hypertension in teens predicts future heart disease

 A recent article assessed the long-term effects of hypertension on subsequent cardiovascular events (see htn adolescent inc CAD risk AnnIntMed2023 in dropbox, or doi:10.7326/M23-0112)

 

Details:

-- 1,366,519 males in late adolescence who were conscripted into the military in Sweden from 1969 to 1997, in an observational cohort study (>48 million person-years at risk)

-- analysis was based on the ACC/AHA 2017 guidelines classifying blood pressure elevation:

    -- normal blood pressure: <120/<80 mmHg (238,041 individuals)

    -- elevated blood pressure: 120-129/<80 mmHg (393,196 individuals)

    -- stage I isolated systolic hypertension ( ISH): 130-139/<80 (346,791 individuals)

    -- stage I isolated diastolic hypertension (IDH) : <130/80-89 (59,279 individuals)

    -- stage I systolic – diastolic hypertension (SDH): 130-139/80-89 (66,103 individuals)

    -- stage II ISH: >140/<90 (246,161 individuals)

    -- stage II IDH: <140/>90 (7306 individuals)

    -- stage II SDH: >140/>90 (8742 individuals)

 

-- mean age 18

-- baseline blood pressure:

    -- normal: <120/80 mmHg): 17.5%

    -- elevated (120-129/<80 mmHg): 28.8%

    -- hypertensive (>130/80 mmHg): 53.7%

 

-- over these eight subgroups of hypertension: proteinuria, and the comorbidities of diabetes, alcoholism, renal disease, and cardiovascular disease, were pretty evenly divided across the hypertension subgroups (though very low numbers of each at baseline)

-- mean income decile was also very similar across the groups, as was marriage status

-- however, education level did vary by blood pressure group: those with less than high school degree had a trend towards increase from 13.7% to 21.7% as a blood pressure got worse, those with high school degree decreased from 52% to 45%, and those with college degree or higher had similar distribution of around 32%

 

-- Primary outcome: a composite of cardiovascular death or first hospitalization for MI, heart failure, ischemic stroke, or intracerebral hemorrhage

-- Median follow-up 35.9 years

 

Results:

-- the results below were fully adjusted for BMI, height, exercise capacity, proteinuria, diabetes, renal disease, cardiovascular disease (excluding hypertension), alcoholism, income decile, education level and marriage  status

-- primary outcome (composite), 79,644 participants, as compared to those with normal blood pressure (reference group):

    -- elevated blood pressure: 10% increased risk, adjusted HR 1.10 (1.07-1.13)

    -- stage I isolated systolic hypertension (ISH:) 15% increased, aHR 1.15 (1.11-1.18)

    -- stage I isolated diastolic hypertension (IDH): 23% increased, aHR 1.23 (1.18-1.28)

    -- stage I both systolic/diastolic hypertension (SDH): 32% increased risk, aHR 1.32 (1.27-1.37)

    -- stage II ISH: 31% increased risk, aHR 1.31 (1.28-1.35)

    -- stage II IDH: 55% increased risk, aHR 1.55 (1.42-1.69)

    -- stage II SDH: 71% increased risk, aHR 1.71 (1.58-1.84

 

-- The cumulative risk for cardiovascular events increased gradually across blood pressure stages ranging from 14.7% for normal blood pressure to 24.3% for stage II SDH at age 68 years

 Commentary:

-- the prevalence of hypertension has increased in children and adolescents over time, where isolated systolic hypertension (ISH) is the  predominant form

-- hypertension is the leading cause of cardiovascular disease and premature death in the world

 

-- this study found that with up to 50 years of followup, there was a quite substantial increase in cardiovascular events in adulthood when the adolescent BP was high, and this increase tracked with the severity of the blood pressure in adolescence, including both the systolic and diastolic blood pressures individually and especially combined

    -- effectively, one in 10 adolescents with stage 2 systolic/diastolic hypertension would have a major cardiovascular event at age 68 vs those with normal adolescent blood pressure readings

-- one implication of this study is that there seems to be a cumulative risk of cardiovascular events over time: for hypertension, the process of atherosclerotic disease is, no so surprisingly, a progressive one that starts early and progresses over the years (for more information on this cumulative process, see https://gmodestmedblogs.blogspot.com/2023/10/update-ascvd-risk-factor-critique.html )

    -- and this suggests that we clinicians should be treating hypertension in adolescents aggressively, as with hyperlipidemia in adolescents, which really translates largely to strongly supporting non-pharmacologic strategies in terms of diet (eg low salt DASH diet), exercise, developing/maintaining a normal weight, decreasing stress….  And, this is pretty difficult, requiring lots of hand-holding with patients, seeing them pretty frequently to help reinforce changes, and best using motivational interviewing techniques

