About

Carrie A. Karvonen-Gutierrez, PhD, MPH, is an Associate Professor in the Department of Epidemiology and the Associate Chair for Faculty Affairs at the University of Michigan School of Public Health. She is also the Director of the Center for Lifecourse Epidemiology and Aging Research. Her scholarly focus is on the impact of reproductive aging, chronological aging, and obesity on age-related health outcomes, including physical functioning, frailty, osteoarthritis, disability, and cardiometabolic dysfunction. Dr. Karvonen-Gutierrez leads a research portfolio that includes NIH-funded studies such as the Study of Women’s Health Across the Nation (SWAN)-Aging and the Michigan Bone Health and Metabolism Study, both of which include extensive longitudinal data on women from midlife through early old age. Her expertise encompasses the biology and pathophysiology of common etiologic factors underlying chronic diseases, such as inflammation and metabolic dysfunction, with a focus on analyzing and interpreting longitudinal data related to aging and inflammation as metabolic risk factors. She holds a PhD in Epidemiologic Science and an MPH in Epidemiology from the University of Michigan, and a BA in Biology from the University of Northern Iowa. Her research aims to understand how critical life stages and transitions influence metabolic and musculoskeletal health outcomes, with specific aims including identifying biomarkers related to osteoarthritis, describing risk factors for physical function limitations, characterizing changes in bone health across menopause, and identifying environmental exposures associated with metabolic dysfunction in women.

Selected publications

• Longitudinal Associations of Perfluoroalkyl and Polyfluoroalkyl Substances with Inflammatory and Hemostatic Biomarkers: The Study of Women’s Health Across the Nation

  ISEE Conference Abstracts · 2024-07-31

  articleOpen access
  PublisherDOI

• Perfluoroalkyl and polyfluoroalkyl substances (PFAS) and PFAS Mixtures with Incident Hypertension: the Study of Women’s Health Across the Nation 1999-2017

  ISEE Conference Abstracts · 2021-08-23

  articleOpen access

  BACKGROUND AND AIM: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure may cause a variety of hypertension-inducing pathophysiological responses. However, the one epidemiologic study that has examined PFAS and hypertension incidence in adults reported no significant associations. This study aimed to examine the associations between PFAS and incident hypertension. METHODS: This study included 1,058 midlife women free of hypertension from the multi-racial/ethnic Study of Women’s Health Across the Nation (SWAN) Multi-Pollutant Study with approximately annual follow-up visits between 1999 and 2017. Baseline serum PFAS concentrations were quantified by high-performance liquid chromatography-isotope dilution-tandem mass spectrometry. Hypertension was defined as blood pressure ≥140 mmHg systolic or ≥90 mmHg diastolic or receiving anti-hypertensive treatment. Cox proportional hazards (PH) model were utilized to calculate hazards ratios (HR) and 95% confidence intervals (CI) with adjustment for race/ethnicity, study site, educational attainment, financial strain, smoking status, passive smoking, alcohol consumption, total calorie intake, menopausal status, and body mass index. Elastic net-penalized Cox PH regression was implemented to model PFAS mixtures and construct an integrative index, environmental risk score (ERS), to evaluate the joint effect of PFAS mixtures. RESULTS:During 11,843 person-years of follow-up, 470 participants developed incident hypertension. Compared with the lowest tertile, women in the highest tertile of baseline serum concentrations had adjusted HRs of 1.36 (95% CI: 1.08-1.73) for total perfluorooctane sulfonate (PFOS) (P-trend=0.01), 1.31 (95% CI: 1.03-1.67) for linear perfluorooctanoate (n-PFOA) (P-trend=0.01), and 1.37 (95% CI: 1.07-1.75) for 2-(N-ethyl-perfluorooctane sulfonamido) acetate (EtFOSAA) (P-trend=0.01). No significant associations were observed for perfluorononanoate (PFNA) and perfluorohexane sulfonate (PFHxS). In the mixture analysis, women in the highest tertile of ERS had an HR of 1.53 (95% CI: 1.20-1.96) (P-trend=0.0008), compared with those in the lowest tertile. CONCLUSIONS:Our findings suggest an association between PFAS and incident hypertension. PFAS may be an underappreciated contributing factor to women’s cardiovascular disease risk. KEYWORDS: PFAS, Mixtures, Mixture analysis, Cardiovascular diseases

