1.2.4 Lifetime risk for CVD
Age and gender, which are not modifiable, are such powerful determinants of absolute CVD risk over the relatively short 10-year period, that individuals only cross the pre-set threshold of risk (currently 20%) that mandates drug treatment at an older age, despite having important modifiable CVD risk factors from much earlier in life.
In the USA, it has been estimated that up to half of the adult population (predominantly young individuals and women) have a low 10-year CVD risk (<10 b="">but nevertheless have a high risk of a future event (>39%) over their lifetime.1310>
With the current approach to risk stratification, such individuals do not get effective risk factor reduction until late in the evolution of their disease, potentially missing the opportunity to influence favourably CVD evolution.
Recent risk factor guidelines have attempted to overcome this important problem by ‘extrapolating risk from elderly patients back to younger patients’ but these projections are not easy to understand and are subject to many assumptions.14
There is considerable scope for improvement in the communication of CVD risk to patients and the public.
Most surveys suggest that the majority of the public underestimate their lifetime risk of developing and dying of CVD, considering cancer to be a greater threat despite robust evidence to the contrary.
1.2.5 JBS3 lifetime risk approach
A key change in the new JBS3 Guidelines is the adoption of a ‘lifetime risk’ approach to assess and communicate CVD risk, in addition to 10-year absolute risk estimates.
This change is based upon several lines of evidence.
Although most CVD events occur after the age of 50 years,
the atherosclerotic process begins many years earlier,
often from the first decade of life.
Studies have confirmed a steady increase in the presence of atherosclerosis with age in individuals dying from non-cardiac causes.15
Exposure to CVD risk factors occurs from early life and this has been shown to promote the progression of this long preclinical phase of arterial disease.
In large observational trials, levels of classical CVD risk factors in adolescents (including LDL-c, BMI, smoking, and BP) have been associated with increased carotid intima–medial thickness measurements in adulthood, a marker of emerging arterial disease.
The epidemic of obesity and the resulting increase in type 2 diabetes in the young is likely to accelerate disease progression and is predicted to have a substantial adverse impact on the prevalence of CVD in the population over the next 20 years.16
The emergence of CVD appears to be related to long term and cumulative exposure to causal and modifiable risk factors.
The Framingham Heart study examined the relationship between CVD risk profiles at the age of 50 years in men and women and the risk of subsequent CVD events, and showed a large difference in outcomes dependent on risk profiles at this age.17
This emphasised the importance of the interaction between risk factors and the arterial wall in early life, suggesting that prevention efforts need to begin earlier.
The importance of this risk factor exposure for future CVD was confirmed in a meta-analysis of studies which included more than a quarter of a million men and women, and showed a strong influence of CVD risk factors on lifetime risk of CVD.18
This suggests that there is an opportunity to modify the evolution of disease by earlier intervention.
All studies on the impact of CVD risk factors in the young and the potential benefits of early treatments have been observational and use surrogate measures of CVD.
Prospective randomised trials to evaluate the impact of risk factor lowering from a young age on CVD event rates in later life would need to be very long and are not feasible.
Indirect evidence from genetic studies, however, and more direct evidence from intervention trials support the concept that a longer period of cholesterol lowering (and other risk factor lowering) could leverage larger reductions in later CVD risk.
The Atherosclerosis Risk In Communities (ARIC) study reported that a rare genetic variant in the population resulted in lower PCSK9 values (now an important target for drug treatment),
with 28% lowering of lifetime LDL-c concentrations.19
This was associated with an 88% reduction in future CVD events.
More recent work has confirmed that genetic variants which are associated with lower LDL-c values over life are associated with substantially better outcomes than those which can be achieved by equivalent LDL-c lowering with statins in later life.20
FH is perhaps the best example of a monogenic disorder which elevates a causal risk factor, LDL-c, and which results in rapid early manifestations of atherosclerosis and premature CVD morbidity and mortality.
In this context, the concept of statin treatment from a young age to reduce lifetime risk is already universally accepted.
The benefits of early statin use have been shown on progression of carotid intima–media thickness (cIMT), even in prepubertal children.