Increase in Religiosity Over Time is Associated with Reduced Cystatin C Levels Among U.S. Adults

doi:10.21203/rs.3.rs-4618550/v1

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Research Article

Increase in Religiosity Over Time is Associated with Reduced Cystatin C Levels Among U.S. Adults

https://doi.org/10.21203/rs.3.rs-4618550/v1

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Background: Religiosity is associated with better health, yet the underlying mechanism is unclear. Cystatin C is a marker of oxidative stress, vascular dysfunction, and inflammation. We assessed the influence of religiosity on cystatin C levels among participants in the Health and Retirement Study (HRS).

Method: This is a retrospective secondary analysis of the HRS data from 2006 (wave 1), 2010 (wave 2), and 2014 (wave 3), a nationally representative study from the United States. A total of 2,358 participants with complete cases were included in the panel data analysis examining change in religiosity on cystatin C levels. Religiosity and cystatin C were assessed using the Brief Multidimensional Measure of Religiousness/Spirituality scale and serum cystatin C levels, respectively, controlling for covariates.

Results: Approximately 59.1% of the participants were female, 87.4% were white, and 12.6% belonged to other races. The average years of education was 13.2 years. From 2006 to 2014, mean cystatin C levels increased from 1.016mg/L to 1.215mg/L, indicating worsening kidney function over time. In the final model, an increase in religiosity over time was negatively associated with cystatin C levels (B: -0.003, 95% CI: -0.005, -0.001). Higher education (B: -0.011, 95% CI: -0.018, -0.005) and being married (B: -0.039, 95% CI: -0.077, -0.001) were negatively associated with cystatin C levels. In contrast, diagnoses of hypertension (B: 0.094,95% CI: 0.064, 0.125), diabetes (B: 0.109, 95% CI: 0.067, 0.152), and overweight (B=0.072, 95% CI: 0.041, 0.102) were positively associated with cystatin C levels. No observed relationship between sex, race, and cystatin c levels.

Conclusion: Increased religiosity is associated with lower cystatin C levels and may play a role in modulating the course of illnesses to which oxidative stress, vascular dysfunction, or inflammation may contribute. This study will enhance our understanding of how religiosity might influence kidney health and quality of life.

Cystatin C

kidney

mechanisms

religiosity

renal health

Dimensions of religiosity, such as religious beliefs, values, and practices, have been linked to decreased all-cause mortality among adults with chronic kidney disease (CKD) and associated with better health outcomes in persons with CKD [1, 2]. Yet, the underlying mechanisms accounting for these findings are not well understood [3, 4]

Cystatin C, a cysteine protease inhibitor and a marker of renal health, produced and released in most nucleated cells [5] is associated with increased oxidative stress, endothelial and vascular dysfunction [6]^, and inflammation [7]. As such, elevated cystatin C may reflect either a general biomarker of a present disease process or an underlying biological vulnerability that sets the stage for such a process [3, 8]. Elevated cystatin C is an independent marker for increased mortality, cardiovascular diseases such as stroke, coronary artery disease, and peripheral artery disease, as well as cognitive decline [9].

The intricate relationship between religiosity and cystatin C remains an area of ongoing investigation. While the precise mechanisms underlying this association are still being elucidated, accumulating evidence suggests that different dimensions of religiosity may directly or indirectly influence cystatin C levels and kidney function through various mechanisms, including stress reduction, healthy lifestyle promotion, and enhanced coping strategies [10].

This study is informed by Masters’ [11] basic model of religiosity and health, which proposes that religiosity's impact on health is mediated through appraisal, coping mechanisms, and health-related behaviors. According to the model, when individuals encounter stress or adversity, various dimensions of religiosity, such as prayer, meditation, religious attendance, or seeking psychosocial assistance from religious leaders or communities, can lead to the adoption of healthier behaviors. These behaviors include but are not limited to smoking cessation, increased physical activity, improved dietary choices, reduced alcohol consumption, and enhanced medication adherence, all of which have the potential to influence cystatin C levels (Fig. 1).

We sought to determine the relationship between religiosity and mean cystatin C levels over time among participants in the Health and Retirement Study using complete case analysis from 2006 to 2014 while controlling for important health-related and sociodemographic factors. This study informs a potential pathway through which religiosity may influence specific health biomarkers.

