New Risk Factors for Diastolic Dysfunction Identified in Study

Lindsey Shapiro, PhD avatar

by Lindsey Shapiro, PhD |

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Several risk factors for diastolic dysfunction (DD), the heart’s inability to fill with blood properly after it beats, were identified in people with systemic sclerosis (SSc) in a recent study.

These risk factors, such as obesity, could be potentially modified to reduce the occurrence of more serious disease outcomes, including a higher mortality risk, researchers suggested.

The study, “Diastolic Dysfunction in Systemic Sclerosis: Risk Factors and Impact on Mortality,” was published in the journal Arthritis and Rheumatology.

DD results from a stiffening of the left ventricle, the heart chamber responsible for pumping blood to the rest of the body. Over time, increases in cardiac pressure, irregular heartbeat (arrhythmia), and enlargement of the heart chambers, all caused by DD, can lead to heart failure.

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Although DD can be caused by a number of medical conditions, the excess of scar tissue commonly observed in SSc sometimes accumulates in the heart, making these patients particularly susceptible.

“Given the increased risk of mortality in SSc patients with DD, it is important to improve comprehensive identification of potentially modifiable risks,” the researchers wrote.

While some DD contributors have been identified in the general population — including older age, hypertension, obesity, diabetes, and coronary artery disease, among others — few SSc-specific risk factors have been discovered. This could be due to low patient numbers and inconsistent criteria for defining DD across studies.

Now, researchers at the Mayo Clinic in Rochester, Minnesota, and Johns Hopkins University collected clinical data at six-month intervals from 806 SSc patients enrolled in the Johns Hopkins Scleroderma Center Cohort. All patients had undergone at least one 2D echocardiogram (2DE) — a test used to diagnose DD — between 2006 and 2017.

Of the 806 enrolled patients, 84% were female and 70% were Caucasian. The participants’ median age at the time of their most recent 2DE scan was 58.4.

DD was present in 18.6% of the participants — 150 had DD, 118 had indeterminate diastolic function, and 538 had normal diastolic function.

The researchers developed a multivariable model to determine which known risk factors (those observed even in non-SSc populations) and SSc clinical characteristics pose significant risk for DD development.

Overall, multiple SSc characteristics were determined to be risk factors for DD, including a longer disease duration.

Reduced diffusing capacity of the lung for carbon monoxide (DLCO), a measure of the lungs’ ability to transfer oxygen to the blood, was also associated with DD. According to the researchers, this could indicate pulmonary vascular disease in these patients, although not enough data were collected in this study to determine that.

The third observed risk factor was scleroderma renal crisis (SRC), the acute onset of high blood pressure and kidney failure in people with SSc. SRC and myocardial stiffness, a feature of DD, share some common disease processes, so it makes sense that SRC would be a risk factor, the researchers wrote.

The presence of anti-Scl70 antibodies, an immune system protein used to diagnose SSc and other connective tissue disorders, was associated with a decreased risk of DD. A history of severe gastrointestinal disease also reduced DD risk. The authors hypothesize that this effect could be mediated by a decrease in adipose, or fat tissue, resulting in lower levels of inflammatory mediators.

Additionally, of the known DD risk factors, only older age, obesity, and coronary artery disease (CAD, a form of heart disease) were significantly associated with DD on the final multivariable analysis.

The team noted that at least one traditional DD risk factor was present in 97% (146 out of 150) of participants with DD.

Researchers then investigated the impact of DD on mortality rates. Among 672 SSc patients with either DD or normal function, 135 deaths were reported.

After adjusting the data for traditional DD risk factors and using the final multivariable model, the team found that DD itself was independently associated with an increased mortality risk — a 69% increase in mortality compared with SSc patients without DD.

Age-adjusted five- and 10-year survival rates for SSc patients with DD were 40.8% and 30.5%, respectively. In patients with normal diastolic function, the age-adjusted five- and 10-year survival was 68.9% and 61.1%, respectively.

The team noted, however, that these results are “limited by examination of a single 2DE per participant. Therefore, while important associations can be made regarding risk factors for prevalent DD, a cause and effect relationship should not be extrapolated,” they wrote.

Nevertheless, “potentially modifiable risk factors, including CAD and obesity, should be addressed in patients with SSc to reduce mortality risk,” the team concluded.