Sex Differences in the Incidence of Peripheral Artery Disease in the Chronic Renal Insufficiency Cohort

Abstract

Background To define how the incidence of peripheral arterial disease (PAD) in chronic kidney disease (CKD) differs according to sex and age. Methods and Results The Chronic Renal Insufficiency Cohort (CRIC) is a multi-center, prospective cohort study of CKD participants. Fine and Gray methods were used to determine the cumulative incidence of PAD, defined by an ankle brachial index (ABI) < 0.90 or a confirmed PAD event, with death as a competing event. Adjusted subdistribution hazard ratios from the Fine and Gray model determined the risk of PAD according to sex. A priori, we hypothesized that the relationship between sex and cumulative incidence of PAD differed according to age. The mean age of the 3,174 participants in this study was 56.6 years and consisted of 55% males. Over a median follow-up of 5.9 years, 17.8% developed PAD, 13.0% were lost to followup and 11.1% died. Females had a 1.53-fold greater adjusted PAD risk compared to men (95% CI 1.27-1.84, p<0.001). These sex-related differences in PAD risk also differed by age (p=0.013). Women, compared to men, were at a markedly increased risk for PAD at younger ages; however, at ages greater than 70 years, the risk was similar across both sexes. Older men had a substantially greater PAD risk compared to younger men. In women, PAD risk did not vary with age. Conclusions Females with CKD have a higher PAD risk compared to males at younger ages. There is an important need to improve our understanding of the biological and clinical basis for these differences.

The Relationship Between Renal Artery Stenosis and Degree of Angio Score on the Lower Extremity Peripheral Arterial Disease in Cipto Mangunkusumo Hospital

“…In addition, with increasing age the blood vessels also physiologically will become poor, and their elasticity decreases. 7,8 ANGIO Score is a scoring system to assess the severity of a PAD by looking at the condition of the blood vessels in both legs. In this study, there was also no relationship between ANGIO Score and gender.…”

Multiple exposures to environmental pollutants and oxidative stress: Is there a sex specific risk of developmental complications for fetuses?

“…Epidemiological and clinical studies indicate that the incidence of age-related inflammatory diseases (Candore et al, 2006), autoimmune diseases (Gleicher and Barad, 2007), anxiety disorders (Bekker and van Mens-Verhulst, 2007), stroke (Reeves et al, 2008), neurodegenerative diseases (Puertas et al, 2012;Schrag et al, 2013), and peripheral artery diseases (Wang et al, 2016) differ markedly between men and women. Nevertheless, health research has failed to adequately explore biological differences related to sex in the prevention and treatment of diseases, because the mechanisms underlying the sex differences in pathogenesis are poorly understood.…”

“…In addition, less is known about how fetal organs of male and female respond to oxidative stress induced by environmental pollutants. The implication for human health remains a challenging area of research, because epidemiological and clinical evidence indicate that the onset, incidence, and progression of diseases differ markedly between men and women (Candore et al, 2006;Regitz-Zagrosek et al 2006;Bekker and van Mens-Verhulst, 2007;Gleicher and Barad, 2007;Reeves et al, 2008;Puertas et al, 2012;Schrag et al, 2013;Ouyang et al 2016;Wang et al, 2016), highlighting the need for sex-specific preventive therapies. Of concern is the prenatal inflammatory intrauterine environment that induces placental molecular redox imbalance in a fetal sex-specific manner (Muralimanoharan et al, 2015).…”

Sex Differences in the Ankle Brachial Index Measurement and Interpreting Findings of Sex Differences in Peripheral Artery Disease Burden

“…Wang et al report a higher incidence of PAD in women as compared to men participating in the Chronic Renal Insufficiency Cohort (CRIC), an observational longitudinal study of people age 21 to 74 years with mild to moderate chronic kidney disease (2). Wang et al followed 3,174 CRIC participants (1,427 (45%) women, mean age 56.6 years) who had an ABI ≥ 0.90 and no clinically evident PAD at baseline.…”