    -- also, given the large size of the sample in this study, they were able to show not just a decrease in cardiovascular events in the composite, but also for each of the individual components

    -- it is also important to underscore that isolated systolic hypertension is important and should not be dismissed as being a result of the highly elastic arteries of youth (which amplifies the systolic pressure on their contraction; some studies have found that the elevated arm systolic blood pressure in some individuals can be associated with normal blood pressure centrally and presumably innocent: this study suggests that in general we should consider ISH as a real cardiac risk factor)

-- another study found that the duration of hypertension was a cardiovascular risk factor independent of the recorded level of the blood pressure (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9618611/ )

-- and another found that blood pressure variability was an independent cardiovascular risk factor: https://gmodestmedblogs.blogspot.com/2016/09/blood-pressure-variability-increases.html

-- this all supports the concept that hypertension is associated with cardiovascular disease in a complex manner (and not one covered in our ASCVD risk calculators: the cardiovascular risk is associated with hypertension whenever it seems to be measured (especially with assessments through ambulatory blood pressure monitoring or home monitoring), but is independently associated with the duration of hypertension (ie, we clinicians should inquire about this) as well as blood pressure variability (which suggests we should use medications that decrease blood pressure variability, such as amlodipine, chlortalidone, ARBs (losartan at full dose of 100mg or any of the other ARBs at any dose) 

 

-- Although no women were involved in this study, an analysis based on a combination of the Framingham Heart Study, Multi-Ethnic Study of Atherosclerosis, Atherosclerosis Risk in Communities Study, and the Coronary Artery Development in Young Adults Study found that women had increased MIs and heart failure at a lower threshold of SBP than men (Sex Differences in Blood Pressure Associations With Cardiovascular Outcomes | Circulation (ahajournals.org) ); this was reaffirmed in a scientific statement on sex differences in arterial hypertension by a cohort of European cardiovascular societies: https://academic.oup.com/eurheartj/article/43/46/4777/6711154

 

Limitations:

-- there is no information about their methodology of assessing blood pressure, or the consistency of how it was assessed, although we do know that the BP was measurd in the supine position and likely in stressful conditions of military recruitment (ie, not “ideal”), and was measured only once, decades before the measured cardiovascular outcomes (and things may change over time….)

-- statistics about social economic variables in Sweden were assessed in this cohort beginning at age 40, so this very important information is not so clear for younger people

    -- from the methodology in the article and the supplementary material, it does not seem that the researchers tracked hypertension, comorbidities, diet, exercise, weight, smoking, lipids, stressors/social parameters, alcohol, diabetes, medications taken as people aged (this database was created as a national database and not for research purposes)

-- the individuals studied were all conscriptable men, limiting generalizability to women as well as to the 2-3% of men who were disabled and not conscriptable

-- this study included an ethnically and racially homogeneous population, which might also limit the generalizability of the conclusions

-- the outcomes of the study were not centrally adjudicated (though the inpatient register has been validated for their cardiovascular findings)

 

So, this study does add a few important perspectives:

-- hypertension in teens tracks with increased cardiovascular events as older adults, making it an important marker that needs to be addressed, non-pharmacologically (preferably), but with meds as needed

-- diastolic hypertension in this study of teens was at least as predictive of future cardiovascular events. In adults, systolic hypertension seems to be the worst: https://journals.lww.com/co-nephrolhypertens/abstract/2003/05000/what_is_the_most_important_component_of_blood.11.aspx

-- there is a real complexity as to how hypertension should be incorporated into our cardiovascular risk assessment:

    -- both systolic and diastolic hypertension play a role

    -- the duration of hypertension is an independent risk factor, and patients with longer duration should be considered to have higher cardiovascular risk

    -- the variability of hypertension matters: we should probably be preferentially prescribing meds that have a 24-hour duration of action and less variability over that 24 hours

    -- and we should consider these complexities when we treat hypertension, a disease with a cumulative progression to future cardiovascular events (for more evidence/information, see https://gmodestmedblogs.blogspot.com/2023/10/update-ascvd-risk-factor-critique.html)

 

geoff

-----------------------------------

If you would like to be on the regular email list for upcoming blogs, please contact me at gmodest@bidmc.harvard.edu

  

to get access to all of the blogs:

 

 go to http://gmodestmedblogs.blogspot.com/ to see the blogs in reverse chronological order

  -- click on 3 parallel lines top left, if you want to see blogs by category, then click on "labels" and choose a category​

  -- or you can just click on the magnifying glass on top right, then type in a name in the search box and get all the blogs with that name in them

 

if you would like to see the articles in this blog, please email me. 

 

please feel free to circulate this to others. also, if you send me their emails (gmodest@bidmc.harvard.edu), i can add them to the list