Sex difference in cardiovascular risk in patients with chronic kidney disease: pooled analysis of four cohort studies
Authors: Borrelli Silvio , Garofalo Carlo , Gabbai Francis B , Liberti Maria Elena , Chiodini Paolo , Simeon Vittorio , De Nicola Luca , Minutolo Roberto ,   for the Collaborative Study Group on the Conservative Treatment of CKD of the Italian Society of Nephrology, De Nicola L , Minutolo R , Zamboli P , Iodice C , Borrelli S , Chiodini P , Signoriello S , Gallo C , Conte G , Cianciaruso B , Pota A , Nappi F , Avella F , Di Iorio B R , Bellizzi V , Cestaro R , Martignetti V , Morrone L , Lupo A , Abaterusso C , Donadio C , Bonomini M , Sirolli V , Casino F , Lopez T , Detomaso F , Giannattasio M , Virgilio M , Tarantino G , Cristofano C , Tuccillo S , Chimienti S , Petrarulo F , Giancaspro V , Strippoli M , Laraia E , Gallucci M , Gigante B , Lodeserto C , Santese D , Montanaro A , Giordano R , Caglioti A , Fuiano G , Zoccali C , Caridi G , Postorino M , Savica V , Monardo P , Bellinghieri G , Santoro D , Castellino P , Rapisarda F , Fatuzzo P , Messina A , Dal Canton A , Esposito V , Formica M , Segoloni G , Gallieni M , Locatelli F , Tarchini R , Meneghel G , Oldrizzi L , Cossu M , Di Giulio S , Malaguti M , Pizzarelli F , Quintaliani G , Cianciaruso B , Pisani A , Conte G , De Nicola L , Minutolo R , Bonofiglio R , Fuiano G , Grandaliano G , Bellinghieri G , Santoro D , Minutolo R , De Nicola L , Borrelli S , Chiodini P , Garofalo C , Liberti M E , Conte G , Cianciaruso B , Russo D , Pota A , Bellizzi V , Nappi F , De Nicola L , Provenzano M , Chiodini P , Borrelli S , Garofalo C , Pacilio M , Liberti M E , Sagliocca A , Conte G , Minutolo R 
Published: February 2023

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&lt;60 ml/min/1.73m2 or higher if proteinuria &gt; 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 &lt; 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 &lt;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&gt;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.