Patrick Campbell

An analysis of data from the Cleveland Clinic Echocardiography database is sounding the alarm on the potential impact of calcium supplementation in older adults with aortic stenosis.

A retrospective longitudinal study with data from more than 2500 patients followed for nearly 70 months, results of the study indicate calcium supplementation was associated with a 31% greater risk of mortality and a 48% greater risk of aortic valve replacement among older adults with aortic stenosis.

“Strengthened by its large sample size and extended follow-up period, our study suggests that calcium supplementation does not confer any cardiovascular benefit, and instead may reflect an elevated overall risk of aortic valve replacement and mortality, especially in those not undergoing aortic valve replacement,” wrote investigators.

With calcium and vitamin D among the most commonly supplemented vitamins and minerals among aging populations, particularly those at 

, the current study was designed by investigators at the Cleveland Clinic Foundation to assess the impact of supplemental calcium and vitamin D on mortality and progression of aortic stenosis. With this in mind, investigators designed their study as a retrospective longitudinal study of patients aged 60 years and older with mild-moderate native aortic stenosis from the Cleveland Clinic Echocardiography database from 2008-2016.

From this search, investigators identified 2657 patients for inclusion in their analyses. These patients had a mean age of 74 years, 42% were women, and the median follow-up duration was 69 months. Patients included in the analyses were stratified into groups defined by the absence of supplementation, supplementation with vitamin D alone, and supplementation with calcium plus vitamin D. Of the 2657 patients included, 49% did not supplement, 12% supplemented with vitamin D alone, and 39% supplemented with calcium and vitamin D.

The primary outcomes of interest for the investigators’ analyses were mortality and aortic valve replacement. Of note, mortality was assessed as all-cause mortality, cardiovascular mortality, and non-cardiovascular mortality. Secondary outcomes of interest included aortic stenosis progression by aortic valve area and peak/mean gradients. investigators pointed out primary outcomes were assessed through survival analyses with Kaplan-Meier nonparametric method.

Overall, there were 540 deaths that occurred among the study cohort, with 150 being classified as cardiovascular death, 155 classified as noncardiovascular death, 235 were deaths of unknown etiology. A total of 774 cases of aortic valve replacement were identified during the follow-up period.

Results of the investigators’ analyses indicated supplementation with calcium and vitamin D was associated with a significantly higher risk of all-cause mortality (absolute rate [AR]=43.0/1000 person-years; HR=1.31, [95% CI, 1.07-1.62]; 

=.009), cardiovascular mortality (AR, 13.7/1000 person-years; HR, 2.0 [95% CI, 1.31-3.07]; 

=.001), and aortic valve replacement (AR, 88.2/1000 person-years; HR, 1.48 [95% CI, 1.24-1.78]; 

 <.001) compared to the nonsupplementation arm. investigators noted the increased risk of all-cause mortality was greater among those supplementing with calcium and vitamin D when compared against those supplementing vitamin D alone as well (

Investigators pointed out analysis of those who supplemented with calcium alone, which was a cohort of 115 patients, indicated these individuals experienced a similar rate of all-cause mortality (HR, 1.24 [95% CI, 0.77-1.99]; 

=.38) but a higher risk of aortic valve replacement (HR, 2.7 [95% CI, 1.76-4.08]; 

, Jutta Bergler-Klein, a professor of the Medical University of Vienna, detailed the contemporary trends in supplement use among older patients, but added clinicians may need to rethink the potential risk posed by calcium supplements in those with osteoporosis at high risk for cardiovascular disease.

“In patients with calcific aortic stenosis and high-risk cardiovascular disease, the present study strongly adds to the evidence that long-term continuous calcium supplementation should be avoided if not mandatory,” wrote Bergler-Klein.

Supplemental calcium and vitamin D and long-term mortality in aortic stenosis,

This article was initially published by our sister publication Endocrinology Network.

Articles

An analysis of data from a Cleveland Clinic database indicates calcium supplementation in older adults with aortic stenosis was linked to an increased risk of mortality and worsening aortic stenosis.

Calcium supplementation could increase risk of death in older adults with cardiovascular disease

Common treatments for infertility could be accompanied by an increased risk of in-hospital complications and other adverse pregnancy outcomes, according to the results of a new study.

