Should cholesterol lowering medication be started in the young?

Earlier treatment of elevated cholesterol results, even for children when indicated, results in better outcomes

While the general perception is that strokes only occur in the elderly, over the years, there has been a gradual increase in the prevalence of strokes in the young. Recently, a young patient of mine, who is in his 20s with multiple risk factors for heart disease and stroke, was found to have near complete occlusion of one of his major arteries in the brain, the middle cerebral artery (MCA). The MCA provides blood supply to the part of the brain that controls power, sensation and speech. A stroke involving this artery will not only result in severe disability but can also be life threatening.

Stroke in the young

Severe narrowing of an artery within the skull is termed as intracranial stenosis and encompasses narrowing of the brain arteries. Intracranial stenosis is a common cause of stroke and is particularly prevalent in Asians. In a 2017 study on young Chinese with intracranial stenosis published in the Annals of Translational Research, it was found that in about 80 per cent of those with unilateral blockage of the MCA, the underlying cause was attributable to atherosclerosis. Atherosclerosis is the condition where there is narrowing of the arterial wall (plaque formation) due to the build-up of fat, cholesterol, calcium, and other substances found in the arterial wall. While atherosclerosis remains the main cause of blockage of brain arteries in the young, there are also other causes such as vessel malformation (Moyamoya disease), inflammation of vessels (vasculitis), abnormal arterial wall growth (fibromuscular dysplasia), tear of the artery (arterial dissection); however, these are more prevalent in young females.

Earlier studies showed that for those with significant intracranial stenosis, there was about a one-in-eight chance of getting a stroke or even death within a one- to two-year period even with medical treatment. A more recent publication on the Oxford Vascular Study in May 2020 in Lancet Neurology demonstrated that the risk of intracranial stenosis stroke for those on intensive medical therapy was lower when compared to previous studies, being 5.6 per cent one-year risk (compared to 9.4 per cent in VISSIT, a study on treatment of intracranial stenosis) and 5.6 per cent two-year risk (compared to 14.1 per cent in SAMMPRIS, a study on treatment of intracranial stenosis). The better outcomes in the Oxford Vascular Study may be explained by better medical treatment available in more recent years. In the Chinese Intracranial Atherosclerosis (CICAS) Study, the highest rate of recurrent stroke was seen in those with three or more risk factors.

The major risk factors include high cholesterol level, diabetes mellitus, smoking and high blood pressure. Hence, optimal control of risk factors is essential in those with intracranial stenosis.

Atherosclerosis in children and young adults

While it may come as a surprise to many that the young can develop significant blockage of arteries, the data proving that atherosclerosis is prevalent in the young has been around for some time. Autopsy data from young men with a mean age of 22 years who died during the Korean war showed that more than 70 per cent of them had atherosclerosis in their heart arteries. A similar study on young Americans who perished in the Vietnam war showed that 45 per cent had atherosclerosis and 5 per cent had severe heart artery atherosclerosis. Studies on younger cohorts showed evidence of early onset atherosclerosis in children. A study of young American motor accident victims showed that more than 50 per cent of children aged 10 to 14 years have evidence of early atherosclerosis. In the Bogalusa Heart Study, early atherosclerosis (presence of fatty streaks in the heart arteries) was present in about 50 per cent of those aged from two to 15 years.

Never too young for prevention

Cholesterol remains the single most important risk factor for stroke and heart disease. While it is almost unthinkable in the past to consider starting children on cholesterol-lowering drugs (statins), there is now almost universal agreement that in those with familial hypercholesterolaemia (genetically high cholesterol levels), treatment should commence at a young age. The European Atherosclerosis Society (EAS) consensus panel and the latest American College of Cardiology-American Heart Association (ACC-AHA) guidelines for familial hypercholesterolemia recommend that statins be commenced from as young as eight years (EAS) to 10 years (ACC-AHA) of age. In October 2019, the New England Journal of Medicine published a 20-year follow-up study of children with familial hypercholesterolemia who were started on statin medication at an age of eight to 18 years.

Their results were compared with their affected parents with familial hypercholesterolemia who were only given statins much later in their lives. At the end of the follow-up period, 99 per cent of young patients receiving statins had cardiovascular disease-free survival compared to 74 per cent for their affected parents. This meant that earlier commencement of statin therapy in these at-risk young patients resulted in better long-term outcomes. The latest consensus from the EAS and the International Society of Atherosclerosis (ISA) is that it is not a hypothesis but a fact that LDL cholesterol (“bad” cholesterol) is a major determinant of atherosclerosis. The development of atherosclerosis in arteries is not just dependent on the absolute LDL cholesterol level but also by the cumulative exposure of the arterial wall to LDL cholesterol.

Hence, preventing the development of atherosclerosis not only embodies the concept of “the lower the better” with respect to the LDL cholesterol level, but also a newer concept that “the younger the better”, meaning earlier treatment of elevated cholesterol results in better outcomes.

Early detection

While prevention remains the cornerstone of management, there will be invariably some at-risk young people who may get a stroke. Understanding the symptoms is a key step in early detection and management. Patients with significant intracranial stenosis can present with symptoms of a transient insufficiency in blood flow to the brain (transient ischemic attack) or a stroke. While symptoms such as weakness of one side of the body, slurring of speech, and numbness of one side of the body are easily recognised as an evolving stroke, other symptoms such as severe headache, changes in vision and severe dizziness or a spinning sensation (vertigo) are less well recognised as symptoms of stroke. While ultrasound of the neck (carotid) arteries is commonly used to assess the risk of stroke, it has its limitations. In the CICAS Study, only 20 per cent of those with intracranial stenosis had co-existing neck carotid artery disease, which means that the absence of disease in the neck carotid arteries does not mean that there is no significant intracranial stenosis.

For patients with symptoms, an MRI of the brain and brain arteries can provide confirmation. In an acute stroke, a CT scan of the neck and brain arteries is usually performed at the Emergency Department to help the doctor make a decision on therapeutic choices. In summary, evolving lifestyle and dietary changes have resulted in the development of atherosclerosis in children and young adults. Elevated LDL cholesterol remains the key driver of atherosclerosis and early management, even for children when indicated, can lead to better cardiovascular disease-free outcomes.

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