By Dr. Geoffrey Modest
The USPSTF just came out with their lipid screening recommendations for children and adolescents (see JAMA 2016; 316(6): 625), giving them an “I” rating (current evidence insufficient to recommend screening). For full supporting documents of the USPSTF recommendations, see JAMA 2016; 316(6): 645). Their points:
- They consider both dyslipidemia from genetic heterozygous familial hypercholesterolemia, FH, (1 in 200-500 people in North America and Europe), where there are really high cholesterol levels (LDL>190 mg/dl, often 2-3x that of unaffected people) and evidence of increased cardiovascular risk (though not typically until age 30: 1 in 6 men and 1 in 10 women have ischemic heart disease by age 40, 25% of women and 50% of men by age 50), as well as multifactorial dyslipidemia, MD, (may have genetic component as well as environmental, esp obesity, where the LDL is lower but >130). Several studies show that there is moderately good tracking of childhood hyperlipidemia into adulthood. But they comment that there are no long-term data that adolescent hyperlipidemia from MD leads to clinical cardiac events in adults. Or that treatment of the MD changes those hard clinical outcomes [i.e., no RCTs have been done, and it is hard to imagine that they ever will be. Would require lots of kids randomized into different treatment wings, maintaining those treatments for decades, and then being able to follow them until they were 50+ years old when more clinical events happen]
- NHANES data suggest that 7.8% of children 8-17 yo have total cholesterol >200 mg/dl, and 7.4% of those 12-19 have LDL >130 [i.e., pretty common]
- For those with FH there are data that short-term (<2 year) treatment leads to decreased LDL and decreases the early surrogate marker of carotid intima-media thickness [which actually seems to be a good predictor of future atherosclerotic disease, especially in kids]. There are no compelling data on the long-term benefit of statins through a randomized-controlled trial, since in those with FH it is considered unethical not to use statins. However, a retrospective analysis looked at children with FH who were put on statins for a mean of 10 years starting at age of 14, and compared them to the adults with FH not on statins (they predated the use of statins); they assessed outcomes by age 30 , finding that the adults had many more cardiovascular events at a younger age than the kids (at the age of 30, the cumulative CVD survival was about 90%, vs 100% in the kids, even though 28% of the kids were smokers. See Braamskamp MJ. Am J Coll Cardiol 2016; 67(4): 455). It was notable in this study that the youngest parent with an MI was 20 years old and died at age 23.
- Harms of screening. Also inadequate evidence, though mostly concerns about medicalization (anxiety about diagnosis, labeling, potentially harmful therapy). Statins are well tolerated with transient adverse effects in kids (increased liver enzymes). And though cardiovascular disease is still the number one killer, there is concern about overdiagnosis (i.e., some people treated may never develop cardiovascular disease)
- Therapy: statins are typically used, given the adult data. But no consensus on when to start in kids with FH (some say age 8-10, some age 20). No data on long-term use in kids [though there are potential issues concerning taking statins with pregnancy, which they did not mention….]