Study Design and Population

Publicly available data from the Health and Retirement Study (HRS) were utilized for these analyses. HRS data collection began in 1992 and has been repeated every two years [12, 13]. The HRS is a nationally representative data set of US adults sponsored by the National Institute on Aging (NIA U01AG009740) and the Social Security Administration. It includes cognitive, demographic, economic, family, behavioral, social, and health data that can inform the state of health and other indicators among US adults. Variables of interest from the RAND version of the HRS database and the original HRS variables collected at the household level (called the Fat Files) were merged [14].

The institutional review boards at Duke University Medical Center and The University of Michigan approved the HRS study. Study respondents or their surrogates provided informed consent. A total of 2,358 participants with complete cases from wave 1 to wave 3 of the HRS study were included in the analysis (see the Consort Diagram in Fig. 2 for how the sample was derived).

Measures

Religiosity

Religiosity was measured using the Brief Multidimensional Measure of Religiousness/Spirituality scale [15]. A composite score of religiosity was created using the additive scores of the following four indicators; “I believe in a God who watches over me,” “the events of my life unfold according to a divine or greater plan,” “I try hard to carry my religious beliefs over into all my other dealings in life,” and “I find strength and comfort in my religion.” Responses ranged from 1–6 (strongly disagree to strongly agree). A higher score indicates an increasing level of religiosity [15]. Change in religiosity was calculated by finding the difference between the current and the preceding wave. We focused on change in religiosity to account for the natural fluctuations in participant's religious beliefs and practices over time. Religiosity is not a fixed characteristic; research suggests that dimensions of religiosity such as frequency of religious participation and strength of faith can all change throughout a person's life, and these changes can influence health outcomes [16].

Cystatin C

Trained study phlebotomists from the HRS research team collected venous blood samples with a morning draw from participants in their homes. Bloodspot samples were assayed for cystatin C measured in mg/L using a Siemen’s Dade-Behring BNII nephelometer (Deerfield, IL) at the University of Vermont [17]. Elevated serum cystatin C level is defined as ≥ 1.12 mg/L using the national average in the US among healthy participants as a reference point [18].

Covariates

Participant characteristics include age (middle age 45–65 years, old age: 66 years and older), sex (male, female), education in years (0–17), marital status (married vs not married), race/ethnicity (White/Caucasian, Black/African American, Other), household income, body mass index (BMI). (normal [18.5 kg/m2 and < 25 kg/m2] vs. overweight [≥ 25 kg/m2]), hypertension (0 vs. 1), diabetes (0 vs. 1), and cancer (0 vs 1). Evidence suggests these variables influence cystatin C levels [3, 19, 20]. All covariates included in the analysis were measured in 2006 and 2010 [21].

Statistical Analysis

Panel data modeling was used to examine the effect of religiosity over time on the mean cystatin C levels adjusting for covariates. Specifically, the Generalized Estimating Equation (GEE), a population-level analysis that uses the quasi-likelihood function to produce population-averaged estimates of parameters, was employed to reduce error variance and increase statistical power [22, 23]. The link function in GEE is used to connect the linear predictor to the mean of the response variable. It is expressed as g(µi) = Xiβ, where g is the link function; µi is the expected value or mean of the response variable for the 𝑖-th observation; Xi is the vector of covariates for the 𝑖-th observation and β is the vector of coefficients to be estimated. The identity link function: g(µ)=µ is assumed for our analysis, where the mean of the response is modeled directly as a linear combination of predictors [24].

The analysis exclusively incorporated complete case analysis to reduce potential biases that might arise from missing cases over the study period, thereby strengthening the reliability and validity of the analysis. We performed series of robust checks, including multiple imputations, to reinforce the overall validity of our analysis. Baseline population sample weights were applied to the analysis per recommendation from the HRS documentation. Data were analyzed using the xtgee command in STATA 18. All statistical tests were 2-sided using P < .05 for significance and considering a 95% Confidence Interval.

