Characteristics and Outcomes of Patients With Pregnancy-Related End-Stage Kidney Disease.

Importance: The incidence of pregnancy-related acute kidney injury is increasing and is associated with significant maternal morbidity including progression to end-stage kidney disease (ESKD). Little is known about characteristics and long-term outcomes of patients who develop pregnancy-related ESKD. Objectives: To examine the characteristics and clinical outcomes of patients with pregnancy-related ESKD and to investigate associations between pre-ESKD nephrology care and outcomes. Design, Setting, and Participants: This was a cohort study of 183 640 reproductive-aged women with incident ESKD between January 1, 2000, and November 20, 2020, from the US Renal Data System and maternal data from births captured in the US Centers for Disease Control and Prevention publicly available natality data. Data were analyzed from December 2022 to June 2023. Exposure: Pregnancy-related primary cause of ESKD, per International Classification of Diseases, Ninth Revision (ICD-9) and ICD-10 codes reported at ESKD onset by the primary nephrologist on Centers for Medicare and Medicaid Services form 2728. Main Outcomes Measures: Multivariable Cox proportional hazards and competing risk models were constructed to examine time to (1) mortality, (2) access to kidney transplant (joining the waiting list or receiving a live donor transplant), and (3) receipt of transplant after joining the waitlist. Results: A total of 341 patients with a pregnancy-related primary cause of ESKD were identified (mean [SD] age 30.2 [7.3]). Compared with the general US birthing population, Black patients were overrepresented among those with pregnancy-related ESKD (109 patients [31.9%] vs 585 268 patients [16.2%]). In adjusted analyses, patients with pregnancy-related ESKD had similar or lower hazards of mortality compared with those with glomerulonephritis or cystic kidney disease (adjusted hazard ratio [aHR], 0.96; 95% CI, 0.76-1.19), diabetes or hypertension (aHR, 0.49; 95% CI, 0.39-0.61), or other or unknown primary causes of ESKD (aHR, 0.60; 95% CI, 0.48-0.75). Despite this, patients with pregnancy-related ESKD had significantly lower access to kidney transplant compared with those with other causes of ESKD, including (1) glomerulonephritis or cystic kidney disease (adjusted subhazard ratio [aSHR], 0.51; 95% CI, 0.43-0.66), (2) diabetes or hypertension (aSHR, 0.81; 95% CI, 0.67-0.98), and (3) other or unkown cause (aSHR, 0.82; 95% CI, 0.67-0.99). Those with pregnancy-related ESKD were less likely to have nephrology care or have a graft or arteriovenous fistula placed before ESKD onset (nephrology care: adjusted relative risk [aRR], 0.47; 95% CI, 0.40-0.56; graft or arteriovenous fistula placed: aRR, 0.31; 95% CI, 0.17-0.57). Conclusion and Relevance: In this study, those with pregnancy-related ESKD had reduced access to transplant and nephrology care, which could exacerbate existing disparities in a disproportionately Black population. Increased access to care could improve quality of life and health outcomes among these young adults with high potential for long-term survival.

Sex Hormones and Diabetes in 45- to 74-year-old Men and Postmenopausal Women: The Hispanic Community Health Study.

Previous studies demonstrated associations of endogenous sex hormones with diabetes. Less is known about their dynamic relationship with diabetes progression through different stages of the disease, independence of associations, and role of the hypothalamic-pituitary gonadal axis. The purpose of this analysis was to examine relationships of endogenous sex hormones with incident diabetes, prediabetes, and diabetes traits in 693 postmenopausal women and 1015 men aged 45 to 74 years without diabetes at baseline participating in the Hispanic Community Health Study/Study of Latinos and followed for 6 years. Baseline hormones included estradiol, luteinizing hormone (LH), follicle stimulating hormone (FSH), sex hormone-binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEAS), and, in men, testosterone and bioavailable testosterone. Associations were analyzed using multivariable Poisson and linear regressions. In men, testosterone was inversely associated with conversion from prediabetes to diabetes (incidence rate ratio [IRR] for 1 SD increase in testosterone: 0.821; 95% CI, 0.676, 0.997; P = 0.046), but not conversion from normoglycemia to prediabetes. Estradiol was positively associated with increase in fasting insulin and homeostatic model assessment of insulin resistance. In women, SHBG was inversely associated with change in glycosylated hemoglobin, postload glucose, and conversion from prediabetes to diabetes (IRR = 0.62; 95% CI, 0.44, 0.86, P = 0.005) but not from normoglycemia to prediabetes. Relationships with other hormones varied across glycemic measures. Stronger associations of testosterone and SHBG with transition from prediabetes to diabetes than from normoglycemic to prediabetes suggest they are operative at later stages of diabetes development. Biologic pathways by which sex hormones affect glucose homeostasis await future studies.