- They do acknowledge the rationale for screening kids:
- Atherosclerosis is a known progressive process which starts in kids, with autopsy studies showing that [my data, not in their document]:
- Everyone has fatty streaks in their coronaries by age 15-34
- Advanced atherosclerotic lesions are found in 2% of men and 0% of women aged 15-19, but
- Advanced atherosclerotic lesions are found in 20% of men and 8% of women aged 30-34
- The Bogalusa Heart Study found that in adolescents dying mostly from trauma at median age of 19.6, there was a strong correlation between the levels of cardiovascular risk factors (BMI, lipids, and BP) and the degree of atherosclerosis
- Lipid levels in kids are associated with the extent of adult atherosclerosis
- Familial hypercholesterolemia, FH, is associated with premature ischemic cardiovascular disease
- Short-term treatment of patients with FH leads to substantially lower LDL levels and some evidence of improvement in atherosclerosis (see below)
- Abnormal lipid levels in adults is strongly associated with coronary heart disease events
- Early identification and intervention in adults can prevent such events
- And, I would add, prevention of more advanced lesions upfront not only decreases mortality (still a significant number of patients die with their first MI, and more are chronically disabled), but also helps long-term, since statins do not reverse atherosclerosis (just stabilizes it and makes the plaques less likely to rupture), but the residual recurrent cardiac risk in those who sustain an MI (secondary prevention) even with statins remains much higher than in those on statins who are just at elevated cardiovascular risk (i.e., primary prevention)
- Although there are some potential benefits of identifying and treating those with FH, there are no good data for those with multifactorial dyslipidemia. An Ohio universal screen program (n=6500) looked at nonfasting total cholesterol screening, finding elevated levels >200 in 8.5%. This cohort then had fasting lipids, finding 5.8% had LDL>130. The USPSTF review found that those with the highest likely yield for hyperlipidemia are kids with obesity (12.3%), overweight (8.9%), children 9-11yo (7.2%) and those 16-19 yo (7.2%) [There is an unexplained typical 10-15% decrease in cholesterol levels during puberty].
- When reading guidelines, it is important to remember that USPSTF overall is an independent governmental agency (so less influenced by drug companies, etc., than some of the professional society recommendations), is very focused on rigorous data (so will not make recommendations if the issue has not been studied well. They say the same thing about blood pressure screening in kids: no data that screening leads to decreased future cardiovascular events, so an “I” rating). In fact, for pretty much the same reasons (lack of clearcut studies), USPSTF does not recommend screening average risk males until age 35 and women till 45. All of these USPSTF recommendations are much less aggressive than the Am Acad of Pediatrics (screen at age 2-10 in all obese kids or if family history of dyslipidemia, etc.), NCEP (screen at age 20), Am College of Physicians, etc.
- And, as a perspective, we all screen for phenylketonuria in newborns, with a prevalence of 1 in 10,000, but not for familial hypercholesterolemia, with 50x the prevalence (>500,000 born each year)… though I do realize the rigor of studies showing benefit is different)
- It is pretty clear that targeted screening of those considered to be high risk is not successful: in a few pediatric epidemiologic studies, 1/2 the kids would be missed by relying on parental information/ family history of dyslipidemia or premature cardiovascular disease (e.g., see Ritchie SK. Pediatrics 2010; 126(2):260). And, pretty surprisingly, only about 1/4 of FH patients receive their appropriate diagnosis by middle age (see Neil HA. BMJ 2000; 3212:148). From other organizations (e.g. Am Acad of Pediatrics), screening has been recommended as universal. Universal screening is also much easier to integrate into care than targeted screening.
- I do definitely think that discussing diet and exercise is really important at all age groups (though adolescents may be the most resistant of them….). But I also do think, from my clinical experience, that this discussion is more effective, at least in some people, if there are personal specific markers that suggest that the individual may be at higher risk. And knowing the lipid levels of adolescents may be very helpful in changing behavior. For example, I think that knowing a person smokes helps individualize their treatment recommendations and is likely to be more effective than just telling everyone they should not smoke (of course, finding out that someone smokes is a bit less invasive than doing a blood test).
