Ovary as a Biomarker of Health and Longevity: Insights from Genetics

AbstractReproductive fitness and its influence on overall health has been a topic of significant study and interest. Multiple studies have found that age at last reproduction associates with overall health. Women who conceive later in life are significantly more likely to outlive their peers who are unable to conceive. The mechanisms behind these observations are not well understood. Earlier age at menopause associates with shorter life span, increased risk for diabetes mellitus, and increased risk of heart disease, and represents a surrogate marker for the age at last reproduction. Recent applications of genome-wide association studies as well as whole-exome sequencing to familial primary ovarian insufficiency (POI) and menopause have identified new genomic regions that link reproductive aging and adverse health outcomes. The preponderance of DNA damage response genes in menopause and POI represents a relatively new paradigm in this area, and links overall aging and reproduction at the molecular level. Identification of the subset of individuals who are at risk for adverse health outcomes remains a significant and high priority research challenge. The combination of epidemiologic studies in women with diminished ovarian reserves, ovarian insufficiency, and early menopause, as well as appropriate animal studies, will be necessary to dissect genotype–phenotype correlations not only in the cause of ovarian dysfunction but also in the cause of adverse health outcomes.

Download Full-text

Sarcopenia: a Muscle Disease with Decreased Functional Capacity and an Increased Risk of Adverse Health Outcomes

Current Physical Medicine and Rehabilitation Reports ◽

10.1007/s40141-019-00236-5 ◽

2019 ◽

Vol 7 (3) ◽

pp. 290-296 ◽

Cited By ~ 1

Author(s):

Daniel Rooks

Keyword(s):

Health Outcomes ◽

Functional Capacity ◽

Muscle Disease ◽

Adverse Health ◽

Adverse Health Outcomes ◽

Increased Risk

Download Full-text

Are Children Born After Assisted Reproductive Technology at Increased Risk for Adverse Health Outcomes?

Obstetrics and Gynecology ◽

10.1097/01.aog.0000124571.04890.67 ◽

2004 ◽

Vol 103 (6) ◽

pp. 1154-1163 ◽

Cited By ~ 95

Author(s):

Laura A. Schieve ◽

Sonja A. Rasmussen ◽

Germaine M. Buck ◽

Diana E. Schendel ◽

Meredith A. Reynolds ◽

...

Keyword(s):

Health Outcomes ◽

Assisted Reproductive Technology ◽

Reproductive Technology ◽

Adverse Health ◽

Adverse Health Outcomes ◽

Increased Risk

Download Full-text

Potentially inappropriate prescribing in dementia, multi-morbidity and incidence of adverse health outcomes

Age and Ageing ◽

10.1093/ageing/afaa147 ◽

2020 ◽

Author(s):

João Delgado ◽

Lindsay Jones ◽

Marie C Bradley ◽

Louise M Allan ◽

Clive Ballard ◽

...

Keyword(s):

Health Outcomes ◽

Inappropriate Prescribing ◽

Hazard Ratio ◽

Potentially Inappropriate Prescribing ◽

Prevalence Odds Ratio ◽

Discharge Data ◽

Adverse Health ◽

Adverse Health Outcomes ◽

Increased Risk ◽

The Impact

Abstract Importance treatment of dementia in individuals with comorbidities is complex, leading to potentially inappropriate prescribing (PIP). The impact of PIP in this population is unknown. Objective to estimate the rate of PIP and its effect on adverse health outcomes (AHO). Design retrospective cohort. Setting primary care electronic health records linked to hospital discharge data from England. Subjects 11,175 individuals with dementia aged over 65 years in 2016 and 43,463 age- and sex-matched controls. Methods Screening Tool of Older Persons’ Prescriptions V2 defined PIP. Logistic regression tested associations with comorbidities at baseline, and survival analyses risk of incident AHO, adjusted for age, gender, deprivation and 14 comorbidities. Results the dementia group had increased risk of PIP (73% prevalence; odds ratio [OR]: 1.92; confidence interval [CI]: 83–103%; P < 0.01) after adjusting for comorbidities. Most frequent PIP criteria were related to anti-cholinergic drugs and therapeutic duplication. Risk of PIP was higher in patients also diagnosed with coronary-heart disease (odds OR: 2.17; CI: 1.91–2.46; P < 0.01), severe mental illness (OR: 2.09; CI: 1.62–2.70; P < 0.01); and depression (OR: 1.81; CI: 1.62–2.01; P < 0.01). During follow-up (1 year), PIP was associated with increased all-cause mortality (hazard ratio: 1.14; CI: 1.02–1.26; P < 0.02), skin ulcer and pressure sores (hazard ratio: 1.66; CI: 1.12–2.46; P < 0.01), falls (hazard ratio: 1.37; CI: 1.15–1.63; P < 0.01), anaemia (hazard ratio: 1.61; CI: 1.10–2.38; P < 0.02) and osteoporosis (hazard ratio: 1.62; CI: 1.02–2.57; P < 0.04). Conclusion patients with dementia frequently receive PIPs, and those who do are more likely to experience AHO. These results highlight the need to optimise medication in dementia patients, especially those with comorbidities.