  PublisherDOI

• Perfluoroalkyl and Polyfluoroalkyl Substances and Body Size and Composition Trajectories: the Study of Women’s Health Across the Nation 1999-2018

  ISEE Conference Abstracts · 2021-08-23

  articleOpen access

  BACKGROUND AND AIM: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been suggested as obesogens but epidemiologic evidence is limited. We examined associations of serum PFAS concentrations with longitudinal trajectories of weight, waist circumference (WC), fat mass and proportion fat in midlife women. METHODS: This study included 1,381 midlife women, with a total of 15,000 repeated measures from the multi-racial/ethnic Study of Women’s Health Across the Nation between 1999 and 2018. The average follow-up was 14.9 (range: 0-18.6) years. Body size (objectively measured weight and WC) and body composition from dual-energy X-ray absorptiometry were assessed at near-annual visits. Linear mixed models with piecewise linear splines were utilized to model non-linear trajectories of body size and composition. RESULTS:After multivariable adjustment, PFAS concentrations were positively associated with weight, WC, fat mass, and proportion fat at baseline and during follow-up. Comparing the highest to the lowest tertiles of PFAS concentrations, adjusted geometric mean weight was 73.9 kg vs. 69.6 kg for PFOS (P0.0001), and 74.0 vs. 69.4 kg for linear PFOA (P0.0001) at baseline. Women with the highest tertile of PFOS had an annual increase rate of 0.33% (95% CI: 0.27%, 0.40%) in weight, compared to the lowest tertile with 0.10% (95% CI: 0.04%, 0.17%) (P0.0001). PFOS was also significantly related to higher increase rates in WC (difference=0.12% per year, P=0.002) and fat mass (difference=0.25% per year, P=0.0002). EtFOSAA and MeFOSAA showed similar effects to PFOS. Although PFHxS was not related to body size or fat at baseline, PFHxS was significantly associated with accelerated increases in weight (P0.0001), WC (P=0.003), fat mass (P0.0001), and proportion fat (P=0.0009). No significant results were found for PFNA. CONCLUSIONS:Certain PFAS were positively associated with large body size and body fat, and higher increase rates over time. PFAS may be an underappreciated contributing factor to obesity risk. KEYWORDS: PFAS, Obesity and metabolic disorders

  PublisherDOI

• Urinary Metal Mixtures and Incident Metabolic Syndrome in Midlife Women: the Study of Women’s Health Across the Nation (SWAN)

  ISEE Conference Abstracts · 2021-08-23

  articleOpen access

  BACKGROUND AND AIM: Exposure to metals may contribute to the development of metabolic syndrome (MetS); however, evidence from midlife women who are at greater risk of cardiometabolic disease is limited. We prospectively examined the associations of 15 urinary metal concentrations with incident MetS in the Study of Women’s Health Across the Nation Multi-Pollutant Study. METHODS: The sample included 947 White, Black, Chinese and Japanese women from 5 study sites in the United States, aged 45-56 years and free of MetS at baseline (1999-2000), followed through 2017. Urinary concentrations of 15 metals, including arsenic, barium, cadmium, cobalt, cesium, copper, mercury, manganese, molybdenum, nickel, lead, antimony, tin, thallium, and zinc, were quantified at baseline. Incident MetS was identified annually as the presence of at least 3 of the following 5 components: high blood pressure, impaired fasting glucose, abdominal obesity, high triglycerides, and low high-density lipoprotein cholesterol. RESULTS:After adjustment for potential confounders, the hazard ratios (HR) (95% confidence interval (CI)) for MetS associated with each doubling of urinary metal concentration was 1.14 (1.08, 1.23) for arsenic, 1.14 (1.01, 1.29) for cobalt, and 1.20 (1.06, 1.37) for zinc, in Cox proportional hazards models. Positive associations of urinary arsenic with high blood pressure and impaired fasting glucose, positive associations of urinary cobalt with high blood pressure and abdominal obesity, and positive associations of urinary zinc with high blood pressure, impaired fasting glucose, abdominal obesity, and high triglyceride were observed. In the quantile-based g-computation assessing the joint effect of metal mixtures, increasing urinary arsenic, cobalt, and zinc concentrations by one quartile was associated with a higher incidence of MetS (HR=1.73, 95% CI: 1.21, 2.48). CONCLUSIONS:Higher urinary arsenic, cobalt, and zinc concentrations were associated with an elevated incidence of MetS in midlife women. Future studies should confirm these findings and further investigate the underlying mechanisms. KEYWORDS: Metals, mixtures, metabolic syndrome, women, cohort study.

