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High mortality explained by mildly elevated blood pressure in Scandinavian adolescent conscripts – A plea for early drug treatment?

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Blood Pressure
Authors:
Sverre Kjeldsen at University of Oslo
Sverre Kjeldsen
Suzanne Oparil at University of Alabama at Birmingham
Suzanne Oparil
Krzysztof Narkiewicz at Medical University of Gdansk
Krzysztof Narkiewicz
Thomas Hedner at University of Gothenburg
Thomas Hedner
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EDITORIAL
High mortality explained by mildly elevated blood pressure in
Scandinavian adolescent conscripts – A plea for early drug treatment?
SVERRE E. KJELDSEN
1 , SUZANNE OPARIL
2 , KRZYSZTOF NARKIEWICZ
3
& THOMAS HEDNER
4
1 Department of Cardiology, Oslo University Hospital, Ullevaal, Oslo Norway,
2 Vascular Biology and Hypertension
Program, University of Alabama, Birmingham, Alabama, USA,
3 Department of Hypertension and Diabetology,
Medical University of Gdansk, Poland and
4 Department of Medicine, University of Göteborg, Sahlgrenska Academy,
Göteborg, Sweden
The Scandinavian countries have for many years
practiced compulsory military service; in this context
all 18-year-old men are subject to an extensive med-
ical examination prior to enlistment. High blood
pressure detected under such conditions is highly
reproducible (1), and markers of stress such as ele-
vated blood pressure, heart rate and plasma cate-
cholamines during mental stress testing are
reproducible many years later in the same population
(2). Such stress markers predict the development of
hypertension (3), weight gain (4) and insulin resis-
tance (5) in middle age, suggesting that these
pathophysiological mechanisms detected in early
adulthood may underlie the development of cardio-
vascular disease later in life.
A large national study of total mortality, cardio-
vascular mortality and non-cardiovascular mortality
in 1.2 million men in Sweden who underwent mili-
tary conscription examinations between 1969 and
1995 at a mean age of 18.4 years and were followed
for a median of 24 (range 0 – 37) years has recently
been reported (6). During follow-up, 28 934 (2.4%)
men died. The relation of systolic blood pressure to
total mortality was U-shaped, with the lowest risk at
a systolic blood pressure of about 130 mmHg. This
pattern was driven by the relation to non-cardiovas-
cular mortality, whereas the relation to cardiovascu-
lar mortality increased monotonically (higher risk
with higher blood pressure). There was also a relation
between diastolic blood pressure and mortality risk,
which in fact was stronger than that of systolic blood
pressure, in terms of both relative risk and popula-
tion attributable fraction (deaths that could be avoided
if blood pressure was in the optimal range). Relations
to cardiovascular and non-cardiovascular mortality
were similar, with an apparent risk threshold at a
diastolic blood pressure of about 90 mmHg. Below
this threshold level, diastolic blood pressure and
mortality were unrelated, and above this level, risk
increased steeply with higher diastolic blood pres-
sures. Approximately 20% of total mortality in these
young men could be explained by their diastolic
blood pressure.
Though limited to men, mostly of Caucasian
origin, these data (6) strongly enforce the idea that
prevention of cardiovascular disease should start in
early adulthood. We have repeatedly called for pro-
spective data from intervention trials carried out in
people with mild hypertension or even high normal
blood pressure, particularly in the young (7,8).
Based on observational data, we recommend that
adolescents should exercise, maintain ideal body
weight, avoid smoking and generally adhere to a
healthy lifestyle. The Swedish conscript data dem-
onstrated that diastolic blood pressure above 90
mmHg in young men is highly predictive of cardio-
vascular and total mortality. Such fi ndings could be
important to support the concept that pharmaco-
logical treatment of blood pressure should be admin-
istered to at risk persons in this younger age group,
even in the absence of data from randomized con-
trolled trials with hard clinical outcomes. This is
particularly important because it is unlikely that ran-
domized outcome data on late adolescents and
young adults will be performed in the near future or
even ever be collected.
In light of exceptionally well tolerated antihyper-
tensive drugs on the market (9), and their generic
low prices and thus cost effectiveness, we may be
moving towards the point that we extrapolate the
positive outcome data from antihypertensive drug
intervention in the middle-aged and elderly to the
Blood Pressure, 2011; 20: 188–189
ISSN 0 803-7051 pri nt/ ISSN 1651-1999 onlin e © 2011 Scandin avia n Foundat ion for Cardiovasc ular R esear ch
DOI : 10. 3109 /0 8037 051.2 011.595 962
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For personal use only.
Editorial 189
young people and support active drug treatment once
blood pressure above certain limits is detected (10,11).
Alternatively or concomitantly, in the world of evi-
denced-based medicine and ethical problems with
extrapolating from the middle-aged and elderly to the
young, we need to investigate the benefi t of drug
treatment of hypertension in the young people by
doing studies with intermediate endpoints, e.g. left
ventricular hypertrophy, vascular remodeling or vas-
cular stiffness, to establish proof of principle that nor-
malization may lead to less cardiovascular endpoints
and reduced blood pressure-related mortality.