- So, to me, the rationale to do testing wins out. One may pick up the relatively unusual cases of familial hypercholesterolemia, and it seems pretty intuitive that they need meds as supported by our understanding of their physiology and supplemented by some limited data. But one will mostly pick up the pretty common multifactorial hyperlipidemia, and I personally would pursue these patients aggressively with diet and exercise, based on logic but without definitive studies to prove it. I.e., I would use the found high lipid levels to talk with the patient (motivational interviewing) about diet and exercise and suggest much more aggressive follow-up than on their non-dyslipidemic peers. I would not start meds in this group, but if they were able to improve their lifestyle, would track their lipids and give them feedback. And, it turns out that most adolescents do not have optimal lifestyles (see next study)
Not so surprisingly to those in clinical practice with kids/adolescents, there are very impressive data that adolescents have pretty bad lifestyles in terms of cardiovascular health. A recent AHA scientific statement (see DOI: 10.1161/CIR.0000000000000441) noted:
- 91% had poor diets, 9% intermediate diets: specifically, overconsumption of sodium, sugar, solid fats, refinded carbohydrates; under consumption of fruits, vegetables, whole grains, dairy, dietary fiber
- Only 10% of boys and 5% of girls aged 16-19 years old had the recommended 60 minutes of moderate-to-vigorous exercise per day (including muscle-strengthening and bone-loading activities at least 3 days/week. [By the way, my untested hypothesis is that kids can use their cellphones, which seem to be pretty ubiquitous even in poorer communities, to track their “numbers of steps” they take each day, in order both to quantify an important aspect of exercise and give direct feedback to them]
- 27% of12-19 year olds are obese (BMI>95th percentile)
- This document does promote “early identification and control of dyslipidemia, including heterozygous familial hypercholesterolemia, throughout youth and into adulthood can reduce clinical cardiovascular disease risk beginning in young adult life”. Also it is typical that total cholesterol decreases 10-15% around puberty, independent of diet (suggesting that we should check lipids when kids are 9-11 yo, before these pubertal changes). Non-HDL is more predictive than any single lipid marker. NHANES data suggest that 26-35% of adolescents have “intermediate or poor” levels of total cholesterol overall (worst in Mexican-Americans, best in non-Hispanic whites)
- Blood pressure. Use sex/height-specific percentile charts. 9-12% have intermediate or poor BP status
- Fasting glucose <100 mg/dL. Part of the AHA’s Strategic Impact Goal Through 2020 and Beyond, though they note that this metric is not currently used in pediatric practice, misses the boat in obese children since hyperinsulinemia is the first sign of metabolic derangement, and does not adhere to the Am Diabetes Assn definitions (which are the same as for adults). By the fasting blood glucose <100 metric, 20-38% of 12-19 year olds have intermediate or poor levels in the NHANES study.
- Smoking (twice as common in adolescents exposed to second-hand smoke: reinforcing the need to get parents/caregivers not to smoke, at least in the house). NHANES data suggest that about 1/3 of 12-19 year olds have tried cigarettes within the prior 30 days.
So, this all reinforces the approach of lipid screening in adolescents, despite the lack of clinical outcome data. To me, the reasons to screen younger people are not just to pick up the extreme cases of familial hypercholesterolemia (which typically requires meds) but to use the results as a concrete means to educate adolescents/families about the need for lifestyle changes, with a focus on diet, exercise and obesity, for anyone with hyperlipidemia.
A Response to: USPSTF Does Not Back Lipid Screening in Adolecents
See the response below, sent around with Holly’s permission. Her study (hyperlink below) in 3 sets of adolescents/young adults aged 17-21 and their parents (including some with familial hypercholesterolemia, obesity, and generally healthy) posited different cholesterol screening scenarios, finding that in each of these 3 groups, both the adolescents and the parents saw worse cholesterol results as signifying poorer health, with several commenting about the need to change their lifestyles. This provides support for universal cholesterol screening and using the results to try to influence behavior. Even in adolescents.
Awesome summary Geoff about an issue near and dear to my heart (pun intended!).
I am interested in whether knowing about heart health/heart disease risk changes teens behavior. Probably not but certainly gives us something to anchor our counseling on as you note. You might find this qualitative study we did asking teens about their hypothetical response to lipid screening interesting – http://www.jahonline.org/article/S1054-139X(16)00106-3/fulltext
Thanks as always for such an awesome blog!!!
Holly Gooding, MD, MSc
Division of Adolescent/Young Adult Medicine, Boston Children’s Hospital
Division of General Internal Medicine, Brigham and Women’s Hospital
Harvard Medical School, Boston, MA