▎ WuXi AppTec content team editor
Atherosclerotic cardiovascular disease (ASCVD) is one of the biggest threats to global public health, with a high incidence and youthful trend. Previous studies have confirmed that abnormally elevated circulatory levels of "apolipoprotein B (apoB)" circulation are a key cause of atherosclerosis, and atherosclerosis is likely to occur regardless of age.
Recently, Nature Reviews Cardiology, a sub-journal of Nature, published a blockbuster review, pointing out that childhood exposure to cardiovascular risk factors is prone to preclinical atherosclerotic phenotypes in adulthood, increasing the risk of cardiovascular disease-related events.
The paper points out that effectively identifying children at high risk of ASCVD and young adults with relevant preclinical signs, and using reasonable strategies to intervene and manage from the level of the overall population, will become an important exploration direction for the prevention of the global pandemic of ASCVD!
Screenshot source: Nature Reviews Cardiology
Arteriosclerosis, which begins in childhood
Elevated serum levels of apoB lipoprotein (approximated by LDL-C detection) are key causes of ASCVD. Over the past 20 years, evidence from a large number of cohort studies suggests that childhood exposure to cardiovascular risk factors can promote the formation of a preclinical atherosclerotic phenotype in adulthood, affecting the thickness or plaque of the carotid intima, coronary artery calcification score, vascular elasticity, and endothelial function.
These risk factors include dyslipidemia in childhood, obesity, metabolic syndrome, elevated blood pressure, active and passive smoking, low serum adiponectin levels, mental health deficiency, physical activity deficiency, and poor diet.
Not only that, but we can even detect early atherosclerotic lesions in the aorta of the fetus (maternal dyslipidemia); children with homozygote familial hypercholesterolemia (FH) also have very high levels of lipoproteins in their blood that promote atherosclerosis and can develop symptomatic vascular complications before school age.
However, the paper also points out that due to the influence of genetic variation, some individuals can maintain serum low-density lipoprotein cholesterol (LDL-C) levels below 2 mmol/L (80 mg/dL) throughout their lives, and for these individuals, even if there are many other non-lipid-related risk factors (such as increased blood pressure, obesity, smoking, etc.), ASCVD is almost non-existent.
Which children have the need for long-term lipid lowering?
Although there have not been any long-term interventional studies that directly verify whether the prevention or treatment of cardiovascular risk factors in childhood reduces their risk of future ASCVD. However, data from a large cohort study suggest that atherosclerosis may be completely prevented if levels of apoB-containing lipoproteins in the blood circulation can be controlled within normal physiological ranges through drug interventions (such as statins) from an early age.
Statins have been recommended for the treatment of dyslipidemia in children with FH (treatment from the age of 8), and a growing body of data suggests that this treatment strategy is effective in avoiding atherosclerosis in this high-risk group. So, for other pediatric patients who are not familial dyslipidemia, can we also take such drug treatment regimens for prevention?
The paper points out that because dietary control is too difficult, if LDL-C from childhood to adulthood is to be controlled at a low level as a whole, it is theoretically only possible to achieve it through long-term drug therapy. Although there have been several large clinical trials confirming the safety of statins in pediatric populations. However, given the potential risk of side effects that long-term pharmacotherapy may pose to healthy children, the use of pharmacotherapy strategies is also unrealistic.
Therefore, we may still need dietary and lifestyle interventions to prevent and reduce the impact of cardiovascular disease risk factors in childhood. Even if serum LDL-C is only reduced to a fairly limited level, if it can last for a lifetime, the overall risk of developing ASCVD may be significantly reduced.
However, the paper emphasizes that for other pediatric populations with high risk factors for cardiovascular disease in addition to FH patients, such as transplant recipients, chronic kidney disease or type 1 diabetes, we may still need primary prevention with statins.
Potential future strategies: preventive use in young adults
There is substantial evidence that the earliest possible detection of cardiovascular risk factors or atherosclerosis is essential for the rapid implementation of primary preventive measures.
However, because large-scale long-term use of drug therapy in healthy children may not only have potential health risks, but also accompanied by many ethical issues and widespread opposition, how to better prevent the occurrence of ASCVD in the pediatric population is currently facing difficulties.
▲Vascular changes caused by childhood exposure to high-risk factors (Image source: Reference[1])
The paper pointed out that in addition to familial hypercholesterolemia patients, other pediatric groups are also at higher risk of future cardiovascular events, and how to adopt effective strategies to identify and manage this part of the group urgently requires expert consensus. Strategies for prophylactic use in young adults with atherosclerotic risk factors or preclinical indications (based on non-invasive imaging tests) appear to be more acceptable than in children.
In addition, to date, a number of studies of non-pharmacological intervention strategies have confirmed that lifestyle interventions targeting ASCVD-related risk markers in children can bring some benefits to this group of people, and are expected to promote children's cardiovascular health at the overall population level.
Non-pharmacological interventions will remain an important cornerstone for improving children's cardiovascular health at the overall population level for a long time to come.
Summary
Overall, although multiple studies of non-pharmacological intervention strategies have confirmed that lifestyle interventions based on ASCVD risk markers can provide some degree of benefit to the pediatric population. However, we still need more effective and large-scale eradication strategies to prevent the global pandemic of ASCVD at the population level.
The paper emphasizes that there is an urgent need for consensus on how to effectively identify children at high risk of atherosclerosis, young adults with preclinical risk factors or signs of atherosclerosis, and personalized intervention and management for this group of people.