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Hypertension. 2008;51:620-621
Published online before print January 22, 2008, doi: 10.1161/HYPERTENSIONAHA.107.100255
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(Hypertension. 2008;51:620.)
© 2008 American Heart Association, Inc.


Editorial Commentaries

Obesity, Insulin Resistance, and Nocturnal Systolic Blood Pressure

Adam Whaley-Connell; James R. Sowers

From the Department of Physiology (J.R.S.), Department of Internal Medicine (A.W-C., J.R.S.), Diabetes and Cardiovascular Center (A.W-C., J.R.S.), University of Missouri School of Medicine, and Harry S. Truman Veterans’ Affairs Medical Center (A.W-C., J.R.S.), Columbia, Mo.

An increasing prevalence of obesity is observed in all age and ethnicity groups and is increasingly being recognized as a serious health problem in children and adolescents.1–4 Obesity is associated with a number of metabolic abnormalities, as well as increased risk for cardiovascular disease (CVD).3,4 In this issue of Hypertension, Lurbe et al5 reported a relationship between insulin resistance, determined by the homeostatic model assessment technique, and nocturnal elevations of systolic blood pressure and heart rate in a large cohort of overweight and obese European children and adolescents. This relationship was present even after adjustment for age, sex, and height. Furthermore, waist circumference was strongly associated with insulin resistance, and both waist circumference and insulin resistance were associated with elevated nocturnal, but not daytime, blood pressures. These are important observations despite some limitations as to the methodology that the investigators used. One limitation of this report is the fact that sleep was not well documented, which limited the ability to strongly relate the nocturnal blood pressures and heart rate to circadian rhythmicity. Another potential limitation of this study relates to the fact that the children were recruited from an obesity clinic; therefore, the data may not be representative of the general population of children and adolescents. Finally, the results of this study are limited by the fact that it was a cross-sectional rather than a prospective longitudinal investigation. Nevertheless, the observations in this study are in concert with previous reports of a positive relationship between insulin resistance and hypertension in children and adolescents.6,7 As noted by the authors, the results of this cross-sectional study need to be validated in prospective longitudinal investigations in this population. Furthermore, the impact of weight reduction and other strategies to improve insulin sensitivity on elevated nocturnal blood pressures would be a potentially important avenue of investigation. Because both nocturnal elevation of blood pressure and insulin resistance are predictive of renal disease,8,9 as well as CVD, the impact of insulin resistance and elevated nocturnal systolic blood pressure in children on blood pressure temporal trends, as well as the impact on development of CVD and renal disease in adulthood, needs to be assessed in future prospective studies.

A loss of the normal 24-hour circadian blood pressure and heart rate pattern has been reported in those with autonomic nervous abnormalities accompanying obesity and insulin resistance.8–11 A nondipping pattern may be promoted by increases in inflammation, oxidative stress, endothelial dysfunction, and early renal disease, as manifested by the presence of microalbuminuria (Figure).8–11 Obesity and insulin resistance contribute to endothelial dysfunction, increased sympathetic nervous system activity, increased cardiovascular and renal oxidative stress, and inflammation (Figure).4 There is increasing evidence suggesting that adipose tissue, especially central fat, is a major source of production of inflammatory cytokines.4 These inflammatory molecules, in turn, may contribute to insulin resistance, endothelial dysfunction, and activation of the sympathetic nervous system, as well as the renin-angiotensin-aldosterone system.12 Collectively, these metabolic and vascular abnormalities are associated with loss of the normal circadian rhythm of blood pressure (Figure).8–11 There are substantial data indicating that the presence of nocturnal nondipping is an important harbinger for CVD and chronic kidney disease in the adult population; the current investigation by Lurbe et al5 highlights the importance of this emerging biomarker for CVD and early renal disease9 in the adolescent population. Therefore, determining its presence and development of strategies to correct this abnormality may be very important in the future management of obesity and insulin resistance in children. This approach could potentially be a preventative measure for the development of CVD and chronic kidney disease in adulthood. Hopefully, publication of this cross-sectional study will lead to prospective studies evaluating the relationship between isolated nocturnal elevations of systolic blood pressure and heart rate and the development of sustained daytime hypertension, as well as biomarkers of CVD and chronic kidney disease during adolescence and early adulthood. Prospective longitudinal studies are also needed to ascertain the impact of weight reduction, exercise, and other hygienic measures in children to determine whether restoration of normal insulin sensitivity and circadian rhythm of blood pressure and heart rate is contemporaneously associated with reductions of albuminuria and other biomarkers of early renal disease and CVD in young adults.