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ResearchGate has not been able to resolve any citations for this publication.
Update on the 1987 task force report on high blood pressure in children and adolescents: A working group report from the national high blood pressure education program
Article
Full-text available
  • Oct 1996
Background. The "Report of the Second Task Force on Blood Pressure Control in Children - 1987" developed normative blood pressure (BP) data for children and adolescents. These normative data are used to classify BP levels. Since 1987, additional BP data in children and adolescents, the use of newer classes of drugs, and the role of primary prevention of hypertension have expanded the body of knowledge regarding the classification and treatment of hypertension in the young. Objective. To report new normative BP data in children and adolescents and to provide additional information regarding the diagnosis, treatment, and prevention of hypertension in children. Methods. A working group was appointed by the director of the National Heart, Lung, and Blood Institute as chair of the National High Blood Pressure Education Program (NHBPEP) Coordinating Committee. Data on children from the 1988 through 1991 National Health and Nutrition Examination Survey III and nine additional national data sets were combined to develop normative BP tables. The working group members produced initial draft documents that were reviewed by NHBPEP Coordinating Committee representatives as well as experts in pediatrics, cardiology, and hypertension. This reiterative process occurred for 12 draft documents. The NHBPEP Coordinating Committee discussed the report, and additional comments were received. Differences of opinion were adjudicated by the chair of the working group. The final report was sent to representatives of the 44 organizations on the NHBPEP Coordinating Committee for vote. It was approved unanimously by the NHBPEP Co-ordinating Committee on October 2, 1995. Conclusions. This report provides new normative BP tables for children and adolescents, which now include height percentiles, age, and gender. The fifth Korotkoff sound is now used to define diastolic BP in children and adolescents. New charts have been developed to guide practicing clinicians in antihypertensive drug therapy selection. The primary prevention of hypertension in these age groups is discussed. A statement on public health considerations in the treatment of children and adolescents is provided.
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Association of blood pressure in late adolescence with subsequent mortality: Cohort study of Swedish male conscripts
Article
Full-text available
  • Feb 2011
  • Br Med J
To investigate the nature and magnitude of relations of systolic and diastolic blood pressures in late adolescence to mortality. Nationwide cohort study. General community in Sweden. Swedish men (n = 1,207,141) who had military conscription examinations between 1969 and 1995 at a mean age of 18.4 years, followed up for a median of 24 (range 0-37) years. Total mortality, cardiovascular mortality, and non-cardiovascular mortality. During follow-up, 28,934 (2.4%) men died. The relation of systolic blood pressure to total mortality was U shaped, with the lowest risk at a systolic blood pressure of about 130 mm Hg. This pattern was driven by the relation to non-cardiovascular mortality, whereas the relation to cardiovascular mortality was monotonically increasing (higher risk with higher blood pressure). The relation of diastolic blood pressure to mortality risk was monotonically increasing and stronger than that of systolic blood pressure, in terms of both relative risk and population attributable fraction (deaths that could be avoided if blood pressure was in the optimal range). Relations to cardiovascular and non-cardiovascular mortality were similar, with an apparent risk threshold at a diastolic blood pressure of about 90 mm Hg, below which diastolic blood pressure and mortality were unrelated, and above which risk increased steeply with higher diastolic blood pressures. In adolescent men, the relation of diastolic blood pressure to mortality was more consistent than that of systolic blood pressure. Considering current efforts for earlier detection and prevention of risk, these observations emphasise the risk associated with high diastolic blood pressure in young adulthood.
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Management of high blood pressure in children and adolescents: Recommendations of the European Society of Hypertension
Article
  • Jul 2010
Hypertension in children and adolescents has been gaining ground in cardiovascular medicine, mainly due to the advances made in several areas of pathophysiological and clinical research. These guidelines arose from the consensus reached by specialists in the detection and control of hypertension in children and adolescents. Furthermore, these guidelines are a compendium of scientific data and the extensive clinical experience it contains represents the most complete information that doctors, nurses and families should take into account when making decisions. These guidelines, which stress the importance of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, should act as a stimulus for governments to develop a global effort for the early detection and suitable treatment of high pressure in children and adolescents. J Hypertens 27:1719-1742 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins. 2010 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.
