Publications

BACKGROUND

Elective bilateral salpingo-oophorectomy (BSO) is routinely performed with hysterectomy for benign conditions despite conflicting data on long-term outcomes.

METHODS

This is a prospective cohort of 25 448 postmenopausal women aged 50 to 79 years enrolled in the Women's Health Initiative Observational Study who had a history of hysterectomy and BSO (n = 14 254 [56.0%]) or hysterectomy with ovarian conservation (n = 11 194 [44.0%]) and no family history of ovarian cancer. Multivariable Cox proportional hazards regression models were used to examine the effect of BSO on incident cardiovascular disease, hip fracture, cancer, and death.

RESULTS

Current or past use of estrogen and/or progestin was common irrespective of BSO status (78.6% of cohort). In multivariable analyses, BSO was not associated with an increased risk of fatal and nonfatal coronary heart disease (hazard ratio, 1.00 [95% confidence interval, 0.85-1.18]), coronary artery bypass graft/percutaneous transluminal coronary angioplasty (0.95 [0.82-1.10]), stroke (1.04 [0.87-1.24]), total cardiovascular disease (0.99 [0.91-1.09]), hip fracture (0.83 [0.63-1.10]), or death (0.98 [0.87-1.10]). Bilateral salpingo-oophorectomy decreased incident ovarian cancer (0.02% in the BSO group; 0.33% in the ovarian conservation group; number needed to treat, 323) during a mean (SD) follow-up of 7.6 (1.6) years, but there were no significant associations for breast, colorectal, or lung cancer.

CONCLUSIONS

In this large prospective cohort study, BSO decreased the risk of ovarian cancer compared with hysterectomy and ovarian conservation, but incident ovarian cancer was rare in both groups. Our findings suggest that BSO may not have an adverse effect on cardiovascular health, hip fracture, cancer, or total mortality compared with hysterectomy and ovarian conservation.

BACKGROUND/AIMS

Reduced kidney function and albuminuria are associated with higher risk for cardiovascular disease (CVD) and mortality in HIV-infected individuals. We investigated whether reduced estimated glomerular filtration rate (eGFR) and albuminuria are associated with subclinical vascular disease, as assessed by carotid intima-medial thickness (cIMT).

METHODS

Cross-sectional analysis of 476 HIV-infected individuals without clinical evidence of CVD enrolled in the Fat Redistribution and Metabolic Change in HIV infection (FRAM) study, using multivariable linear regression. eGFR(Cys) and eGFR(Cr) were calculated from cystatin C and creatinine levels. Albuminuria was defined as a positive urine dipstick (≥ 1+) or urine albumin-to-creatinine ratio ≥ 30 mg/g. Common and internal cIMT were measured by high-resolution B-mode ultrasound.

RESULTS

In unadjusted analyses, eGFR(Cys) and eGFR(Cr) were strongly associated with com- mon and internal cIMT. Each 10 ml/min/1.73 m2 decrease in eGFR(Cys) and eGFR(cr) was associated with a 0.008 mm higher common cIMT (p = 0.003, p = 0.01) and a 0.024 and 0.029 mm higher internal cIMT (p = 0.003), respectively. These associations were eliminated after adjustment for age, gender, and race. Albuminuria showed little association with common or internal cIMT in all models.

CONCLUSIONS

In HIV-infected individuals without prior CVD, reduced kidney function and albuminuria were not independently associated with subclinical vascular disease, as assessed by cIMT. These results suggest that research should focus on searching for novel mechanisms by which kidney disease confers cardiovascular risk in HIV-infected individuals.

Sphingosine kinase (SphK) exhibits two isoforms, SphK1 and SphK2. Both forms catalyze the synthesis of sphingosine 1-phosphate (S1P), a sphingolipid involved in ischemic preconditioning (IPC). Since the ratio of SphK1:SphK2 changes dramatically with aging, it is important to assess the role of SphK2 in IR injury and IPC. Langendorff mouse hearts were subjected to IR (30 min equilibration, 50 min global ischemia, and 40 min reperfusion). IPC consisted of 2 min of ischemia and 2 min of reperfusion for two cycles. At baseline, there were no differences in left ventricular developed pressure (LVDP), ± dP/dtmax, and heart rate between SphK2 null (KO) and wild-type (WT) hearts. In KO hearts, SphK2 activity was undetectable, and SphK1 activity was unchanged compared to WT. Total SphK activity was reduced by 53%. SphK2 KO hearts subjected to IR exhibited significantly more cardiac damage (37 ± 1% infarct size) compared with WT (28 ± 1% infarct size); postischemic recovery of LVDP was lower in KO hearts. IPC exerted cardioprotection in WT hearts. The protective effect of IPC against IR was diminished in KO hearts which had much higher infarction sizes (35 ± 2%) compared to the IPC/IR group in control hearts (12 ± 1%). Western analysis revealed that KO hearts had substantial levels of phosphorylated p38 which could predispose the heart to IR injury. Thus, deletion of the SphK2 gene sensitizes the myocardium to IR injury and diminishes the protective effect of IPC.