Association Between Estimated Pulse Wave Velocity and Cognitive Performance in Older Black and White Adults in NHANES.

BACKGROUND: Aging-associated cognitive decline is greater in non-Hispanic Black (NHB) adults than non-Hispanic White (NHW) adults. An important risk factor for cognitive decline with aging is arterial stiffening, though the importance to racial variation remains poorly understood. OBJECTIVE: We examined the association of an estimate of arterial stiffness with cognitive function in a bi-racial sample of 60-85-year-old adults (N = 3,616, 26.5% NHB) enrolled in the National Health and Nutrition Examination Survey (NHANES) between 1999-2002 and 2011-2014. METHODS: As a measure of vascular aging, pulse wave velocity was estimated (ePWV) using an equation incorporating age and mean arterial pressure and expressed as m/s. Using the digit symbol substitution test (DSST), cognitive function was expressed as the number of correctly matched symbols (out of 133) within 120 s. Linear regression models examined associations between ePWV and DSST. RESULTS: In models that adjusted for sex, education, smoking, body mass index, history of cardiovascular disease, and hypertension, ePWV was inversely associated with DSST score in NHB adults (ß= -3.47, 95% CI = -3.9 to -3.0; p < 0.001) and NHW adults (ß= -3.51, 95% CI = -4.4 to -2.6; p < 0.001). CONCLUSION: ePWV is inversely associated with a measure of cognitive function in older Black and White adults. ePWV may be a useful measure of vascular aging that can offer insight into cognitive aging.

Arterial stiffness and contralateral differences in blood pressure: The Atherosclerosis Risk in Communities (ARIC) study.

A large interarm difference in brachial systolic blood pressure (SBP) (≥10 or ≥15 mmHg) is strongly associated with elevated cardiovascular events and mortality. Evidence demonstrating whether such contralateral differences in SBP occur in ankle blood pressure and its association with arterial stiffness is scarce. The aims of this study were to characterize arm and ankle contralateral SBP differences in a sample of community-dwelling older adults (5077), and to determine whether this difference is associated with arterial stiffness assessed by pulse wave velocity (PWV) between the heart and ankle (haPWV), femoral artery and ankle (faPWV), and brachial artery and ankle (baPWV) in the right and left sides. Prevalence of interarm SBP differences ≥10 and ≥15 mmHg was 5.1% and .7%, respectively; the corresponding prevalence for interankle SBP was 24.9% and 12.0%. Higher BMI and lower ankle-brachial index (ABI) were significantly correlated with greater interarm SBP differences. Increased age, higher BMI, lower ABI, and greater contralateral differences in haPWV, faPWV, and baPWV were significantly correlated to greater interankle SBP differences. Interankle SBP difference ≥15 mmHg was significantly associated with contralateral differences of >80 cm/s in haPWV (OR = 1.94 [95% CI = 1.52-2.49]), >165 cm/s in faPWV (OR = 1.64 [95% CI = 1.27-2.12]), and >240 cm/s in baPWV (OR = 2.43 [95% CI = 1.94-3.05]). The associations remained significant after adjustment for age, sex, race, BMI, smoking status, and ABI. Compared with interarm differences, interankle differences in SBP are common in older adults. The magnitude of interankle, but not interarm, differences in SBP is associated with various measures of arterial stiffness.

Associations between estimated and measured carotid-femoral pulse wave velocity in older Black and White adults: the atherosclerosis risk in communities (ARIC) study.