  PublisherDOI

• Exposure to Phthalates May Accelerate Body Fat Gain in Midlife Women: The Study of Women’s Health Across the Nation (SWAN)

  ISEE Conference Abstracts · 2021-08-23

  articleOpen access

  BACKGROUND AND AIM: Phthalates may disrupt energy balance in animals, but their effects in humans remain uncertain. We examined whether phthalate exposure was associated with body fat gain in midlife women. METHODS: We analyzed longitudinal data from 1369 women in the Study of Women’s Health Across the Nation Multi-Pollutant Study. Eleven phthalate metabolites measured in spot urine samples at baseline (1999/2000) were standardized with covariate-adjusted creatinine. Body weight (BW), percent body fat (BF%), and waist-to-hip ratio (WHR) were measured near-annually until 2016/2017. For each metabolite, linear mixed effects models with interaction terms between time and log₂(metabolite) were used to predict outcomes, adjusting for demographic, lifestyle, and menopause-related factors. Analyses were conducted overall and stratified by baseline obesity status due to heterogeneity in outcome trajectories. All analyses were repeated using a second set of metabolites measured in 2002/2003 to evaluate findings’ robustness. RESULTS:In all women, metabolites of di(2-ethylhexyl) phthalate (DEHP), monobenzyl phthalate (MBzP), mono-carboxyoctyl phthalate (MCOP), and mono(3-carboxypropyl) phthalate (MCPP) were associated with faster increases in BF%. The difference in the rate of change per doubling of metabolites ranged from 0.012 percentage point (pp)/year (95% confidence interval (CI): 0.00014, 0.023) for MBzP to 0.019 pp/year (95% CI: 0.0044, 0.033) for MCPP. Stratified analyses revealed that positive associations occurred primarily in women who were normal/underweight at baseline, where mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), MBzP, and MCPP were associated with faster increases in all outcomes. For instance, each doubling of MnBP was associated with 0.091% (95% CI: 0.0025, 0.18), 0.029 pp/year (95% CI: 0.0083, 0.049), and 0.025% (95% CI: 0.0020, 0.047) faster increases in BW, BF%, and WHR, respectively. Most associations were attenuated and non-significant when using exposure data from 2002/2003. CONCLUSIONS:Some phthalate metabolites were associated with fat gains in midlife women, but results may be sensitive to the timing of exposure. KEYWORDS: Phthalates, Endocrine disrupting chemicals, Obesity and metabolic disorders, Female, Environmental epidemiology

  PublisherDOI

• Urinary Heavy Metals and Longitudinal Changes in Blood Pressure in Midlife Women: the Study of Women’s Health Across the Nation