Download Full-text

Secondary hyperparathyroidism and adverse health outcomes in adults with chronic kidney disease

Clinical Kidney Journal ◽

10.1093/ckj/sfab006 ◽

2021 ◽

Author(s):

Yang Xu ◽

Marie Evans ◽

Marco Soro ◽

Peter Barany ◽

Juan Jesus Carrero

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Health Outcomes ◽

Secondary Hyperparathyroidism ◽

Ckd Progression ◽

Risk Of Death ◽

Adverse Health ◽

Adverse Health Outcomes ◽

Increased Risk ◽

Ckd Stage

Abstract Background Secondary hyperparathyroidism (sHPT) develops frequently in patients with chronic kidney disease (CKD). However, the burden and long-term impact of sHPT on the risk of adverse health outcomes are not well studied. Methods We evaluated all adults receiving nephrologist care in Stockholm during 2006–11 who were not undergoing kidney replacement therapy and had not developed sHPT. Incident sHPT was identified by using clinical diagnoses, initiated medications or two consecutive parathyroid hormone (PTH) measurements ≥130 pg/mL. We characterized sHPT incidence by estimated glomerular filtration rate (eGFR) strata, evaluated clinical predictors and quantified the association between incident sHPT (time-varying exposure) and the risk of fractures, CKD progression, major adverse cardiovascular events (MACEs) and death. Results We identified 2556 adults with CKD Stages 1–5 (mean age 66 years, 38% women), of whom 784 developed sHPT during follow-up. The incidence of sHPT increased with advancing CKD: from 57 cases/1000 person-years in CKD Stage G3 to 230 cases/1000 person-years in Stage G5. In multivariable analyses, low eGFR was the strongest sHPT predictor, followed by young age, male sex and diabetes. Incident sHPT was associated with a 1.3-fold (95% confidence interval 1.1–1.8) increased risk of death, a 2.2-fold (1.42–3.28) higher risk of MACEs, a 5.0-fold (3.5–7.2) higher risk of CKD progression and a 1.3-fold (1.5–2.2) higher risk of fractures. Results were consistent in stratified analyses and after excluding early events. Conclusions Our findings illustrate the burden of sHPT in advanced CKD and highlight the susceptibility for adverse outcomes of patients developing sHPT. This may inform clinical decisions regarding pre-sHPT risk stratification, PTH monitoring and risk-prevention strategies post-sHPT development.

Download Full-text

Longitudinal course of GDF15 levels before acute hospitalization and death in the general population

Innovation in Aging ◽

10.1093/geroni/igab046.2507 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 669-669

Author(s):

Juliette Tavenier ◽

Ove Andersen ◽

Jan O Nehlin ◽

Janne Petersen

Keyword(s):

General Population ◽

Health Outcomes ◽

Cox Regression ◽

Serum Levels ◽

Population Based ◽

Biological Aging ◽

Acute Hospitalization ◽

Adverse Health ◽

Adverse Health Outcomes ◽

Increased Risk

Abstract Growth differentiation 15 (GDF15) is a potential novel biomarker of biological aging. To separate the effects of chronological age and birth cohort from biological age, longitudinal studies investigating associations of GDF15 levels with adverse health outcomes are needed. We investigated changes in GDF15 levels over 10 years in an age-stratified sample of the general population and their relation to the risk of acute hospitalization and death. Serum levels of GDF15 were measured three times in 5-year intervals in 2176 participants aged 30, 40, 50, or 60 years from the Danish population-based DAN-MONICA cohort. We assessed the association of single and repeated GDF15 measurements with the risk of non-traumatic acute hospitalizations. We tested whether changes in GDF15 levels over 10 years differed according to the frequency of hospitalizations within 2 years, or survival within 20 years, after the last GDF15 measurement. The change in GDF15 levels over time was dependent on age and sex. Higher GDF15 levels and a greater increase in GDF15 levels were associated with an increased risk of acute hospitalization in adjusted Cox regression analyses. Participants with more frequent admissions within 2 years, and those who died within 20 years, after the last GDF15 measurement already had elevated GDF15 levels at baseline and experienced greater increases in GDF15 levels during the study. The change in GDF15 levels was associated with changes in C-reactive protein and biomarkers of kidney, liver, and cardiac function. Monitoring of GDF15 starting in middle-age could be valuable for the prediction of adverse health outcomes.