Of the total number of participants, 59.1% were female, 87.4% were White compared to 12.6% that belonged to other race, and the average years of education was 13.2 years. The percentage of married participants decreased from 71.3–60.8% from 2006 to 2014. Mean household income fell from $73,778 in 2006 to $66,720 in 2010, then rose slightly to $68,548 in 2014. In that same period, there were notable shifts in participants with certain health conditions, including an increase in hypertension (from 51.2–65.2%), diabetes (from 17.9–26.5%), and cancer (from 12–20%). Mean cystatin C levels increased from 1.016mg/L to 1.215mg/L, indicating worsening kidney function. The change in mean religiosity from 2006–2010 was 4.982 but fell to -0.056 between 2010–2014, though it was not statistically significant (Table 1).

Table 1

Descriptive Characteristics of Participants
			2006				2010				2014
Variable	Mean	SD	Min	Max	Mean	SD	Min	Max	Mean	SD	Min	Max
Cystatin C	1.016	0.309	0.28	4.95	1.112	0.409	0.07	5.6	1.215	0.545	0.307	8.86
Change in Religiosity	.	.	.	.	4.982	4.481	-14	21	-0.056	4.765	-20	20
Household Income	73778.69	134787.7	0	5225580	66719.63	73562.14	0	724500	68548.34	88473.41	0	1320356
Education (years)	13.2	2.755	0	17	13.2	2.755	0	17	13.2	2.755	0	17
Age
Middle Age	50.8%		0	1	34.2%		0	1	21.5%		0	1
Old Age	49.2%		0	1	65.8%		0	1	78.5%		0	1
Sex
Male	40.9%		0	1	40.9%		0	1	40.9%		0	1
Female	59.1%		0	1	59.1%		0	1	59.1%		0	1
Race
White/Caucasian	87.4%		0	1	87.4%		0	1	87.4%		0	1
Black/African American	8.9%		0	1	8.9%		0	1	8.9%		0	1
Other	3.7%		0	1	3.7%		0	1	3.7%		0	1
Married
No	28.7%		0	1	33.5%		0	1	39.2%		0	1
Yes	71.3%		0	1	66.5%		0	1	60.8%		0	1
Hypertension
No	48.8%		0	1	40.6%		0	1	34.8%		0	1
Yes	51.2%		0	1	59.4%		0	1	65.2%		0	1
Diabetes
No	82.1%		0	1	76.3%		0	1	73.5%		0	1
Yes	17.9%		0	1	23.7%		0	1	26.5%		0	1
Cancer
No	88.0%		0	1	84.6%		0	1	80.0%		0	1
Yes	12.0%		0	1	15.4%		0	1	20.0%		0	1
BMI
Normal	26.2%		0	1	26.9%		0	1	29.0%		0	1
Overweight	73.8%		0	1	73.1%		0	1	71.0%		0	1
Observations	2358				2358				2358

From Model 1 in Table 2, increase in religiosity over time was negatively associated with cystatin C levels (B: -0.005, 95% CI: -0.007, -0.003). Adjusting for demographic characteristics in Model 2, this negative association persisted (B: -0.004, 95% CI: -0.005, -0.002). Additionally, old age correlated with higher cystatin C levels (B: 0.167, 95% CI: 0.136, 0.199), while higher education (B: -0.015, 95% CI: -0.021, -0.008) and higher income (B: -0.016, 95% CI: -0.028, -0.003) were linked to lower cystatin C levels. However, sex, race, and marital status did not show a significant relationship with cystatin C levels.

