Advanced Heart Failure Characteristics and Outcomes in Women and Men.

BACKGROUND: The epidemiology and pathophysiology of heart failure (HF) differ in women and men. Whether these differences extend to the subgroup of patients with advanced HF is not well defined. METHODS AND RESULTS: This is a retrospective cohort study of all adult Olmsted County, Minnesota residents with advanced HF (European Society of Cardiology criteria) from 2007 to 2017. Differences in survival and hospitalization risks in women and men following advanced HF development were examined using Cox proportional hazard regression and Andersen-Gill models, respectively. Of 936 individuals with advanced HF, 417 (44.6%) were women and 519 (55.4%) were men (self-reported sex). Time from development of HF to advanced HF was similar in women and men (median 3.2 versus 3.6 years). Women were older at diagnosis (mean age 79 versus 75 years), less often had coronary disease and hyperlipidemia, but more often had hypertension and depression (P<0.05 for each). Advanced HF with preserved ejection fraction was more prevalent in women than men (60% versus 30%, p<0.001). There were no differences in adjusted risks of all-cause mortality (hazard ratio [HR], 0.89 [95% CI, 0.77-1.03]), cardiovascular mortality (HR, 0.85 [95% CI, 0.70-1.02]), all-cause hospitalizations (HR, 1.04 [95% CI, 0.90-1.20]), or HF hospitalizations (HR, 0.91 [95% CI, 0.75-1.11]) between women and men. However, adjusted cardiovascular mortality was lower in women versus men with advanced HF with reduced ejection fraction (HR, 0.72 [95% CI, 0.56-0.93]). CONCLUSIONS: Women more often present with advanced HF with preserved ejection fraction and men with atherosclerotic disease and advanced HF with reduced ejection fraction. Despite these differences, survival and hospitalization risks are largely comparable in women and men with advanced HF.

The impact of hypoxia preconditioning on mesenchymal stem cells performance in hypertensive kidney disease.

BACKGROUND: Autologous mesenchymal stem cells (MSCs) have emerged as a therapeutic option for many diseases. Hypertensive kidney disease (HKD) might impair MSCs' reparative ability by altering the biomolecular properties, but the characteristics of this impairment are unclear. In our previous pre-clinical studies, we found hypoxic preconditioning (HPC) enhanced angiogenesis and suppressed senescence gene expression. Thus, we hypothesize that HPC would improve human MSCs by enhancing their functionality and angiogenesis, creating an anti-inflammatory and anti-senescence environment. METHODS: MSC samples (n = 12 each) were collected from the abdominal fat of healthy kidney donors (HC), hypertensive patients (HTN), and patients with hypertensive kidney disease (HKD). MSCs were harvested and cultured in Normoxic (20% O2) or Hypoxic (1% O2) conditions. MSC functionality was measured by proliferation assays and cytokine released in conditioned media. Senescence was evaluated by senescence-associated beta-galactosidase (SA-beta-gal) activity. Additionally, transcriptome analysis using RNA-sequencing and quantitative PCR (qPCR) were performed. RESULTS: At baseline, normoxic HTN-MSCs had higher proliferation capacity compared to HC. However, HPC augmented proliferation in HC. HPC did not affect the release of pro-angiogenic protein VEGF, but increased EGF in HC-MSC, and decreased HGF in HC and HKD MSCs. Under HPC, SA-ß-gal activity tended to decrease, particularly in HC group. HPC upregulated mostly the pro-angiogenic and inflammatory genes in HC and HKD and a few senescence genes in HKD. CONCLUSIONS: HPC has a more favorable functional effect on HC- than on HKD-MSC, reflected in increased proliferation and EGF release, and modest decrease in senescence, whereas it has little effect on HTN or HKD MSCs.