  ISEE Conference Abstracts · 2021-08-23

  articleOpen access

  BACKGROUND AND AIM: Environmental exposure to heavy metals may contribute to increased blood pressure, however, evidence from midlife women who are at greater risk of cardio-metabolic disease, is limited. We evaluated the associations of urinary concentrations of arsenic, cadmium, mercury, and lead with longitudinal changes in blood pressure in the Study of Women’s Health Across the Nation Multi-Pollutant Study. METHODS: The sample included 1,317 White, Black, Chinese and Japanese women, aged 45-56 years at baseline (1999-2000), whose systolic and diastolic blood pressure (SBP and DBP) were measured annually or biannually through 2017. Urinary metal concentrations were determined at baseline. Longitudinal changes in SBP and DBP were modeled using linear mixed effects models by tertiles of metal concentrations. RESULTS:After multivariable adjustment, estimated annualized increases (95% CI) in SBP in the highest and lowest tertiles were 0.93 (0.85, 1.01) mmHg and 0.74 (0.66, 0.82) mmHg for arsenic, 0.82 (0.75, 0.90) mmHg and 0.72 (0.65, 0.80) mmHg for mercury, and 0.86 (0.78, 0.93) mmHg and 0.72 (0.64, 0.79) mmHg for lead, respectively. Similar results were observed for associations of arsenic, mercury, lead with DBP. Urinary cadmium was associated with a greater rate of increase in SBP only among never smokers. Women with higher concentrations of all four metals had greater annualized increases in SBP and DBP than those with lower concentrations. CONCLUSIONS:Our findings suggest that exposure to heavy metals may accelerate the increase in blood pressure in midlife women, supporting the need for continued efforts to reduce these environmental exposures. KEYWORDS: Metals, blood pressure, women, cohort study

  PublisherDOI

• Associations of Perfluoroalkyl and Polyfluoroalkyl Substances (PFAS) and PFAS Mixtures with Adipokines in Midlife Women

  ISEE Conference Abstracts · 2021-08-23 · 2 citations

  articleOpen access

  BACKGROUND AND AIM: Perfluoroalkyl and polyfluoroalkyl substances (PFAS) exposure have been associated with obesity and related comorbidities. However, underlying mechanisms are not well understood. We determined if serum PFAS concentrations were associated with adipokine profiles in midlife women. METHODS: We examined 1,245 women aged 45-56 years from the Study of Women’s Health Across the Nation. Concentrations of 11 PFAS were quantified in baseline serum samples collected in 1999-2000. Linear and branched perfluorooctane sulfonic acid isomers (n-PFOS and Sm-PFOS) and their sum (PFOS), linear perfluorooctanoic acid (n-PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA), and 2-(N-ethyl-perfluorooctane sulfonamido) acetic acid (EtFOSAA) with detection frequencies 60% were included in the analysis. Adipokines including leptin, soluble leptin receptor (sOB-R), free leptin index (FLI, the ratio of leptin to sOB-R), total and high molecular weight (HMW) adiponectin were assessed in 2002-2003. We utilized multivariable linear regressions and Bayesian kernel machine regression (BKMR) to assess individual and overall joint effects of PFAS on adipokines with adjustment for age, race/ethnicity, study site, education, smoking status, physical activity, menopausal status, and waist circumference. RESULTS:A doubling of PFAS concentrations was associated with 7.8% (95% CI: 2.5%, 13.4%) higher FLI for PFOS, 9.4% (95% CI: 3.7%, 15.3%) for n-PFOA, 5.5% (95% CI: 2.2%, 9.0%) for EtFOSAA and 7.4% (95% CI: 2.8%, 12.2%) for MeFOSAA. Similar associations were found for leptin. Only EtFOSAA was associated with lower sOB-R concentrations (1.4% lower, 95% CI: -2.7%, -0.1%). In BKMR analysis, women with PFAS concentrations at the median and the 90th percentile had 30.9% (95% CI: 15.6%, 48.3%) and 52.1% (95% CI: 27.9%, 81.0%) higher FLI, respectively, compared with those with concentrations fixed at the 10th percentile. CONCLUSIONS:Some PFAS may alter circulating levels of leptin. Understanding associations between PFAS and adipokines may help elucidate whether PFAS can influence obesity and metabolic disease. KEYWORDS: PFAS, Mixtures, Mixture analysis, Obesity and metabolic disorders

  PublisherDOI

Labs

• Center for Lifecourse Epidemiology and Aging ResearchPI