Introduction: Aortic stiffness offers important insight into vascular aging and cardiovascular disease (CVD) risk. The referent measure of aortic stiffness is carotid-femoral pulse wave velocity (cfPWV). cfPWV can be estimated (ePWV) from age and mean arterial pressure. Few studies have directly compared the association of ePWV to measured cfPWV, particularly in non-White adults. Moreover, whether ePWV and cfPWV correlate similarly with CVD risk remains unexplored. Aim: (1) To estimate the strength of the agreement between ePWV and cfPWV in both Black and White older adults; and (2) to compare the associations of ePWV and cfPWV with CVD risk factors and determine whether these associations were consistent across races. Methods and Results: We evaluated 4478 [75.2 (SD 5.0) years] Black and White older adults in the Atherosclerosis Risk in Communities (ARIC) Study. cfPWV was measured using an automated pulse waveform analyzer. ePWV was derived from an equation based on age and mean arterial pressure. Association and agreement between the two measurements were determined using Pearson's correlation coefficient (r), standard error of estimate (SEE), and Bland-Altman analysis. Associations between traditional risk factors with ePWV and cfPWV were evaluated using linear mixed regression models. We observed weak correlations between ePWV and cfPWV within White adults (r = 0.36) and Black adults (r = 0.31). The mean bias for Bland-Altman analysis was low at -0.17 m/s (95%CI: -0.25 to -0.09). However, the inspection of the Bland-Altman plots indicated systematic bias (P < 0.001), which was consistent across race strata. The SEE, or typical absolute error, was 2.8 m/s suggesting high variability across measures. In models adjusted for sex, prevalent diabetes, the number of prevalent cardiovascular diseases, and medication count, both cfPWV and ePWV were positively associated with heart rate, triglycerides, and fasting glucose, and negatively associated with body mass index (BMI) and smoking status in White adults (P < 0.05). cfPWV and ePWV were not associated with heart rate, triglycerides, and fasting glucose in Black adults, while both measures were negatively associated with BMI in Black adults. Conclusions: Findings suggest a weak association between ePWV and cfPWV in older White and Black adults from ARIC. There were similar weak associations between CVD risk factors with ePWV and cfPWV in White adults with subtle differences in associations in Black adults.

Associations of lower-limb atherosclerosis and arteriosclerosis with cardiovascular risk factors and disease in older adults: The Atherosclerosis Risk in Communities (ARIC) study.

BACKGROUND & AIMS: Atherosclerosis and arteriosclerosis contribute to vascular aging and cardiovascular disease (CVD) risk. Both processes can be assessed simply in the lower-limbs and reflect systemic pathology. However, only atherosclerosis is routinely assessed, typically via ankle-brachial index (ABI). Arteriosclerosis can be assessed using femoral-ankle pulse wave velocity (faPWV), but no studies have identified whether ABI and faPWV similarly associate with overt CVD and risk factors, nor whether faPWV confers additional information. The aims of this study were to (i) compare associations of ABI and faPWV with traditional CVD risk factors, including age, sex, systolic blood pressure (SBP), high-density lipoprotein (HDL), total cholesterol (TC), smoking, and diabetes; and (ii) determine the independent and additive associations of ABI and faPWV with a composite measure of prevalent CVD. METHODS: We evaluated ABI and faPWV in 4330 older-aged (75.3 ± 5.0 years) adults using an oscillometric screening device. Associations between ABI and faPWV with CVD risk factors and CVD were determined using mixed-model linear- and logistic-regression. RESULTS: ABI and faPWV were associated with age, HDL, and smoking. ABI was associated with sex, TC, diabetes. faPWV was associated with SBP. Both ABI and faPWV were inversely associated with CVD. Low ABI (≤0.9 vs. >0.9) and low faPWV (≤9.94 vs. >9.94) increased the odds of CVD by 2.41-fold (95% CI:1.85,3.17) and 1.46-fold (95% CI:1.23,1.74), respectively. The inverse association between faPWV and CVD was independent of ABI and CVD risk factors. CONCLUSIONS: ABI and faPWV, measures of lower-limb atherosclerosis and arteriosclerosis, are independently associated with CVD risk factors and prevalent CVD. Assessment of faPWV may confer additional risk information beyond ABI.

