Women’s Health
Relationship Between Kidney Stones and Risk of Incident Cardiovascular Disease Among Postmenopausal Women Mahsa H. Javadi* Mahsa H Javadi Danielle J Harvey Bernhard Haring Nora Franceschini Peter F. Schnatz John Robbins Patrick L Montine Ramesh Mazhari Janani Rangaswami Lorena Garcia
Background:
Kidney stones have been linked to an increased risk for cardiovascular disease (CVD). The relationship between CVD and kidney stones is influenced by interconnected factors like obesity, diet, and sedentary lifestyle. However, existing data lacked adjustment for a wide range of confounding variables. Also, the role of obesity as a potential effect modifier in this relationship remains unknown.
Objectives:
To evaluate whether self-reported kidney stones are associated with incident CVD (coronary heart disease (CHD) + stroke+ peripheral artery disease (PAD)+ Cause-specific mortality due to CVD) in postmenopausal women in the Women’s Health Initiative (WHI).
Methods:
In a prospective cohort study of 110,960 postmenopausal women ages 50-79 years without CVD at baseline, data from the WHI observational study (OS) and clinical trials (CT) were analyzed to assess the association between kidney stones and incident CVD. Kidney stone status was self-reported at baseline and during follow-up, treated as a time-varying, dichotomous variable (with 5,799 women reporting kidney stones at some point and 105,161 reporting no kidney stones). Incident CVD was identified based on self-reported diagnosis of CVD, centrally or locally adjudicated. At baseline, demographic and health history information were self-reported, while dietary data were collected using a validated food frequency questionnaire. Key covariates included: age, metabolic factors (osteoporosis, diabetes, high cholesterol, body mass index (BMI), and waist circumference, Waist-to-hip Ratio (WHR)), lifestyle risk factors (total energy expended from recreational physical activity, history of alcohol use and smoking), and sociodemographic conditions (race, ethnicity, neighborhood socioeconomic status (NSES), and region of residence).
Two-sample t-tests were applied to compare the means of each continuous variable between participants with and without kidney stones. Chi-square tests were used to compare the two groups on categorical variables. Cox proportional hazards models assessed the association of kidney stone and incident CVD adjusting for potential confounders. Cox regression models was conducted with the following models: Model 1adjusted for age at baseline. Model 2 additionally adjusted for metabolic factors. Model 3 added lifestyle-related risk factors to Model 2; Model 4 additionally included sociodemographic covariates.
Results:
Mean age for all participants was 62.8. Mean WHR differed slightly between groups [0.82 (±0.08) in kidney stone group, 0.79 (±0.08) in no kidney stone group, p<0.0001]. The racial/ethnic distribution was not significantly different between those with and without a history of kidney stones (p= 0.5). Additionally, participants with a history of kidney stones tended to have lower NSES, [73.4 (±8.5) in kidney stone group, 75.2 (±7.3) in no kidney stone group, p<0.0001]. Over a mean follow-up of 16.5 years in the no kidney stone group, 14.4% developed CVD, with the following specific outcomes: 4.83% developed CHD, 4.24% developed stroke, and 0.77% developed PAD. In the kidney stone group, over a mean follow-up of 14.4 years, 14.7% developed CVD, with 5.06% developing CHD, 4.13% developing stroke, and 0.8% developing PAD.
The crude hazard ratio (HR) for incident CVD was 1.21, 95% confidence interval (CI) (1.15, 1.40), p<0.001, and after adjusting for age, metabolic factors, lifestyle risk factors and sociodemographic conditions, the HR was 1.10 with 95% CI of (1.09, 1.17), p=0.007. The crude hazard ratio (HR) for incident CHD was 1.18, [95% CI: (1.06, 1.30), p<0.01] and the multivariable-adjusted HR was 1.08 [95% CI of (1.01,1.15), p=0.05]. The crude hazard ratio (HR) for incident stroke was 1.18, [95% CI (1.06, 1.30), p=0.05] and the multivariable-adjusted HR was 1.07, [95% CI of (1.01,1.21), p=0.06]. The crude hazard ratio (HR) for incident PAD was 1.07, [95% CI (1.01, 1.19), p=0.6] and the multivariable-adjusted HR was 0.96 [95% CI of (0.88, 1.16), p=0.67].
Conclusion:
Kidney stones are associated with an increased risk of CVD, CHD, and stroke in postmenopausal women but not with PAD. Individuals with a history of kidney stones may represent a high-risk group that could be targeted for early lifestyle/behavioral and other CVD-prevention strategies.