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Figure. Depicts the relationship among nocturnal nondipping, visceral adiposity, and insulin resistance, as mediated by inflammation, oxidative stress, and altered sympathetic nervous system (SNS) output. The presence of nocturnal nondipping is associated with renal (eg, salt retention, microalbuminuria, renin-angiotensin-aldosterone system [RAAS], and chronic kidney disease) and cardiovascular end-organ damage (eg, left ventricular hypertrophy [LVH], ischemic heart disease, and congestive heart failure [CHF]) and increased risk of CVD event.


*    Acknowledgments
 
The authors acknowledge the excellent illustrative support of Stacy Turpin.

Sources of Funding

Funding was provided by the National Institutes of Health and the Department of Veterans Affairs.

Disclosures

The authors have received grants from Novartis and have served as consultants to Novartis, Forrest, and Tahula.


*    Footnotes
 
Correspondence to James R. Sowers, University of Missouri, Columbia School of Medicine, D109 Diabetes Center, UHC, One Hospital Dr, Columbia MO 65212. E-mail sowersj@health.missouri.edu

The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.


*    References
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*References
 
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2. Freedman DS, Dietz WH, Srinivasan SR, Berenson GS. The relation of overweight to cardiovascular risk factors among children and adolescents: the Bogalusa Heart Study. Pediatrics. 1999; 103: 1175–1182.[Abstract/Free Full Text]

3. Lawlor DA, Leon DA. Association of body mass index and obesity measured in early childhood with risk of coronary heart disease and stroke in middle age: Findings from the Aberdeen children of the 1950s prospective cohort study. Circulation. 2005; 111: 1891–1896.[Abstract/Free Full Text]

4. Sowers JR. Obesity as a cardiovascular risk factor. Am J Med. 2003; 115: 37–41.[CrossRef]

5. Lurbe E, Torro I, Aguilar F, Alvarez J, Alcon J, Pascual JM, Redon J. Added impact of obesity and insulin resistance in nocturnal blood pressure evaluation in children and adolescents. Hypertension. 2008; 51: 635–641.[Abstract/Free Full Text]

6. Bao W, Srinivasan SR, Berenson GS. Persistent elevation of plasma insulin levels is associated with increased cardiovascular risk in children and young adults: the Bogalusa Heart Study. Circulation. 1996; 93: 54–59.[Abstract/Free Full Text]

7. Sinaiko AR, Steinberger J, Moran A, Hong CP, Prineas RJ, Jacobs DR Jr. Influence of insulin resistance and body mass index at age 13 on systolic blood pressure, triglycerides, and high-density lipoprotein cholesterol at age 19. Hypertension. 2006; 48: 730–736.[Abstract/Free Full Text]

8. Anan F, Takahashi N, Ooie T, Yufu K, Saikawa T, Yoshimatsu H. Role of insulin resistance in nondipper essential hypertension. Hypertens Res. 2003; 26: 669–676.[CrossRef][Medline] [Order article via Infotrieve]

9. Lurbe E, Redon J, Kesani A, Pascual JM, Tacons J, Alvarez V, Batlle D. Increase in nocturnal blood pressure and progression to microalbuminuria in type 1 diabetes. N Engl J Med. 2002; 347: 797–805.[Abstract/Free Full Text]

10. Sowers JR. Metabolic risk factors and renal disease. Kidney Int. 2007; 71: 719–720.[CrossRef][Medline] [Order article via Infotrieve]

11. Sowers JR, White WB, Pitt B, Whelton A, Simon LS, Winer N, Kivitz A, van Ingen H, Brabant T, Fort JG. The effects of cyclooxygenase-2 inhibitors and non-steroidal anti-inflammatory therapy on 24-hour blood pressure in patients with hypertension, osteoarthritis, and type 2 diabetes mellitus. Arch Intern Med. 2005; 165: 161–168.[Abstract/Free Full Text]

12. Cooper SA, Whaley-Connell A, Habibi J, Wei Y, Lastra G, Manrique C, Stas S, Sowers JR. Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance. Am J Physiol Heart Circ Physiol. 2007; 293: H2009–H2023.[Abstract/Free Full Text]


Related Article:

Added Impact of Obesity and Insulin Resistance in Nocturnal Blood Pressure Elevation in Children and Adolescents
Empar Lurbe, Isabel Torro, Francisco Aguilar, Julio Alvarez, Jose Alcon, Jose Maria Pascual, and Josep Redon
Hypertension 2008 51: 635-641. [Abstract] [Full Text] [PDF]




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