Polycystic Ovary Syndrome Signs and Metabolic Syndrome in Premenopausal Hispanic/Latina Women: the HCHS/SOL Study.

CONTEXT: Polycystic ovary syndrome (PCOS), a condition of androgen excess in women, is associated with cardiometabolic risk factors; however, this association is not fully characterized in a population-based sample of premenopausal women and high-risk groups such as Hispanics/Latinas. OBJECTIVE: We examined the association of PCOS signs and metabolic syndrome (MetS) in premenopausal Hispanic/Latina women. METHODS: This cross-sectional analysis includes 1427 women age 24 to 44 years from the Hispanic Community Health Study/Study of Latinos. PCOS signs included menstrual cycle greater than 35 days or irregular, self-reported PCOS, and oral contraceptive use to regulate periods or acne, and a composite of 1 or more PCOS signs. We calculated odds ratios (OR) and 95% CI for MetS, accounting for sociodemographic factors and the complex survey design; an additional model included body mass index (BMI). RESULTS: The mean age was 34 years and 30% reported any PCOS sign. The odds of MetS were higher in women reporting cycles greater than 35 days or irregular (OR 1.63; CI: 1.07-2.49) vs cycles 24 to 35 days, self-reported PCOS (OR 2.49; CI: 1.38-4.50) vs no PCOS, and any PCOS sign (OR 1.58; CI: 1.10-2.26) vs none. We found no association between OC use to regulate periods or acne and MetS (OR 1.1; CI: 0.6-1.8). When adjusting for BMI, only the association of self-reported PCOS and MetS was attenuated (OR 1.78; CI: 0.92-3.44). CONCLUSIONS: In Hispanic/Latina women, irregular menstrual cycles, self-reported PCOS, and any PCOS sign were associated with MetS and could indicate women at metabolic disease risk.

Central arterial stiffness and retinal vessel calibers: the Atherosclerosis Risk in Communities Study-Neurocognitive Study.

BACKGROUND: The retinal microvasculature provides a window to the cerebral vasculature and enables examination of changes in retinal caliber that may mimic those occurring in cerebrovascular disease. The association of central arterial stiffness and retinal vessel caliber in a population sample is not fully understood. METHODS: In 1706 older adults (mean age 76.3, 58.1% women) from the population-based Atherosclerosis Risk in Communities Study, we examined the cross-sectional association of central arterial stiffness [carotid-femoral pulse wave velocity (cfPWV)] with retinal vessel calibers [central retinal arteriolar equivalent (CRAE) and central retinal vein equivalent (CRVE)]. We estimated the association of cfPWV with CRAE narrowing (<25th percentile) and CRVE widening (>75th percentile) after adjustment for age, sex, race-field center, BMI, smoking, and type 2 diabetes. We tested for effect modification by sex, hypertension, and type 2 diabetes. RESULTS: Carotid-femoral PWV (m/s) was not associated with the odds of CRAE narrowing [odds ratio (OR): 0.99; 95% CI: 0.95-1.03]. The association of cfPWV with CRVE widening was stronger in those without hypertension (OR: 1.10; 95% CI: 1.01-1.20) versus those with hypertension (OR: 1.01 95% CI: 0.96-1.05) and slightly stronger in those with type 2 diabetes (OR: 1.07; 95% CI: 1.00-1.14) versus without type 2 diabetes (OR: 1.01; 95% CI: 0.96-1.06). CONCLUSIONS: In older adults, cfPWV was associated with wider retinal venular caliber, particularly in individuals without hypertension. Central arterial stiffening may be associated with cerebral microvascular changes, as exhibited in its retinal vasculature component.

The association of age at menopause and all-cause and cause-specific mortality by race, postmenopausal hormone use, and smoking status.

