Citations

<a name=“OLE_LINK2”></a><a name=“OLE_LINK1”>Hypertensive pregnancy (HP) disorders have been linked to a four‐fold increased risk for development of future cardiovascular diseases. We examined whether history of HP in postmenopausal women (N=20, 59±5 yr) influenced the risk factors for cardiovascular disease as assessed by aortic pulse wave characteristics, compared to age and parity matched controls (N=18, 60±4 yr). Non‐invasive aortic pressure waveforms were synthesized from high‐fidelity pressure waveforms obtained from SphygmoCor applanation tonometry using the radial artery. Aortic systolic and diastolic blood pressure (ASBP, ADBP), aortic augmentation index (AI x ), augmented pressure (AP), aortic pulse pressure (APP), and left ventricular wasted energy (E w ) were calculated from the generated aortic pressure waveform. There were no differences in ASBP (125±4 vs. 129±4 mmHg), ADBP (79±2 vs. 81±2 mmHg), AP (17±2 vs. 17±2 mmHg), AI x (35±2 vs. 29±1%), AI x @75BPM (31±2 vs. 29±1%), E w (3313±338 vs. 3364±432 dynes/cm 2 /s), between women with a history of HP vs. matched controls, respectively (P>0.05 for all). Body mass index was significantly higher in women with a history of HP (30.6±1 vs. 26.7±1 kg/m 2 , P<0.05), however it did not statistically influence any of the indices (P>0.05 for all). Our results suggest that postmenopausal women with a history of HP do not demonstrate elevated aortic blood pressure or altered aortic pulse wave characteristics in comparison to matched controls. </a> Supported by: National Institute of Aging 1P50AG044170‐01 and CTSA UL1 TR000135 and HL 118154

β‐adrenergic receptor activation causes a substantial portion of hypoxic vasodilation at rest and during forearm exercise. Recent evidence suggests that β‐receptors are either more sensitive or upregulated in young women vs. men. Therefore, we examined whether sex influences hypoxic vasodilation in 31 subjects (15F/16M; 26± 1 yr). We also examined whether potential sex related differences existed in a group of older adults (6F/5M; 61± 2 yr). All subjects performed forearm exercise at 10% and 20% of maximum under normoxic and hypoxic (80% arterial O2 saturation) conditions. Forearm vascular conductance (FVC; ml/min/100 mmHg) was calculated from blood flow (ml/min) and blood pressure (mmHg). At rest young females demonstrated a greater vasodilator response to hypoxia compared to men (39 ± 12% vs. 13 ± 6%, P < 0.05). The compensatory vasodilator response to hypoxia exercise (% change in ΔFVC compared to respective normoxic exercise trial) was also greater in young womenat 10% (46 ± 8% vs. 29 ± 5%, P < 0.05) and 20% exercise (38 ± 6% vs. 23 ± 4%, P < 0.05). Interestingly the compensatory vasodilator responses between older women and men were similar at 10% (28 ± 6% vs. 28 ± 10%, P = 0.99) and 20% exercise (13 ± 6% vs. 15 ± 7%, P = 0.84), respectively. Our data suggest that the compensatory vasodilator response to hypoxic exercise is greater in young women compared to men. However, sex specific differences appear to be lost with aging.

We examined the relationship between total peripheral resistance (TPR) and central artery pressure and indices of wave reflection in 16 subjects (10F/6M; 26 ± 1 yr). Non‐invasive aortic pressure waveforms were synthesized from high‐fidelity radial pressure waveforms obtained from applanation tonometry of the radial artery. Radial blood pressure (BP) was calibrated from brachial artery BP (catheter). Central artery pressures, aortic augmentation index (AI a ), roundtrip travel time of the reflected wave to and from the periphery (Δt p ; inverse of pulse wave velocity), and wasted left ventricular energy (E w ) were calculated from the generated aortic pressure waveform. Cardiac output (CO) was measured using an open‐circuit acetylene uptake technique and used to calculate total peripheral resistance (mean arterial pressure/CO). TPR was positively related to aortic pulse pressure (r = 0.49), augmented pressure of the central artery wave (r = 0.60), pulse pressure amplification (r =0.54), AI a (r = 0.53), and E w (r = 0.66), (P < 0.05 for all). Additionally, TPR was inversely related to Δt p (r = − 0.51, P < 0.05). Our data suggests that increased levels of TPR are related to measures of central artery pressure, wave reflection characteristics and indices of central artery stiffness. Supported by NIH K23 DK‐082424 (TBC), AHA 2170087(ECH) and CTSA RR‐024150