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Long-Term Stability of Cardiovascular and Catecholamine Responses to Stress Tests An 18-Year Follow-Up Study
Article
  • Nov 2009
  • Hypertension
Cardiovascular (CV) hyperreactivity to stress must be reasonably stable if it is considered to be important in the development of hypertension and CV disease. The aim of the present study was to assess long-term stability of blood pressure, heart rate, epinephrine, and norepinephrine responses to a cold pressor test and a mental arithmetic stress test. Eighty-one subjects selected from the first (n=30), 50th (n=30), and 95th to 99th (n=39) percentiles of the mean blood pressure distribution at a military draft procedure were tested on 2 occasions 18 years apart. Stress responses were measured during a cold pressor test (hand immersed in ice water for 1 minute) and during a mental stress test (subtraction for 5 minutes). Intra-arterial blood pressure measurements and arterial catecholamine samples were taken at the initial examination. At follow-up, noninvasive Finapres beat-to-beat blood pressure measurements and venous plasma catecholamine samples were used. The 18-year correlations of the CV and epinephrine absolute responses during mental stress ranged from 0.6 to 0.8. The entry/follow-up correlation of systolic blood pressure during the mental stress test (95% CI: 0.69 to 0.86) was significantly higher than during the cold pressor test (95% CI: 0.30 to 0.65), and responses to mental stress overall appeared to be more stable than responses to the cold pressor test. Our study suggests that CV and sympathoadrenal reactivity, specifically to mental stress, are relatively stable individual characteristics. These results support one of the necessary preconditions to consider hyperreactivity involved in the development of hypertension and CV disease.
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Management of high blood pressure in children and adolescents: Recommendations of the European Society of Hypertension
Article
  • Aug 2009
Hypertension in children and adolescents has gained ground in cardiovascular medicine, thanks to the progress made in several areas of pathophysiological and clinical research. These guidelines represent a consensus among specialists involved in the detection and control of high blood pressure in children and adolescents. The guidelines synthesize a considerable amount of scientific data and clinical experience and represent best clinical wisdom upon which physicians, nurses and families should base their decisions. They call attention to the burden of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers, to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.
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Increased sympathetic reactivity may predict insulin resistance: an 18-year follow-up study
Article
  • Nov 2008
Insulin resistance and sympathetic activity are related by a positive feedback system. However, which precedes the other still remains unclear. The present study aimed to investigate the predictive role of sympathoadrenal activity in the development of insulin resistance in an 18-year follow-up study. We also examined whether reactivity to 2 different stress tests, a cold pressor test and a mental stress test, would differ in their predictive power. The 2 tests are supposed to represent different reactivity mechanisms: alpha- and beta-adrenergic responses, respectively. At entry, arterial plasma epinephrine and norepinephrine concentrations were measured in 99 healthy men (age, 19.3 +/- 0.4 years, mean +/- SD) during rest, a mental stress test, and a cold pressor test. Fasting plasma glucose concentration was measured at entry and at follow-up. Insulin resistance at follow-up was calculated using the homeostasis model assessment of insulin resistance (HOMA-IR). Eighty subjects (81%) were eligible for follow-up after 18.0 +/- 0.9 years (mean +/- SD). The norepinephrine responses to cold pressor test at entry predicted plasma glucose concentration (r = 0.301, P = .010) and HOMA-IR (r = 0.383, P = .004) at follow-up in univariate analyses. In multiple regression analyses, corrected for fasting glucose at entry, family history of diabetes, blood pressure-lowering medication, body mass index at entry, and level of exercise, norepinephrine response to cold pressor test was found to be a positive predictor of future HOMA-IR (P = .010). This is the first long-term follow-up study in white subjects showing that sympathetic reactivity predicts future insulin resistance 18 years later. These findings may provide further insights into the pathophysiologic mechanisms of insulin resistance.
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Cardiovascular reactivity, coronary risk factors, and sympathetic activity in young men
Article
  • Jan 1994
We have previously demonstrated that awareness of high blood pressure may increase blood pressure, plasma catecholamine levels, and stress responses. In the present study, three groups of 19-year-old men, all unaware of their blood pressure status, were selected from the first (group-1, 62 +/- 2 mm Hg, [mean +/- SEM], n = 15), 50th (group-50, 90 +/- 4 mm Hg, n = 15), and 99th (group-99, 123 +/- 5 mm Hg, n = 14) percentiles in causal mean blood pressure at a screening. They were studied (blinded examiners) with intra-arterial blood pressure recordings and multiple measurements of arterial plasma epinephrine and norepinephrine during a mental arithmetic challenge and cold pressor test. Despite high mean blood pressure at the screening, group-99 did not differ from group-50 either in intra-arterial mean blood pressure after 30 minutes of supine rest (89 +/- 3 versus 86 +/- 2 mm Hg) or in serum lipids and resting plasma epinephrine and norepinephrine. However, in group-99 resting plasma epinephrine showed a positive hyperbolic relation to resting diastolic blood pressure (r = .73, P = .004) and a negative hyperbolic relation to the ratio of high-density lipoprotein cholesterol to total cholesterol (r = -.75, P = .002). None of these correlations were present in the two other groups. Furthermore, the three groups differed in heart rate responses (P < .0005) and systolic (P < .0005) and diastolic (P < .05) blood pressure responses to mental arithmetic challenge, group-99 being hyperreactive compared with the other two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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