An analysis comparing deliveries of children conceived with and without assisted reproductive therapy (ART), results of the analysis suggest conception with ART was independently associated with 1.7- and 2.5-fold increased risks for arrhythmia and acute kidney injury, respectively, after adjustment for baseline risk profile.

“We were surprised that assisted reproductive technology was independently associated with these complications, as opposed to being associated with only the existence of pre-existing health conditions or only among older women undergoing infertility treatment,” said lead investigator Pensée Wu, MBChB, MD, senior lecturer and honorary consultant obstetrician and subspecialist in Maternal Fetal Medicine at Keele University School of Medicine in Staffordshire, United Kingdom, 

Published on February 22, the study is part of a special Go Red for Women issue of the 

Journal of the American Heart Association

. Citing knowledge gaps related to risk of in-hospital complications following pregnancies conceived by ART, Wu and a team of colleagues designed the study as a retrospective analysis of pregnancies within the US National Inpatient Sample database. Including all women admitted for delivery from 2008-2016, investigators identified an unweighted cohort of 7,236,075 deliveries, which was weighted to represent 106,248 deliveries conceived by ART and 34,167,246 deliveries conceived without ART.

For the purpose of analysis, investigators used binary logistic regression adjusted for age, median ZIP code income quartile, primary payer, race and ethnicity, weekday admission, year of admission, and comorbidities associated with cardiovascular disease to assess associations of ART with maternal and obstetric outcomes. Investigators noted plans for temporal analyses with pregnancies stratified by year, with groups defined as 2008-2010, 2011-2013, and 2014-2016.

Over the study period, the percentage of delivery episodes from ART increased from 0.05% in 2008 to 0.51% in 2016 (

 <.001). Compared to those who did not conceive with ART, women who conceived by ART were older (median age: 35 vs 28 years; 

 <.0001), more likely to be White women (66.13% vs 47.82%; 

 <.0001), and more likely to be in the wealthiest quartile of household income (54.63% vs 21.42%; 

Results of the investigators’ analyses indicated ART-conceived pregnancies were independently associated with increased risk of acute kidney injury (aOR, 2.52 [95% CI 1.99-3.19]; 

 <.0001) and arrhythmia (aOR, 1.65 [95% CI, 1.46-1.86]; 

 <.0001). ART-conceived pregnancies were also independently associated with increased risk of adverse obstetric outcomes, including placental abruption (aOR, 1.57 [95% CI, 1.41–1.74]; 

 <.0001), cesarean delivery (aOR, 1.38 [95% CI, 1.33-1.43]; 

 <.0001) and preterm birth (aOR, 1.26 [95% CI, 1.20-1.32]; 

 <.0001). Investigators pointed out consistent trends were observed across subgroups without cardiovascular disease risk factors or without multifetal pregnancies. Investigators also noted the results demonstrated women who conceived with ART incurred higher hospital charges than those who conceived without ART ($18,705 vs $11,983; 

“Especially patients with existing cardiovascular risk factors should be counseled about the potentially long-term cardiovascular implications and risks associated with ART,” Wu added. “It’s important for women to know that assisted reproductive technology carries a higher risk of pregnancy complications, which require close monitoring, particularly during delivery. Primary and specialist health care professionals should ensure these risks are communicated and strategies to mitigate them are discussed and implemented.”

In-Hospital Complications in Pregnancies Conceived by Assisted Reproductive Technology,

Journal of the American Heart Association.

New research suggests pregnancies conceived with assisted reproductive technology were associated with a more than doubling in risk for acute kidney injury.

Infertility treatments could raise risk of acute kidney injury, heart rhythm disorders

Long or irregular periods could signal an increased risk for nonalcoholic fatty liver disease (NAFLD), according to the results of a recent study.

A cross-sectional study of more than 70,000 women younger than 40 years of age, results of the study demonstrate women with long or irregular menstrual cycles were at a 22% greater risk of NAFLD compared to the study’s reference group, with this increase in risk ballooning to nearly 50% in time-dependent analysis.

“Our study results show that long or irregular menstrual cycles may be associated with an increased risk of developing NAFLD, and this link was not explained by obesity,” said Seungho Ryu, MD, PhD, of the Center for Cohort Studies, Total Healthcare Center, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine in Seoul, South Korea, 

. “Previous studies have shown that long or irregular menstrual cycles are associated with type 2 diabetes and cardiovascular disease, but our study is the first to find a link between long or irregular menstrual cycles and NAFLD.”

Although research has established definitive associations between presence of long or irregular menstrual cycles in women with increased risk of type 2 diabetes and cardiovascular disease, less is known about potential associations with NAFLD. To develop a better understanding of this association, investigators designed a cross-sectional study of data from Kangbuk Samsung Health Study, which consists of premenopausal Korean women younger than 40 years of age who underwent annual or biennial health examinations from 2011-2017.

Funded by the Sungkyunkwan University and the Southampton NIHR Biomedical Research Centre, the study’s cross-sectional analyses included 72,092 women and the longitudinal assessments included a subset of 51,118 women without NAFLD at baseline. Of the 72,092 women included in the cross-sectional analyses, 7.1% had NAFLD at baseline and 27.7% had long or irregular menstrual cycles.

For the purpose of analysis, long or irregular cycles were defined as menstrual cycles of 40 days or longer or too irregular to estimate and abdominal ultrasonography was performed to identify NAFLD. Investigators used multivariable Cox proportional hazard regression analyses to estimate hazard ratios for incident NAFLD according to menstrual cycle regularity and length, with 26–30-day cycles as the reference.

During a median follow-up of 4.4 years, incident NAFLD occurred in 8.9% of women. In the investigators’ analyses, long or irregular menstrual cycles were positively associated with prevalent NAFLD. Specifically, the risk for NAFLD among those with long or irregular menstrual cycles was 22% greater than that observed for the reference group after adjustment for age, BMI, insulin resistance, and other confounders (HR, 1.22; 955 CI, 1.14-1.31). Investigators pointed out this association strengthened in time-dependent analysis, with a 49% increase in risk compared to the reference group (HR, 1.49; 95% CI, 1.38-1.60)

“Young women with long or irregular menstrual cycles may benefit from lifestyle changes to reduce the risk of NAFLD as well as other cardiometabolic diseases,” Ryu added.

Long or Irregular Menstrual Cycles and Risk of Prevalent and Incident Non-Alcoholic Fatty Liver Disease

Journal of Clinical Endocrinology and Metabolism.

This article was initally published by our sister publication Endocrinology Network.

A cross-sectional study of more than 70k women suggests those with long or irregular menstrual cycles were at a 22% greater risk of NAFLD.

Long, irregular periods linked to increased risk of NAFLD

New research from investigators at the University of Michigan suggests exposure to per- and polyfluoroalkyl substances (PFAS) was associated with an increased risk of developing diabetes in midlife among women.

An analysis of data from more than 1200 women in the Study of Women’s Health Across the Nation Multi-Pollutant Study (SWAN-MPS), results provide evidence demonstrating women in the highest tertile of PFAS exposure were at a more than 2-fold increase in risk of developing incident diabetes compared to their counterparts in the lowest tertile of exposure.

“Higher serum concentrations of certain PFAS were associated with higher risk of incident diabetes in midlife women,” wrote investigators. “The joint effects of PFAS mixtures were greater than those for individual PFAS, suggesting a potential additive or synergistic effect of multiple PFAS on diabetes risk”.

In recent years, the interest in the long-term impact of exposure to PFAS has grown. A group of more than 4700 synthetic chemicals found in a wide range of consumer products, including cookware and cosmetic products, recent studies suggest exposure to these chemicals were associated with a negative impact on cardiometabolic health profiles. As such, Sung Kyun Park, ScD, MPH, and a team of colleagues from the Department of Epidemiology at University of Michigan School of Public Health designed the current study with an interest in assessing the impact of PFAS exposure on risk of incident diabetes.

With this in mind, investigators designed their study to assess potential associations between serum PFAS concentrations and incident diabetes using data from SWAN-MPS. A substudy of the multicenter, community-based, prospective SWAN study, SWAN-MPS was launch in 2016 to evaluate the roles of environmental pollutants in chronic diseases during and after the menopausal transition. From the study, investigators obtained data from 1400 women with stored blood and urine samples from the 3302-woman cohort included in the original study.

After exclusion of those with diabetes at baseline and those with insufficient data for analysis, investigators had identified a cohort of 1237 women for inclusion in their analyses. This cohort had a median age of 49.4 years, 17,005 person-years of follow-up, and 102 women who developed incident diabetes during the follow-up.

For the purpose of analysis, investigators assessed associations of incident diabetes with serum concentrations of 7 PFAS with high detection rates, which was defined as greater than 96% detection rate, in Cox proportional hazards models adjusted for race/ethnicity, site, education, smoking status, alcohol consumption, total energy intake, physical activity, menopausal status and BMI. The 7 PFAS of interest were n-PFOA, PFNA, PFHxS, n-PFOS, Sm-PFOS, MeFOSAA, and EtFOSAA.

Upon analysis, results indicated an increased risk of incident diabetes was observed for those in the highest tertile of for n-PFOA (HR, 1.67 [95% CI, 1.21-2.31]; 

=.001), for PFHxS (HR, 1.58 [95% CI, 1.13-2.21]; 

=.003), for Sm-PFOS (HR, 1.36 [95% CI, 0.97-1.90]; 

=.05), for MeFOSAA (HR, 1.85 [95% CI, 1.28-2.67]; 

.0004), and for the sum of 4 common PFAS (HR, 1.64 [95% CI, 1.17-2.31]; 

=.002) compared to those in the lowest tertiles for each category. When assessing exposure to the 7 PFAS of interest as mixtures, those in the highest tertile of exposure were at a more than 2-fold greater risk of developing incident diabetes compared to those in the lowest tertile of exposure (HR, 2.62 [95% CI, 1.12-6.20]).

“Reduced exposure to these ‘forever and everywhere chemicals’ even before entering midlife may be a key preventative approach to lowering the risk of diabetes. Policy changes around drinking water and consumer products could prevent population-wide exposure,” investigators added.

Per- and polyfluoroalkyl substances and incident diabetes in midlife women: the Study of Women’s Health Across the Nation (SWAN)

Data from an analysis of a SWAN substudy suggests increased exposure to PFAS was linked to an increased risk of incident diabetes during midlife among women.

Exposure to PFAS increases risk of diabetes in midlife women

With bone loss is a chief concern among aging women, investigators used data from the Study of Women’s Health Across the Nation (SWAN) study, which is supported by the National Institutes of Health, and determined every 50% decrement in anti-Mullerian hormone levels was associated with additional declines in spine bone mineral density (BMD) ranging from 0.22-0.50% among women between premenopausal, perimenopause, and late perimenopause.

“To be able to intervene and reduce the rate and amount of bone loss, we need to know if this loss is imminent or already ongoing,” said the lead investigator Arun Karlamangla, MD, a professor of medicine in the division of geriatrics at the David Geffen School of Medicine at UCLA, in a statement. “We do not reliably know before it actually happens when a woman’s last menstrual period will be, so we cannot tell whether it is time to do something about bone loss.”

Together with a team of colleagues from the David Geffen School of Medicine at UCLA, Karlamangla designed the current study with the intent of assessing potential predictors of bone loss among women during the menopause transition or immediately before entering menopause. With this in mind, investigators conducted their study to test the hypothesis that low circulating levels of anti-Mullerian hormone were associated with future and ongoing bone loss. A multisite, longitudinal prospective cohort study of the menopause transition, the SWAN study provided investigators with data related to more than 3000 women enrolled at 7 sites between January 1996 and December 1997.

Leveraging this data, investigators designed their study to assess the impact of every 50% decrement in anti-Mullerian hormone level in premenopause, early perimenopause, and in late perimenopause with adjustment for age, BMI, race/ethnicity, and study site.

Upon analysis, results indicated each 50% decrement in anti-Mullerian hormone level was associated with a 0.14% per year feaster decline over the next 3-4 years in lumbar spine BMD and a 0.11% per year faster decline in femoral neck BMD (

 <.001 for both). In contrast, no association was observed between anti-Mullerian hormone levels in late perimenopause and rate of future BMD decline.

Additionally, results indicated anti-Mullerian hormone levels were also associated with magnitude of ongoing bone loss when measured as a percent of peak BMD lost by end of the next 2-3 years. Further analysis suggested each 50% decrement in anti-Mullerian hormone level was associated with a 0.22% additional loss in spine BMD in premenopause, 0.43% additional loss in early perimenopause, and 0.50% additional loss in late perimenopause (

“These findings make feasible the designing and testing of midlife interventions to prevent or delay osteoporosis in women,” authors wrote.