Table 2

Association Between Religiosity and Cystatin C (Complete Case Analysis)
VARIABLES	Model 1	Model 2	Model 3
Change in Religiosity	-0.005**	-0.004**	-0.003**
	[-0.007, -0.003]	[-0.005, -0.002]	[-0.005, -0.001]
Age: [Ref: Middle Age]
Old age		0.167**	0.156**
		[0.136, 0.199]	[0.124, 0.187]
Sex: [Ref: Male]		0.014	0.027
Female		[-0.019, 0.047]	[-0.007, 0.059]
Race: [Ref: White/Caucasian]		0.035	0.005
Black/African American		[-0.051, 0.122]	[-0.077, 0.088]
		-0.028	-0.039
Other		[-0.110, 0.054]	[-0.122, 0.042]
		-0.015**	-0.011**
Years of education		[-0.021, -0.008]	[-0.018, -0.005]
Married: [Ref No]
Yes		-0.035	-0.0389*
		[-0.073, 0.003]	[-0.077, -0.001]
Household Income [Log]		-0.0157*	-0.0126
		[-0.028, -0.003]	[-0.025, 0.000]
Hypertension: [Ref: No]
Yes			0.0942**
			[0.0636, 0.125]
Diabetes: [Ref: No]
Yes			0.109**
			[0.0671, 0.152]
Cancer: [Ref: No]
Yes			0.0441
			[-0.004, 0.092]
BMI: [Ref: Normal]
Overweight			0.0717**
			[0.0413, 0.102]
Constant	1.130**	1.448**	1.234**
	[1.110, 1.150]	[1.301, 1.595]	[1.081, 1.386]
Observations	4,716	4,716	4,716
Participants	2,358	2,358	2,358
Wald Chi2	28.05***	256.30***	393.12***
95% confidence intervals in brackets ^ p < 0.05, ^* p < 0.001

In Model 3 of Table 2, which further adjusts for health indicators alongside demographic characteristics, the negative association between increase in religiosity and cystatin C levels remained significant (B: -0.003, 95% CI: -0.005, -0.001). Higher education (B: -0.011, 95% CI: -0.018, -0.005) and being married (B: -0.039, 95% CI: -0.077, -0.001) were negatively associated with cystatin C levels. Conversely, old age (B: 0.156, 95% CI: 0.124, 0.187), diagnoses of hypertension (B: 0.094, 95% CI: 0.064, 0.125), diabetes (B: 0.109, 95% CI: 0.067, 0.152), and being overweight (B: 0.072, 95% CI: 0.041, 0.102) were positively associated with cystatin C levels.

Robust Check

To address missing values, we implemented data imputation, increasing the participant count from 2,385 in the complete case analysis to 4,964 in the imputed dataset. We utilized chained equations for data imputation, applying the multiple imputation command in STATA 18. The findings are detailed in Table 3. Apart from Model 1, similar relationships were observed between change in religiosity and cystatin C levels in Models 2 and 3, both in the imputed and complete case analyses. In line with the complete case findings, an increase in religiosity was negatively associated with cystatin C levels after controlling for demographic factors (Model 2; B: -0.004, 95% CI: -0.005, -0.002) and both demographic and health indicators (Model 3; B: -0.003, 95% CI: -0.005, -0.001), as shown in Table 3.

Table 3

Association Between Religiosity and Cystatin C (Imputation)
	Model 1	Model 2	Model 3
Change in Religiosity	-0.0003	-0.004^***	-0.003^***
	[-0.002,0.001]	[-0.005, -0.002]	[-0.005, -0.001]
Age: (Ref: Middle Age)
Old age		0.217^***	0.201^***
		[0.192, 0.243]	[0.175, 0.226]
Sex: (Ref: Male)
Female		0.001	0.008
		[-0.027, 0.026]	[-0.018, 0.035]
Race: (Ref: White/Caucasian)
Black/African American		0.057	0.024
		[-0.009, 0.122]	[-0.042, 0.089]
Other		-0.0543	-0.070^**
		[-0.117, 0.009]	[-0.134, -0.007]
Years of education		-0.012^***	-0.009^***
		[-0.0176, -0.00594]	[-0.014, -0.003]
Married: (Ref: No)
Yes		-0.029	-0.034^**
		[-0.059, 0.001]	[-0.064, -0.005]
Household Income (Log)		-0.018^***	-0.014^***
		[-0.028, -0.007]	[-0.024, -0.004]
Hypertension: (Ref: No)
Yes			0.101^***
			[0.076, 0.127]
Diabetes: (Ref: No)
Yes			0.150^***
			[0.113, 0.187]
Cancer: (Ref: No)
Yes			0.046^**
			[0.007, 0.085]
BMI: (Ref: Normal)
Overweight			0.0464^***
			[0.020, 0.073]
Constant	1.139^***	1.431^***	1.238^***
	[1.127, 1.150]	[1.319, 1.543]	[1.128, 1.348]
Observations	15,350	8,143	8,143
Participants	7,219	4,964	4,964
F-Statistics	0.32	56.07^***	51.15^***
95% confidence intervals in brackets ^ p < 0.05, ^* p < 0.001

This study examines the relationship between religiosity and mean cystatin C levels among participants in the Health and Retirement Study (HRS) who were followed from 2006 to 2014. The results show that increased religiosity over time is associated with reduced serum cystatin C levels among participants controlling for all other covariates. In addition, an increase in years of education and being married were associated with decreased cystatin C levels. Being overweight and having chronic health conditions such as hypertension and diabetes significantly increased the cystatin C levels during the study period.

