts were categorized into five stages of chronic kidney disease (CKD) based on their calculated estimated glomerular filtration rate (eGFR). The distribution across stages was as follows: stage 1 CKD − 115 individuals (3.8%), stage 2 CKD − 1622 individuals (54.1%), stage 3 CKD − 1234 individuals (41.2%), and stages 4 and 5 CKD − 21 individuals (0.7%).

It is noteworthy that due to the limited representation of elderly individuals in stage 5 CKD (only one person), the counts for stages 4 and 5 were merged for analysis purposes. In this study, stages 3 to 5 were collectively considered as CKD. Consequently, the overall prevalence of CKD, based on the eGFR index, was 41.9% (1257 individuals).

Table 2 provides an overview of the demographic and clinical characteristics of all study participants categorized by the eGFR index. Individuals in stages 3, 4, and 5 of CKD were found to be older and exhibited higher levels of cholesterol, triglycerides, pulse rate, blood urea nitrogen (BUN), and creatinine, along with lower levels of diastolic blood pressure (p < 0.001).

In comparison to the earlier stages of CKD, individuals in stages 3, 4, and 5 were more likely to be women. The prevalence of CKD, based on the eGFR index, was higher in female patients (50.6%) than in male patients (33.4%). Additionally, the prevalence of CKD was higher among married individuals and those with a middle socio-economic status (p < 0.001).

Table 2 Demographic and clinical characteristics of different groups of participants, according to eGFR

Table 3 illustrates the prevalence of traditional risk factors among participants categorized by the eGFR index. Individuals in advanced stages of chronic kidney disease (CKD) exhibited a higher prevalence of diabetes, hypertension, ischemic heart disease (IHD), and myocardial infarction compared to those in the early stages of CKD (p < 0.001 for all comparisons). Furthermore, individuals in higher stages of CKD were more likely to be obese, physically inactive, smokers, and opium users (p < 0.001 for all comparisons).

Table 3 Prevalence of traditional cardiovascular risk factors in different groups of participants, according to eGFR

In the multivariate analysis, a significant association was observed between chronic kidney disease (CKD) and several variables, including age, gender, city, education level, socioeconomic status, triglycerides, fasting blood sugar (FBS), hypertension, ischemic heart disease (IHD), and METS (Table 4). Specifically, women exhibited approximately 2.4 times the risk of CKD compared to men (OR = 2.4, 95% CI: 1.9–3.0). The risk of CKD in the elderly residing in Yazd was 5 times higher than in those in Fasa (OR = 5.1, 95% CI: 2.2–8). Additionally, individuals with poor socioeconomic status faced a 1.1 times higher risk of CKD than those with good socioeconomic status (OR = 1.2, 95% CI: 1.04–1.4).

Furthermore, the risk of CKD was approximately 2 times lower in individuals engaging in intense physical activity compared to those with low physical activity (OR = 1.3, 95% CI : 1.5–2.8). Individuals with hypertension had a 1.3 times higher risk of CKD than those without hypertension (OR = 1.3, 95% CI: 1.1–1.6). Similarly, individuals with a history of ischemic heart disease (IHD) had a 1.3 times higher risk of CKD than those without a history of IHD (OR = 2, 95% CI: 1.0–1.72).

In the multivariate analysis, a significant relationship was also found between kidney failure (self-reported) and pulse rate (P < 0.05) and MET (P < 0.001). The risk of kidney failure (self-reported) was approximately 0.2 times higher in individuals with less physical activity compared to those with regular physical activity (95% CI = 0.1–0.5).

Table 4 Multiple logistic regression analysis of predictors including cardiovascular risk factors and demographics on CKD*

Discussion

This study explored the impact of cardiovascular disease risk factors on chronic kidney disease (CKD) in individuals aged 60 and above in elderly participants of Fasa and Shahedieh cohort studies. The findings revealed a CKD prevalence of 41.9%, with 25.7% among women and 16.2% among men. The prevalence based on the estimated glomerular filtration rate (eGFR) index was 60.5% in Shahedieh study and 23.3% in Fasa study. Table 1 highlights factors contributing to this difference, including age, gender, lifestyle, physical activity, and cardiovascular risk factors. Notably, the prevalence of CKD in Iran varies widely across studies, such as 31% in Fars [30] province and 35.928.24% in Ilam. Provinces [31]. A noteworthy discovery is the disparity between self-reported CKD (1.7%) and CKD based on the eGFR index (41.9%). More than half of the patients were in stage 3 CKD, an advanced stage. This discrepancy may stem from factors like lack of awareness, underreporting by the elderly, and insufficient communication from medical staff. The study underscores the importance of timely, valid, and quality health information, advocating for information therapy to enhance patient education and self-care.

Our findings align with previous studies indicating associations between lower eGFR and older age, female sex, lower education level, and a history of hypertension [32]. Cardiovascular risk factors like diabetes, hypertension, dyslipidemia, tobacco smoking, obesity, age, diastolic blood pressure, and pulse rate were significantly associated with a decline in eGFR [5, 7, 9, 18, 19, 21, 23, 31, 32]. The study revealed that obese, overweight, and sedentary participants were more likely to be in stages 2 and 3 of CKD, and CKD prevalence was higher in individuals with diabetes, hypertension, dyslipidemia, ischemic heart disease, and myocardial infarction.

Interestingly, our study differs from some prior research by identifying smoking and diabetes mellitus as risk factors for CKD [7, 23]. The prevalence of diabetes is expected to rise, particularly among the elderly, contributing to an increased risk of CKD [9]. Despite some limitations, including the cross-sectional nature of the data and the absence of information on albuminuria and cystatin C, the study’s strengths include a sizable participant pool, comprehensive risk factor and medical condition data, and standardized data collection methods and laboratory tests.

In conclusion, with the rising prevalence of CKD risk factors in aging populations, there is a heightened need for community-based educational programs targeting the elderly. Such initiatives could play a crucial role in preventive and interventional strategies to manage CKD in these communities. Future research should explore the influence of metabolic syndrome and insulin resistance on CKD prevalence in these regions.