Kidney Stones May Up CHD Risk in Women, But Not Men

July 30, 2013

CHICAGO, Illinois— A history of kidney stones predicts later coronary heart disease (CHD) events in women independently of dietary calcium intake and many cardiovascular risk factors, but the same doesn't seem to be true for men, according to a combined analysis of three large cohort studies[1].

Whether there is indeed a pathophysiologic relationship between nephrolithiasis and CHD events, especially one that varies by sex, remains a mystery, caution the authors, led by Dr Pietro Manuel Ferraro (Catholic University of the Sacred Heart, Rome, Italy). The authors speculate that the link is an "unknown inherent metabolic state" for which kidney stones are an early marker and CHD a later effect, or perhaps they have risk factors in common that were not accounted for in the analysis.

The analysis was published in the July 24/31, 2013 issue of the Journal of the American Medical Association.

The three cohorts comprised 45 748 men and 196 357 women without CHD at baseline who were participants in the Health Professionals Follow-up Study (HPFS; 45 748 men aged 40–75 years), Nurses’ Health Study 1 (NHS 1; 90 235 women aged 30–55 years), and NHS 2 (106 122 women aged 25–42 years).

Kidney stones either before baseline or during follow-up were reported by 8.1% of the combined cohorts. In adjusted analysis, their associated hazard ratios for incident CHD events were "modestly but statistically significantly increased" in the two cohorts of women, but not in the cohort of men.

Hazard Ratiosa (95% CI) for CHD Eventsb Associated With Kidney Stonesc vs No Kidney Stones, by Cohort

End point HPFS NHS 1 NHS 2
Any CHD event 1.06 (0.99–1.13) 1.18 (1.08–1.28) 1.48 (1.23–1.78)
Fatal/nonfatal MI 1.01 (0.92–1.11) 1.23 (1.07–1.41) 1.42 (1.07–1.90)
Revascularization 1.06 (0.98–1.14) 1.20 (1.09–1.32) 1.46 (1.17–1.81)

HPFS=Health Professionals Follow-up Study

NHS 1=Nurses’ Health Study 1

NHS 2=Nurses’ Health Study 2

a. Adjusted for age and race; region of residence; family history of heart disease; diabetes, hypertension, gout, or elevated cholesterol; use of aspirin, thiazide diuretics, loop diuretics, oral steroids, lipid-lowering drugs, calcium-channel blockers, beta-blockers, ACE inhibitors, other antihypertensive drugs; menopausal status and postmenopausal hormone use (for NHS 1 and 2); profession (for HPFS); smoking status; body-mass index; physical activity; intake of calcium, potassium, magnesium, animal protein, total fat, vitamin D, alcohol, and caffeine; and Dietary Approaches to Stop Hypertension score.

b. Follow-up of up to 24 years in men and 18 years in women.

c. Fatal or nonfatal MI, fatal CHD, or revascularization (CABG or PCI).

The authors caution that the findings may not be generalizable beyond the predominantly white HPFS, NHS 1, and NHS 2 populations, noting that "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)." Also missing from the analysis were data on kidney function, which also could have had an effect on outcomes.

The study was supported by the National Institutes of Health. Ferraro had no disclosures. Disclosures for the coauthors are listed in the paper.

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