Download Full-text

Subpopulations at increased risk of adverse health outcomes from air pollution

European Respiratory Journal ◽

10.1183/09031936.03.00402103 ◽

2003 ◽

Vol 21 (Supplement 40) ◽

pp. 57S-63s ◽

Cited By ~ 45

Author(s):

I. Annesi-Maesano ◽

N. Agabiti ◽

R. Pistelli ◽

M-F. Couilliot ◽

F. Forastiere

Keyword(s):

Air Pollution ◽

Health Outcomes ◽

Adverse Health ◽

Adverse Health Outcomes ◽

Increased Risk

Download Full-text

Historic and Modern Air Pollution Studies Conducted in Utah

Atmosphere ◽

10.3390/atmos11101094 ◽

2020 ◽

Vol 11 (10) ◽

pp. 1094

Author(s):

Judy Ou ◽

Cheryl S. Pirozzi ◽

Benjamin D. Horne ◽

Heidi A. Hanson ◽

Anne C. Kirchhoff ◽

...

Keyword(s):

Air Pollution ◽

Health Outcomes ◽

Fine Particulate Matter ◽

Ambient Air ◽

Ambient Air Pollution ◽

Atmospheric Conditions ◽

Adverse Health ◽

Adverse Health Outcomes ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk

Utah’s low-smoking population and high population density concentrated in mountain valleys, with intermittent industrial activity and frequent temperature inversions, have yielded unique opportunities to study air pollution. These studies have contributed to the understanding of the human health impacts of air pollution. The populated mountain valleys of Utah experience considerable variability in concentrations of ambient air pollution because of local emission sources that change over time and episodic atmospheric conditions that result in elevated concentrations of air pollution. Evidence from Utah studies indicates that air pollution, especially combustion-related fine particulate matter air pollution and ozone, contributes to various adverse health outcomes, including respiratory and cardiovascular morbidity and mortality and increased risk of lung cancer. The evidence suggests that air pollution may also contribute to risk of pre-term birth, pregnancy loss, school absences, and other adverse health outcomes.

Download Full-text

Adverse health outcomes in relationship to hypogonadism (HG) after platinum-based chemotherapy: A multicenter study of North American testicular cancer survivors (TCS).

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.18_suppl.lba10012 ◽

2017 ◽

Vol 35 (18_suppl) ◽

pp. LBA10012-LBA10012 ◽

Cited By ~ 3

Author(s):

Mohammad Issam Abu Zaid ◽

Alvaro G. Menendez ◽

Omar El Charif ◽

Chunkit Fung ◽

Patrick O. Monahan ◽

...

Keyword(s):

Risk Factors ◽

Health Outcomes ◽

Disease Risk ◽

Cardiovascular Disease Risk ◽

Testosterone Replacement Therapy ◽

Adverse Health ◽

Adverse Health Outcomes ◽

Risk Alleles ◽

Platinum Based Chemotherapy ◽

Increased Risk

LBA10012 Background: HG affects a substantial percentage of TCS and can contribute to significant morbidity, but few studies have examined the relationship between HG and adverse health outcomes (AHO), taking into account genetic variation. Methods: Eligible TCS were < 55 y at diagnosis and treated with only first line chemotherapy after 1990. TCS underwent physical exams and genotyping, and completed questionnaires regarding 16 AHO and health behaviors. HG was defined as serum testosterone ≤ 3.0 ng/mL or the use of testosterone replacement therapy. Results: We evaluated 491 TCS. Median age at evaluation was 38 y (range 19-68). 38.5% had HG. Two SNPs in the sex-hormone-binding globulin ( SHBG) locus previously implicated in increased HG risk in the general population (Ohlsson et al, PLOS Genetics 2011) displayed effect sizes consistent with prior reports (rs6258, OR = 1.3; rs12150660, OR = 0.79), but were not statistically significant. However, TCS with ≥ 2 risk alleles for the two SNPs in the SHBG locus vs no risk alleles had 2-fold increased risk for HG (OR = 2.2, P = .12). Multivariate analysis identified risk factors for HG including: age (OR = 1.4 per 10 year increase, P = .007), and BMI ≥ 25 kg/m2 (OR = 2.2, P = .003). Vigorous-intensity physical activity appeared protective (OR = 0.6, P = .06). Type of chemotherapy regimen and socioeconomic factors did not correlate with HG. Only 35% of TCS with HG vs 49% of those without HG reported none or 1 AHO ( P = .003). TCS with HG were more likely to take medications for dyslipidemia (20% vs 6%, P < .001), hypertension (19% vs 11%, P = .01), erectile dysfunction (ED) (20% vs 12%, P = .02), diabetes (6% vs 3%, P = .07), or anxiety/depression (15% vs 10%, P = 0.06) compared to TCS with normal levels, and also to have peripheral neuropathy (PN) (31% vs 23%, P = .04). HG status did not correlate with oto- or renal toxicity. Conclusions: Over a third of TCS have HG at a relatively young age. HG was associated with increased cardiovascular disease risk factors, ED, and PN. SHBG polymorphisms appear important in TCS, but our study was underpowered to confirm an association. Providers should screen TCS for HG and treat those who are symptomatic.

Download Full-text