Cardiovascular risk factors and body composition in adults with achondroplasia

Svein Fredwall, MD, Ph.D., expert working on TRS National Resource Centre for Rare Disorders, Sunnaas Rehabilitation Hospital, in Norway, has been publishing relevant research in Skeletal Dysplasia, in particular, on the effects and impact achondroplasia has on adults. This article data is based on the ongoing project 'The Norwegian Adult Achondroplasia Study'.

The aim of this study was to investigate cardiovascular risk factors and body composition in adults with achondroplasia, as obesity is a common concern in this population. 
There are no established standards for evaluating obesity in adults with achondroplasia yet Magnetic resonance (MRI) was used and can be applied for these evaluations.

Obesity is associated with hypertension, dyslipidemia (abnormal amount of lipids or fat in the blood), and type 2 diabetes, it can lead to cardiovascular disease (CVD) and increased mortality. Adults with achondroplasia frequently present a body mass index (BMI) in the obesity range, with a predisposition to abdominal obesity. ¹

This study had the support of 49 participants with achondroplasia, that had their body measurements as clinical, and laboratory assessments. Also, 40 completed magnetic resonance imaging (MRI) for body composition analysis. There were also 98 control participants, matched for body mass index (BMI), sex, and age.

 

What is BMI?

The BMI is a height-dependent index and it can tend to overestimate body fat mass in achondroplasia patients. The BMI should be used with other complementary anthropometric measures since it does not allow quantifying fat mass or its distribution in the body. A recently published study found a strong correlation between BMI and waist circumference and describes a high prevalence of abdominal obesity that increases with age and a more sedentary lifestyle, in its group of Norwegian adults with achondroplasia. However, it concluded that it is necessary to continue investigating body composition, fat distribution, and its clinical implications in these people, as well as the influence that physical activity can have on these factors.²

Participants were well matched for BMI and sex, but achondroplasia participants were younger than controls (mean age 41.1 versus 54.3 years). 

Comparing results from adults with achondroplasia with adult controls, adults with achondroplasia had lower:
> Age-adjusted mean blood pressure
> Total and low-density lipoprotein (LDL) cholesterol and triglycerides
> Age-adjusted mean visceral fat store (1.9 Ach versus 5.30 Liters controls)
> Abdominal subcutaneous fat (6.0 Ach versus 11.2 Liters Controls)
> Liver fat (2.2 Ach versus 6.9% Controls)


Figure 2. Body composition in four different individuals with achondroplasia. Credits: Fredwall S et al, 2020

In figure 2, the visceral (inside the abdomen) fat tissue is shown in red while the abdominal subcutaneous fat tissue is in blue. Individuals B, C, and D had increased muscle fat infiltration also.

In the study, the average BMI was 33.3 kg/m², ranging from 22 to 50 kg/m². Obesity is considered when the BMI is higher than 30 kg/m²  and it was found in 67% of the participants with achondroplasia, having 18% of the participants' severe obesity (BMI ≥ 40 kg/m²).¹
In an article by Hoover-Fong, 2019, in a US population study, 56% of the men and 35% of the women with achondroplasia had hypertension.⁴

The body composition profile in the achondroplasia group indicated a low propensity of developing type 2 diabetes and cardiovascular disease, in contrast to the BMI-matched controls.  So despite a high BMI, the cardiovascular risks appeared similar or lower in achondroplasia compared with controls, indicating that other factors might contribute to the increased mortality observed in this condition. 1

These findings are consistent with the study by Owen et al., who found low triglyceride and glucose levels in 32 adults with achondroplasia. These findings are also consistent with the study in mice with achondroplasia that developed abdominal obesity yet, it was not associated with diabetes or dyslipidemia.³ 

In this study, only 3 individuals with achondroplasia had type 2 diabetes, all with BMIs ≥43 kg/m² and waist circumferences ≥107 centimeters, so had severe obesity. 

The results indicate that metabolic complications can occur in achondroplasia in those with very high BMI and waist circumference. So, to avoid reaching this point is key to keep a healthy diet, and maintaining regular physical activity, which is applicable to all people, with or without achondroplasia, to prevent excessive weight gain.

The cardiovascular risk pattern and metabolism in achondroplasia are still not fully understood, yet the innovative medicines in ongoing pediatric trials in achondroplasia might also modify the metabolic profiles and body composition in achondroplasia, as demonstrated in the mouse model. ³

Key conclusions¹: 
1. The cardiovascular risks appeared similar or lower in achondroplasia compared with controls, indicating that there might be other factors contributing to the increased mortality observed in this condition.
2. BMI is not a clinically useful measure to assess cardiovascular risks in adults with achondroplasia.