Cystatin C and risk of heart failure in the Physicians' Health Study (PHS).
BACKGROUND
Chronic kidney disease is a risk factor for heart failure (HF). Although cystatin C can detect early kidney dysfunction, limited data are available on the association between cystatin C and HF.


METHODS
In a prospective nested case-control study design, we examined whether cystatin C is associated with an increased risk of HF in the PHS and whether such an association is stronger in hypertensive subjects. We selected 220 cases of incident HF and 220 controls, matched on age, year of birth, and time of blood collection. Plasma cystatin C was measured using an immunonephelometry method. We used conditional logistic regression to estimate relative risks (RRs).


RESULTS
Compared with the lowest tertile, the multivariable adjusted RR (95% CI) for HF was 1.15 (0.69-1.89) and 1.78 (1.01-3.13) for the second and third tertiles of cystatin C, respectively. Additional adjustment for systolic blood pressure and history of hypertension attenuated this association (RR = 1.0, 1.23 [0.73-2.09], and 1.61 [0.90-2.88] from the lowest to the highest tertile, respectively). Furthermore, we observed a 4-fold increased risk of HF in the second and third tertiles of cystatin C among hypertensive individuals and no meaningful effects of cystatin C on HF among nonhypertensive subjects.


CONCLUSIONS
Our data demonstrated that higher levels of cystatin C are associated with an increased risk of HF and that such association may be limited to hypertensive individuals. Additional studies are warranted to further examine the relationship between hypertension and cystatin C on the risk of HF.
Djoussé
Luc
L
Department of Medicine, Division of Aging, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02120, USA. ldjousse@rics.bwh.harvard.edu
Kurth
Tobias
T
Gaziano
J Michael
JM
D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D055316:Cystatin C; D015891:Cystatins / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006333:Heart Failure / Q000097:blood* / Q000453:epidemiology* / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology; D015994:Incidence; D007677:Kidney Function Tests; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010820:Physicians; D010865:Pilot Projects; D011336:Probability; D011379:Prognosis; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D017678:Sex Distribution
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins