Mark L. Fuerst

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(1) Inflammatory diseases raise risk of venous thromboembolism; (2) antiphospholipid antibodies play a role in MI; (3) persistent hyperuricemia predicts mortality.

CV Risk in Rheumatic Disease

Besides bone mineral density (BMD), other bone characteristics can be used to determine fracture risk, according to a 

.
	
	The results show low BMD is not the only cause of bone fragility, and the majority of older adults who sustain a fragility fracture do not meet the diagnostic criteria for osteoporosis.
	
	“Older women are at particularly high risk of fracture. In fact, the number of women who will experience a fragility fracture in any given year exceeds the number who will experience a first-time stroke, breast cancer, or myocardial infarction combined,” said co-lead author Mary L. Bouxsein, PhD, Director of the Center for Advanced Orthopedic Studies at Beth Israel Deaconess Medical Center, Boston, Massachusetts. “Improved methods to identify those in whom fractures are common but whom standard clinical testing does not identify as high risk would allow us to target treatment to this important group and ultimately reduce fracture burden.”

BMD assessed by dual-energy x-ray absorptiometry is the clinical standard for determining fracture risk. The majority of older adults who sustain a fracture, however, have T scores greater than −2.5. Therefore, they do not meet the clinical criteria for osteoporosis, the researchers noted. Importantly, bone fragility is due to low BMD and deterioration in bone structure.
	
	Bouxsein and colleagues assessed whether indices of high-resolution peripheral quantitative computed tomography (CT) were associated with fracture risk independently of femoral neck BMD and the Fracture Risk Assessment Tool (FRAX) score. They assessed 7254 participants, mean baseline age 69 years, in 8 cohorts from the US, France, Switzerland, Canada, and Sweden.
	
	Over a mean follow-up of 4.63 years, 8% of participants met the diagnostic criteria for osteoporosis, yet 11% of participants had incident fractures. Some 633 (86%) participants had femoral neck T scores greater than −2.5.

Those who experienced fracture were more likely to be older, female, have a lower BMI, use osteoporosis medications, and have a previous fracture. Participants who sustained fractures had worse bone measurements for nearly all parameters vs those who did not fracture.
	
	Several measures of bone density and structure at different sites on the bone, including the density of the compact bone tissue and the thickness of the spongy bone tissue at the wrist, were predictive of fracture. Other fractures risks included an increase in tibia cortical porosity and decrease in radius trabecular volumetric bone density. Failure load was the bone characteristic most strongly associated with risk of fracture.

The researchers concluded that high-resolution CT results and failure load improved prediction of fracture beyond femoral neck BMD or FRAX scores alone. “Results from this large international cohort of women and men suggest deficits in density and structure throughout the bone contribute to fracture risk independently of BMD and current risk assessment tools,” said lead author Lisa Samelson, PhD, an epidemiologist at Harvard Medical School, Boston, Massachusetts. “Further, assessment of these bone characteristics may be useful in those who would not otherwise be identified as being at high risk for fracture.”

Samelson EJ, Broe KE, Xu H, et al. Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study. Lancet Diabetes Endocrinol. 2019;7:34-43. 

Articles

Which additional bone traits, besides bone mineral density, can be used to determine fracture risk? Authors of a new study sought to find out.

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Overtreating patients for hypothyroidism could raise their risk of atrial fibrillation (AF), and by association, their risk of stroke, according to a new study.

The results show elevated levels of the thyroid hormone free thyroxine even within the upper levels of normal reference ranges were associated with an increased risk of AF, which suggests the possible need to redefine the safest reference ranges in hypothyroidism treatment.

“We know patients with hypothyroidism have a higher risk of atrial fibrillation, but we didn’t consider increased risk within what’s considered the normal range of thyroid hormones. These findings show we might want to re-consider what we call normal,” said lead author Jeffrey L. Anderson, MD, Distinguished Clinical and Research Physician at the Intermountain Medical Center Heart Institute.
	Anderson presented the data at the American Heart Association Scientific Session conference in Chicago.

The researchers surveyed the electronic medical records of 174 914 patients, mean age 63.8 years, treated at Intermountain Healthcare facilities whose free thyroxine levels were recorded and who were not on thyroid replacement medication. They took what is considered a normal range of free thyroxine levels, divided it into four quartiles, and looked at those patients’ records for a current or future diagnosis of AF.

After a mean follow-up of 6.3 years, they found 7.4% of the patients had free thyroxine levels below the normal reference range, 88.4% had levels in the normal range, and 4.2% had levels above the normal range. After adjustment, the relative risk of prevalent AF was 40% higher for patients in the highest quartile of free thyroxine levels vs patients in the lowest quartile, which translated into a 16% increase in newly developing AF during follow up.

After adjustment, the relative risk of prevalent AF was 40% higher for patients in the highest quartile of free thyroxine levels vs patients in the lowest quartile, which translated into a 16% increase in newly developing AF during follow up.

This suggests, said Anderson, that the optimal healthy range of free thyroxine should be reconsidered and redefined. “Thyroid hormones are associated with losing weight and having more energy, which may lead to people being treated at the high end of the normal range,” he said. “Are we harming people by putting them at a higher risk of atrial fibrillation, and therefore stroke?”

The study also found that free thyroxine should be measured, along with thyroid-stimulating hormone, which is more commonly tested for in patients with irregular thyroid hormone levels, but was not helpful within the normal range in refining risk.

The link between free thyroxine levels and AF was recently recognized in the 

, a population-based cohort study first started in 1990. The new study replicates the results in a much larger population and establishes the link between free thyroxine levels and AF among patients treated in the United States.

“The next step for researchers is to conduct a randomized trial to see if targeting a lower versus a higher upper range of free thyroxine in patients receiving thyroid hormone replacement therapy leads to a lower risk of atrial fibrillation and stroke along with other possible heart-related issues, like atherosclerosis,” said Anderson.

: Anderson JL, et al. Poster Sa1208. Presented at: American Heart Association Scientific Sessions; Nov. 10-12, 2018; Chicago.

A new study found that elevated free thyroxine within the upper range of normal may increase risk of AF; is may be time to redefine what is "safe" when treating hypothyroidism.