Sex difference in cardiovascular risk in patients with chronic kidney disease: pooled analysis of four cohort studies

Silvio Borrelli; Carlo Garofalo; Francis B Gabbai; Maria Elena Liberti; Paolo Chiodini; Vittorio Simeon; Luca De Nicola; Roberto Minutolo; Collaborative Study Group on the Conservative Treatment of CKD of the Italian Society of Nephrology

doi:10.1093/ndt/gfad036

Sex difference in cardiovascular risk in patients with chronic kidney disease: pooled analysis of four cohort studies

Nephrol Dial Transplant. 2023 Feb 16:gfad036. doi: 10.1093/ndt/gfad036. Online ahead of print.

Authors

Silvio Borrelli¹, Carlo Garofalo¹, Francis B Gabbai², Maria Elena Liberti¹, Paolo Chiodini³, Vittorio Simeon³, Luca De Nicola¹, Roberto Minutolo¹; Collaborative Study Group on the Conservative Treatment of CKD of the Italian Society of Nephrology

Collaborators

Collaborative Study Group on the Conservative Treatment of CKD of the Italian Society of Nephrology:
L De Nicola, R Minutolo, P Zamboli, C Iodice, S Borrelli, P Chiodini, S Signoriello, C Gallo, G Conte, B Cianciaruso, A Pota, F Nappi, F Avella, B R Di Iorio, V Bellizzi, R Cestaro, V Martignetti, L Morrone, A Lupo, C Abaterusso, C Donadio, M Bonomini, V Sirolli, F Casino, T Lopez, F Detomaso, M Giannattasio, M Virgilio, G Tarantino, C Cristofano, S Tuccillo, S Chimienti, F Petrarulo, V Giancaspro, M Strippoli, E Laraia, M Gallucci, B Gigante, C Lodeserto, D Santese, A Montanaro, R Giordano, A Caglioti, G Fuiano, C Zoccali, G Caridi, M Postorino, V Savica, P Monardo, G Bellinghieri, D Santoro, P Castellino, F Rapisarda, P Fatuzzo, A Messina, A Dal Canton, V Esposito, M Formica, G Segoloni, M Gallieni, F Locatelli, R Tarchini, G Meneghel, L Oldrizzi, M Cossu, S Di Giulio, M Malaguti, F Pizzarelli, G Quintaliani, B Cianciaruso, A Pisani, G Conte, L De Nicola, R Minutolo, R Bonofiglio, G Fuiano, G Grandaliano, G Bellinghieri, D Santoro, R Minutolo, L De Nicola, S Borrelli, P Chiodini, C Garofalo, M E Liberti, G Conte, B Cianciaruso, D Russo, A Pota, V Bellizzi, F Nappi, L De Nicola, M Provenzano, P Chiodini, S Borrelli, C Garofalo, M Pacilio, M E Liberti, A Sagliocca, G Conte, R Minutolo

Affiliations

¹ Division of Nephrology, University of Campania Luigi Vanvitelli, Naples, Italy.
² Department of Medicine, VA San Diego Healthcare System and University of California San Diego Medical School, San Diego, CA, U.S.A.
³ Medical Statistics Unit, University of Campania Luigi Vanvitelli, Naples, Italy.

PMID: 36796825
DOI: 10.1093/ndt/gfad036

Abstract

Background: Progression of chronic kidney disease (CKD) has proven to be faster in men than in women. Whether the same holds true for cardiovascular risk remains ill-defined.

Methods: We conducted a pooled analysis of 4 cohort studies from 40 nephrology clinics in Italy including patients with CKD (estimated GFR<60 ml/min/1.73m2 or higher if proteinuria > 0.15 g/day). The aim was to compare multivariable-adjusted risk (Hazard Ratio, 95% Confidence Interval) of a composite cardiovascular endpoint (cardiovascular death and non-fatal myocardial infarction, congestive heart failure, stroke, revascularization, peripheral vascular disease, and non-traumatic amputation) in women (n = 1 192) versus men (n = 1 635).

Results: At baseline, women had slightly higher systolic blood pressure (SBP) as compared with men (139±19 vs 138±18 mmHg, P = 0.049), lower eGFR (33.4 vs 35.7 mL/min/1.73 m2, P = 0.001) and lower urine protein excretion (0.30 g/day vs 0.45 g/day in men, P < 0.001). Women did not differ from men in age and prevalence of diabetes while having a lower prevalence of cardiovascular disease, left ventricular hypertrophy and smoking habit. During a median follow-up of 4.0 years, 517 fatal and non-fatal cardiovascular events were registered (199 in women and 318 in men). The adjusted risk of cardiovascular events was lower in women (0.73, 0.60-0.89, P = 0.002) than in men; however, the cardiovascular risk advantage of women progressively diminished as SBP (as continuous variable) increased (P for interaction = 0.021). Similar results were obtained when considering SBP categories; when compared to men, women had lower cardiovascular risk for SBP <130 mmHg (0.50, 0.31-0.80; P = 0.004) and between 130-140 mmHg (0.72, 0.53-0.99; P = 0.038), while no difference was observed for SBP>140 mmHg (0.85, 0.64-1.11; P = 0.232).

Conclusions: Higher BP levels abolish the cardiovascular protection seen in female vs male patients with overt CKD. This finding supports the need for higher awareness of hypertensive burden in women with CKD.

Keywords: blood pressure; cardiovascular risk; chronic kidney disease; epidemiology; sex.