While a mean age at menopause of 51 years has been reported in the United States (U.S.), some U.S. women experience menopause before age 45, possibly increasing risk of cardiovascular mortality; however, the role in all-cause and cerebrovascular-related mortality is unclear. The purpose of this study was to investigate the association between age at menopause and all-cause and cause-specific mortality by race, hormone replacement therapy (HRT) use, and smoking status. REasons for Geographic and Racial Differences in Stroke (REGARDS) is a population-based study of 30,239 participants aged ≥45 years enrolled between 2003 and 2007 of whom 14,361 were postmenopausal women. Age at menopause was defined as <45 (early) or ≥45. All-cause and cause-specific mortality were ascertained through 2013. Cox proportional hazards models estimated hazard ratios (HR) and 95% confidence intervals (CI) for the association between age at menopause and mortality, adjusting for baseline measures. Of 11,287 eligible women (6403 white; 4884 black), mean menopause age was 45.2 (SD 7.9) with 1524 deaths over 7.1 years. Significant interactions were detected between early age at menopause (39%) and HRT use in association with all-cause mortality (p < 0.01), mortality from coronary heart disease (p = 0.06), and mortality from all other causes (p = 0.04). An association between early age at menopause and all-cause mortality was observed among ever-HRT users (HR = 1.31, 95% CI: 1.10-1.56), but not never-HRT users (HR = 1.01, 95% CI: 0.85-1.20). There were no differences in associations examined by race or smoking status. Increased all-cause mortality risk was observed for ever-HRT users with menopause before age 45.

Smoking Behaviors and Arterial Stiffness Measured by Pulse Wave Velocity in Older Adults: The Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Though smoking is strongly associated with peripheral vascular disease and arteriosclerosis, smoking's association with arterial stiffness has been inconsistent and mostly limited to a single arterial segment. We examined the relationship between smoking behaviors with arterial stiffness in multiple arterial segments among community dwelling older adults. METHODS: The cross-sectional relationship between smoking behavior with carotid-femoral (cfPWV) and femoral-ankle pulse wave velocity (faPWV) was examined in 5,002 men and women, separately, of the Atherosclerosis Risk in Communities (ARIC) cohort study. Brachial-ankle PWV was also assessed and presented in Supplementary Material. Heckman selection models were used to control for selective attrition and death in the ARIC cohort. RESULTS: In women, faPWV was lower in current smokers compared to never smokers (-66.0cm/s; 95% confidence interval (95% CI): -94.6, -37.4), and was 1.0cm/s lower (95% CI: -1.8, -0.2) for every additional year a woman smoked, after adjustment for confounders. Among women, cfPWV was not associated with smoking status or cigarette pack-years. Additionally, no associations of smoking status and cigarette pack-years with PWV were observed among men. Years since smoking cessation was not associated with PWV in either gender. CONCLUSION: Both smoking status and cumulative smoking exposure were associated with lower peripheral arterial stiffness among women, but not among men. We did not observe an association between central arterial stiffness and smoking status in either gender. The profound and well-documented adverse effects of cigarette smoking on the vasculature may not include a sustained stiffening of the arteries measured at older age.

Varying patterns of brachial artery flow-mediated dilatation in women with polycystic ovary syndrome and controls: An application of the group-based trajectory modeling.

PURPOSE: To identify changing patterns of absolute change in brachial artery lumen diameter (LD) after reactive hyperemia in women with polycystic ovary syndrome (PCOS) and controls and to quantify the association of PCOS status and participants' factors with these patterns. METHODS: Brachial flow-mediated dilation was measured in 128 women with PCOS and 148 controls aged 30-60 years. Group-based trajectory modeling was used to investigate absolute change in LD every 30 seconds for 2 minutes after occluding cuff deflation. Multinomial logistic regression was used to identify factors associated with trajectories. RESULTS: Three patterns emerged, namely nondilators (42.2%), dilators (44.6%), and enhanced dilators (13.0%). The proportion of women with PCOS did not differ across groups. Independently of age and PCOS status, larger baseline LD (odds ratio; 95% confidence interval: 2.51; 1.29, 4.89) and lower insulin levels (0.70; 0.52, 0.93) were associated with nondilators rather than with dilators. Higher total cholesterol was associated with dilators in women with PCOS but with nondilators in controls. CONCLUSIONS: Trajectory modeling identified distinct patterns of change in LD and factors associated with the endothelial response. This method may be a useful tool to understand the brachial flow-mediated vasodilator response.

Effects of an intensive behavioral weight loss intervention consisting of caloric restriction with or without physical activity on common carotid artery remodeling in severely obese adults.