Our finding that increased religiosity leads to reduced cystatin c levels is consistent with Suh et al. [25] findings, demonstrating a negative association between cystatin C and religious service attendance (an important dimension of religiosity) over four years among 2,912 U.S. participants. However, our study extends this understanding by encompassing data spanning eight years. To our knowledge, this represents the longest duration of the relationship between religiosity and cystatin C levels among study participants.

The discovery that marriage and higher education are associated with lower cystatin C levels is consistent with prior studies [26]. While there may not be direct evidence explicitly linking higher education and marriage to reduced cystatin C levels, we can speculate how these factors may influence cystatin C based on related studies and known factors. Higher education is often associated with increased health literacy, awareness of healthy lifestyle choices, employment opportunities, socioeconomic status, and reduced stress [27]. Likewise, being married is a strong social determinant of health, often associated with several health benefits, including lower stress levels, better coping mechanisms, and increased social support [28, 29]. Individuals with lower stress levels, as often seen in those with higher education and supportive marriages, may experience reduced cystatin C levels.

The positive relationship between being overweight, having diabetes, having hypertension, and having elevated cystatin c levels is consistent with existing literature [9]. However, it's important to note that the specific impact of diabetes, hypertension, and being overweight on cystatin C levels over an extended period has not been thoroughly explored in the existing literature. This finding addresses that gap by drawing attention to the longitudinal effects of these factors on cystatin C levels.

The finding that increased religiosity leads to lower cystatin C levels suggests religiosity may influence the physiology of individuals with higher religiosity and may play an indirect or direct role in preventing, delaying, or modulating the course of illness for disease processes in which oxidative stress, inflammation, or endothelial cell damage may be a primary cause. For example, individuals with increased religiosity have been shown to have access to coping mechanisms [30] that allow for modulated cognitive appraisals of threat [31, 32] increased perceived internal locus of control [33] and increased social support from one's religious community [34]. These coping mechanisms, in turn, may modulate physiological responses to external stressors thus decreasing overall whole-body stress and inflammatory responses.

In addition to the impact that psychosocial aspects of religiosity may have on core biological processes for individuals with higher religiosity, they may also support engagement in behaviors that allow for increased health or attenuate the impact of current disease states. Studies suggest that individuals with increased religious attendance engage in fewer habits associated with poor health outcomes, including smoking [35] and alcohol use [36, 37]. Because such behaviors directly impact numerous physiological processes, including inflammation and cellular damage, it may be that the effect of religiosity on cystatin C is mediated by the health-enhancing behaviors that are promoted by various religious traditions" OR "is supported by the impact of religiously-endorsed health-related behaviors.

The findings of this study highlight the critical importance of psychosocial determinants of health as a reasonable target for supporting improved health outcomes among U.S. adults. Religiosity may serve as an additional resource for supporting improved health and decreasing overall mortality in patients who find religion important. In addition, the findings of our study are notable as they suggest that there may be a final common biological pathway through which religiosity influences health.

Of note, these findings do not suggest that religiosity alone improves health outcomes. Indeed, numerous aspects of both firmly held religious beliefs and practices are part of a more complex ecosystem in which individuals with a higher religiosity find depth, meaning, and connection to a larger purpose in life. As such, religiosity may not simply be prescribed as an additional measure to improve health outcomes and reduce morbidity. However, for patients for whom religious faith, beliefs, and values are important, recommendations for continued engagement and support for their religious practices and beliefs may positively impact their health. To this end, healthcare providers are encouraged to assess the presence of religious traditions, practices, and beliefs that have been or are currently important to a patient as an additional tool for supporting improved health outcomes [38].

