A history of kidney stones was associated with an increased risk of coronary heart disease (CHD) in women, but not in men, results of three large prospective cohort studies indicate.

The increased risk ranged from 20% to 50% in two studies, Pierro Manuel Ferraro, MD, of the Department of Internal Medicine and Medical Specialties at Catholic University of the Sacred Heart, and colleagues reported the Journal of the American Medical Association.

They also observed similar increases in risk for fatal and nonfatal myocardial infarction and revascularization in separate analyses. No associations were observed in men from a third large cohort study for either the CHD composite endpoint or individual components.

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“[The] increased risk in women is difficult to explain, even though we could not determine whether this was due to sex or some other difference between the male and female cohorts,” the researchers wrote. “However, differences by sex are not infrequent in studies analyzing the association between nephrolithiasis and either CHD or risk factors for CHD.”

Incidence of kidney stones, or nephrolithiasis, has been on the rise in recent decades. Overall prevalence has increased from 3.8% in 1976 to 1980 to 8.8% in 2007 to 2010. Kidney stones have been linked to systematic diseases, such as hypertension and diabetes, but previous studies examining a possible association with CHD have been inconclusive.

So Ferraro and colleagues analyzed data from three large prospective studies: the Health Professionals Follow-up Study (HPFS), which involved only male participants, and the Nurses’ Health Studies (NHS) I and II, which involved all female participants. Total, the studies included 45,748 men aged 40 to 75, and 196,357 women, aged 30 to 55, without CHD at baseline. Follow up was 18 years for women and 24 years for men.

All three studies were questionnaires focusing on lifestyle and medical history. Incidence of kidney stones was self-reported, but approximately 97% of diagnoses were confirmed in subsequent validation studies.

The researchers defined CHD as a composite of nonfatal or fatal MI, fatal CHD or coronary revascularization procedure. All cases were confirmed in biennial reviews and individual participants’ medical records.

Overall, 19,678 had a history of kidney stones and 16,838 had an incidence of CHD.

After adjusting for confounding factors in NHS I, women with a history of kidney stones had a CHD incidence rate of 754 per 100,000 person years compared with 514 per 100,000 person-years among women without kidney stones. Multivariable analysis resulted in a hazard ratio of 1.18 (95% CI: 1.08-1.28).

Data from NHS II showed CHD incidence rates of 144 versus 55 per 100,000 person years for women with and without a history of kidney stones (HR 1.48, 95% CI: 1.23-1.78).

Men with and without a history of kidney stones had higher rates of CHD compared with women (1,355 versus 1,022 per 100,000 person-years), but the difference failed to achieve statistical significance in a multivariable analysis (HR 1.06, 95% CI: 0.99-1.13).

The researchers noted several trends among participants with kidney stones. These individuals were more likely to have hypertension or use thiazides and in general had lower intakes of calcium, caffeine and vitamin D.

They offered several explanations for the association between kidney stones and CHD. A dietary deficiency, such as low calcium intake, common to both kidney stones and CHD could explain the connection. Renal failure due to kidney stones might worsen CHD cases, whereas an increase in osteopontin levels, common in CHD patients, might lead to the development of kidney stones. They also hypothesized the presence of an unknown inherent metabolic state that may cause both CHD and kidney stones.

Study limitations include lack of generalizability, because the majority of participants were white. “Race has an influence on both nephrolithiasis (with white populations being more prone to form stones compared with black and Hispanic populations) and CHD (with higher incidence among black populations),” the researchers noted.


  1. Ferraro PM et al. JAMA. 2013;310(4):408-415.