Abstract Elite performing men continue to record faster record times in running events compared to women. These sex‐based differences in running speed and endurance in humans are expected based on sexual dimorphisms that contribute to differences in the determinants of aerobic performance. Comparatively, the sexual dimorphisms contributing to sex‐based differences in elite aerobic performance are not ubiquitous across other species that compete in running events. The purpose of this review is to offer a framework and model for ongoing discussions of the physiological determinants and ultimately limits of physical performance. The records for average running speed of champion athletes were delineated by sex for thoroughbred horses, greyhound dogs, and humans. Male and female performances within each of these species are being optimized by training, nutrition, and financial incentives, and are approaching a performance maximum. For horses and greyhounds breeding also plays a role. Analysis of athletic records shows that there is a sex‐related difference of ~10% or more in elite athletic performance for humans; however, the upper limit of performance does not appear to be different between sexes for thoroughbred horses and greyhound dogs. In the context of the nil sex differences in running performance in thoroughbreds and greyhounds, we discuss the physiological role of sexual dimorphisms on sex‐specific limits to running performance. We highlight that studies on both human and animal performance in athletic events stimulate critical physiological questions and drive novel research.

Abstract High alcohol intake and breast density increase breast cancer (BC) risk, but their interrelationship is unknown. We examined whether volumetric density modifies and/or mediates the alcohol-BC association. BC cases (n = 2233) diagnosed from 2006 to 2013 in the San Francisco Bay area had screening mammograms 6 or more months before diagnosis; controls (n = 4562) were matched on age, mammogram date, race or ethnicity, facility, and mammography machine. Logistic regression was used to estimate alcohol-BC associations adjusted for age, body mass index, and menopause; interaction terms assessed modification. Percent mediation was quantified as the ratio of log (odds ratios [ORs]) from models with and without density measures. Alcohol consumption was associated with increased BC risk (2-sided Ptrend = .004), as were volumetric percent density (OR = 1.45 per SD, 95% confidence interval [CI] = 1.36 to 1.56) and dense volume (OR = 1.30, 95% CI = 1.24 to 1.37). Breast density did not modify the alcohol-BC association (2-sided P &gt; .10 for all). Dense volume mediated 25.0% (95% CI = 5.5% to 44.4%) of the alcohol-BC association (2-sided P = .01), suggesting alcohol may partially increase BC risk by increasing fibroglandular tissue.

Abstract Introduction Elevated mammographic density (MD) is a strong and independent risk factor for breast cancer, though underlying mechanisms are unclear. Prior studies have suggested that increased cumulative exposure to sex-steroid hormones and growth factors may impact both MD and MD-related breast cancer risk; however, most studies have only evaluated individual hormones. In this study, we simultaneously explored the relationship between 29 circulating hormones and growth factors with MD among postmenopausal women undergoing diagnostic breast biopsy. Methods We used data from 89 postmenopausal women, aged 44-65, who had complete measurements of 29 serum hormones from a single pre-biopsy blood draw (i.e., sex-steroid hormones: 15 estrogen/estrogen metabolites, 7 progesterone/progesterone metabolites; and non-sex hormones: insulin-like growth factor I and binding proteins (IGFBPs) 2-7). Volumetric MD (% fibroglandular volume) was assessed in pre-biopsy digital mammograms using single X-ray absorptiometry. Sufficient dimension reduction methods were used to compute a composite marker score that accommodates correlations among hormones and their relationship to MD. Backward elimination was applied to select log-transformed hormones contributing to the score at α=0.05; multivariable linear regression was used to further examine associations between selected hormones and MD within a single model, adjusting for age and BMI. Results Pearson correlations between hormones were moderate-to-strong. Dimension reduction methods identified 6 hormones as associated with MD (p&lt;0.05): estradiol, 2-hydroxyestradiol, 2-methoxyestrone, 16-ketoestradiol, IGFBP-2, and 17α-hydroxyprogesterone, in models that considered MD as either continuous or dichotomous (&gt;median vs. ≤median); BMI was consistently identified as the most significant predictor of MD (P &lt;0.0001). In a multivariable linear regression model that included these 6 hormones, in addition to age and BMI, higher levels of 2-methoxyestrone, IGFBP-2, and 17α-hydroxyprogesterone were significantly associated with increased MD, whereas higher levels of age and BMI were significantly associated with lower MD. Conclusions We identified 6 out of 29 correlated hormones that were significantly associated with MD among postmenopausal women. For several, the directions of their associations with MD were comparable to those observed in prior studies that have separately evaluated these hormones in relation to breast cancer risk. We plan to further explore how circulating hormones concurrently affect MD in premenopausal women, accounting for menstrual cycle phase. Incorporation of dimension reduction methods in studies of multiple correlated hormones can help uncover new etiologic insights into the role of hormones and growth factors in MD and breast carcinogenesis and inform strategies for prevention. Citation Format: Shaoqi Fan, Ruth M. Pfeiffer, Manila Hada, Roni T. Falk, Maeve Mullooly, Hannah Oh, Berta Geller, Pamela Vacek, Donald Weave, John Shepherd, Jeff Wang, Sally Herschorn, Louise A. Brinton, Xia Xu, Mark E. Sherman, Britton Trabert, Gretchen L. Gierach. Associations of circulating hormones with mammographic density in postmenopausal women referred to diagnostic breast biopsy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3488.