Limitations

This study is limited by potential recall bias due to how religiosity was measured, which could lead to underestimation or overestimation of religiosity and its relationship with cystatin C. Further, the average age for our sample is 69, which is skewed towards older adults. Thus, these findings may not apply to a younger population. Likewise, we acknowledge that multiple factors may contribute to cystatin C that are not accounted for in our analysis or captured in the HRS data, such as inherited kidney disorder, family history of CKD, metabolic syndrome, hepatitis C, and HIV. However, given the large study sample and multiple controlled variables, this study highlights a significant relationship between religiosity and cystatin C, a biomarker of renal health. In addition, the dataset lacked measurements of Glomerular Filtration Rate (GFR), which could elucidate the relationship between cystatin C levels and GFR in the sample.

Implications for Kidney Disease Management

The findings of this study hold significant implications for kidney disease management. First, religiosity for individuals who find religion important may be an effective stress management strategy and coping mechanism, which may buffer against the detrimental effects of stress on kidney function. Religiosity promotes healthier lifestyle choices that may support preventive measures against kidney dysfunction. Second, understanding the relationship between religiosity and kidney health can inform the development of tailored interventions and healthcare approaches that are culturally sensitive and resonate with religious individuals. To that end, culturally sensitive providers can support their patients’ religious beliefs and practices with tailored education, counseling, and treatment plans, potentially enhancing patient engagement and adherence. An important dimension of religiosity is religious communities, which can play a vital role in providing educational resources, organizing support groups, and fostering healthy lifestyle habits among their members. A synergistic collaboration between healthcare providers and religious communities can amplify the impact of kidney disease prevention and management strategies, leading to a paradigm shift in healthcare practices that embrace the holistic dimensions of well-being.

Future Directions

Future studies should explore causal inference between religiosity and cystatin C levels among persons diagnosed with kidney disease. Although the research on religiosity and health outcomes has improved significantly in rigor and design in the last decade, we recommend that researchers continue to employ novel ways to establish a direct relationship between religion and health outcomes. In particular, since randomized controlled trials are impractical for religious measurements [39], longitudinal cohort studies of long duration, with large sample sizes, diverse racial/ethnic and religious populations, and adequate control of potentially confounding covariates are the best option to explore this important variable, we urge both funding agencies and researchers to consider the inclusion of religious assessments and biomarker measurements in longitudinal research endeavors, primarily for two pivotal reasons: promoting holistic health understanding and targeted interventions.

In conclusion, religiosity is associated with improved cystatin C, possibly mediated by health-related behaviors that impact mental well-being, social support, and resilience. Recognizing these multifaceted influences is crucial for understanding how religiosity can contribute to preventing and managing diseases characterized by oxidative stress, inflammation, and endothelial cell damage; and by extension improve quality of life.

Ethical Approval & Consent to Participate

HRS data is publicly available de-identified data which is exempted from University of Pennsylvania IRB review. The HRS study was approved by the Institutional Review Boards at University of Michigan. All methods were carried out in accordance with relevant guidelines and regulations including the Declaration of Helsinki.

Consent for Publication

Not applicable

Availability of data and materials

The data that support the findings of this study are available publicly available at The University of Michigan Health and Retirement Study website: https://hrs.isr.umich.edu/.

Funding & Competing Interest

The authors have no funding or conflict of interest to declare.

Author Contribution

A.C.O.B: Conceptualization; Formal analysis; Methodology; Supervision; Writing – original draft; Writing – review & editing, KCB: Conceptualization; Methodology; Writing – original draft; Writing – review & editing, J.S: Formal analysis; Methodology; Writing – original draft; Writing – review & editing, H.H: Writing – original draft; Writing – review & editing, R.L: Writing – original draft; Writing – review & editing, B.D: Writing – original draft; Writing – review & editing. All authors have read and agreed to the published version of the manuscript.

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Increase in Religiosity Over Time is Associated with Reduced Cystatin C Levels Among U.S. Adults

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Abstract

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Introduction

Literature Review

Methods

Study Design and Population

Measures

Religiosity

Cystatin C

Covariates

Statistical Analysis

Results

Robust Check

Discussion

Limitations

Implications for Kidney Disease Management

Future Directions

Conclusions

Declarations

Ethical Approval & Consent to Participate

Funding & Competing Interest

Author Contribution

References

Additional Declarations

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