OBJECTIVE: Obesity increases cardiovascular disease risk and adversely affects vascular structure and function. Few studies have evaluated the vascular effects of non-surgical weight reduction in the severely obese. We hypothesized that weight loss and improvements in cardiometabolic factors would reduce common carotid artery intima-media thickness (CIMT) and inter-adventitial diameter (AD) in severely obese adults. METHODS: We performed carotid ultrasound and measured cardiometabolic factors in 90 severely obese participants (body mass index (BMI)≥35 kg/m(2), age 30-55) at baseline and 6 months in a randomized clinical trial of dietary intervention with (n=45) or without (n=45) physical activity. RESULTS: The achieved weight loss (mean=8%) did not differ significantly by intervention group (P=0.10) and resulted in a 0.07 mm mean decrease in AD (P=0.001). AD change was positively correlated with changes in BMI, waist circumference, abdominal visceral and subcutaneous fat, and body fat mass, and AD decreased more in men (P<0.05 for all). After multivariable adjustment, changes in BMI (P=0.03) and abdominal subcutaneous fat (P=0.04) were significant determinants of AD change. Although CIMT did not decrease significantly overall (-0.008 mm, P=0.16), individuals who lost at least 5% of their body weight experienced a significant mean reduction in CIMT of 0.02 mm (P=0.002). CIMT change was positively correlated with changes in BMI, waist circumference, fat-free mass, leptin, and insulin (P<0.05 for all). After multivariable adjustment, insulin reduction remained a significant determinant of CIMT decrease (P=0.03). CONCLUSION: A 6 month intensive behavioral intervention can significantly reverse metabolic and vascular abnormalities in severely obese adults.

Carotid artery intima-media thickness in polycystic ovary syndrome: a systematic review and meta-analysis.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder associated with cardiovascular disease (CVD) risk factors and metabolic disturbances. This systematic review and meta-analysis was conducted to determine whether carotid intima-media thickness (CIMT), a marker of subclinical atherosclerosis, is higher in women with PCOS compared with women without PCOS. METHODS: Primary articles reporting the mean CIMT in women with PCOS and controls were identified using Ovid MEDLINE, EMBASE and PUBMED. We performed a random-effects meta-analysis and created forest plots of the mean difference in CIMT and conducted tests for heterogeneity and publication bias. Studies were grouped by quality, defined by reporting reproducibility of CIMT and averaging both common carotid arteries versus one side for CIMT. RESULTS: From the 36 eligible full-text studies, 8 studies were included in the systematic review and 19 studies were included in the meta-analysis (total n= 1123 women with PCOS, n= 923 controls). The summary mean difference in CIMT among women with PCOS compared with controls was 0.072 mm [95% confidence interval (CI) 0.040, 0.105, P < 0.0001] for highest quality studies, 0.084 mm (95% CI 0.042, 0.126, P = 0.0001) for good quality studies, 0.041 (95% CI -0.038, 0.120, P = 0.310) for fair-quality studies and 0.045 (95% CI -0.020, 0.111, P = 0.173) for lower quality studies. CONCLUSIONS: Larger studies with a well-defined PCOS population using rigorous methodology may be required to draw a more robust conclusion. However, these results suggest women with PCOS are at a greater risk of premature atherosclerosis, which emphasizes the importance of screening and monitoring CVD risk factors in women with PCOS.

Conservation of cytoplasmic organization in the cystidia of Suillus species.

Cystidia of Suillus americanus and S. granulatus (Boletales) were examined cytochemically and ultrastructurally with cells prepared by freeze substitution. We present the first study showing ultrastructural details and cytological functions of the cystidium to be conserved in two closely related species. The results are presented for inclusion in the AFTOL Structural and Biochemical Database to aid in the application of morphological characters to phylogenetic studies. The cystidia of these Suillus species appear to be united by a series of conserved characters, including specialized secretion mechanisms, smooth tubular endoplasmic reticulum and abundant free ribosomes. The conservation of these subcellular traits among members of this genus suggests that ultrastructural details of cystidia may provide a suite of phylogenetically informative characters. Inclusion of such characters in phylogenetic analyses might resolve or provide support for monophyletic groups at the level of family or genus.