This study, “Anti-Mullerian Hormone as Predictor of Future and Ongoing Bone Loss During the Menopause Transition,” was published in the 

This article was originally published on Endocrinology Network®. 

New research from the University of California Los Angeles (UCLA) suggests assessments of anti-Mullerian hormone levels could help clinicians predict or detect bone loss among premenopausal women.

Anti-mullerian hormone premenopause can predict bone loss risk later in life

Results of a retrospective cohort study of more than 100,000 pregnant women suggest a history of spontaneous or induced abortion was associated with a subsequent increase in risk of developing gestational diabetes.

An analysis of data from 102,259 pregnant women receiving care at a tertiary hospital in Shanghai, results suggest women with a history of spontaneous abortion were at an 18% greater risk of gestational diabetes, but no increased risk was observed for history of induced abortion. Investigators purport the results underline the need for increased monitoring and prevention strategies among women with a history of abortion.

“Our findings suggest that pregnant women with a history of spontaneous abortion, especially those with a history of recurrent spontaneous abortion, should attend more antenatal visits to monitor their blood glucose and implement early prevention and intervention,” investigators wrote. “Considering the short- and long-term adverse effects of gestational diabetes on both mothers and their offspring, our findings may also have potential public health implications.”

With the burden of gestational diabetes continuing to balloon and previous studies linking spontaneous abortion and induced abortion to increased risk of metabolic disease, investigators from the School of Medicine at Tongji University sought to assess whether spontaneous or induced abortion, as a composite and individually, were associated with increased risk of gestational diabetes. With this in mind, investigators designed a retrospective cohort study of pregnant women who registered in the outpatient clinics of the department of obstetrics at a tertiary hospital in Shanghai, China and visited the clinic regularly from January 2014-December 2019.

A total of 125,430 registered women were identified from the investigators’ initial query. Of these, 102,259 were included in the final analytical cohort, which included 65,728 with no abortion history, 14,579 with spontaneous abortion experience only, 17,935 with induced abortion experience only, and 4017 with both spontaneous abortion and induced abortion experience. Overall, 12,153 cases of gestational diabetes were identified, with a prevalence rate of 11.9%.

The mean age of the overall study cohort was 29.8 (SD, 3.8) years. Compared to their counterparts without a history of abortion, those with abortion history were more likely to be multiparous, more likely to have obesity, and the proportion of pregnant women older than 35 years was more than 2-fold greater among pregnant women with abortion history than those with no abortion history.

The primary outcome of interest was a diagnosis of gestational diabetes, which was screened for and diagnosed at 24-28 weeks of gestation using a 75-g diagnostic oral glucose tolerance test. Investigators planned to use a multivariable-adjusted log-binomial analysis to estimate relative risk of gestational diabetes associated with history of abortion.

Upon analysis, investigators found women who experienced only spontaneous abortion (RR, 1.25 [95% CI, 1.18-1.31]) or both spontaneous abortion and induced abortion (RR, 1.15 [955 CI, 1.05-1.27]) were at an elevated risk for development of gestational diabetes. Further analysis indicated the association between history of spontaneous abortion and gestational diabetes appeared to occur in a number-dependent manner. Specifically, compared to their counterparts with no history of abortion, a single spontaneous abortion was associated with an 18% greater relative risk of gestational diabetes (Rr, 1.18 [95% CI, 1.11-1.26]), 2 spontaneous abortions were associated with a 41% increase (RR, 1.41 [95% CI, 1.27-1.57]), and more than 2 spontaneous abortions was associated with a 43% increase in risk (RR, 1.43 [95% CI, 1.22-1.67]). Investigators noted no associations were observed for history of induced abortion only with increased risk of gestational diabetes.

Investigators pointed out multiple limitations hinder the applicability of study results to clinical practice. These limitations included reliance on self-reported data for spontaneous abortion history, reliance on data from pregnant women in China, and potential for residual confounding from unmeasured or unknown confounders.

This article originally appeared on Endocrinology Network®. 

Association of History of Spontaneous or Induced Abortion With Subsequent Risk of Gestational Diabetes

An analysis of data from more than 100k pregnant women suggests a history of spontaneous abortion was associated with an 18% increase in risk of subsequent gestational diabetes, with a history of multiple spontaneous abortions associated with an even greater risk.