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Prehypertension during Young Adulthood and Coronary Calcium Later in Life

Mark J. Pletcher, MD, MPH; Kirsten Bibbins-Domingo, PhD, MD; Cora E. Lewis, MD; Gina S. Wei, MD, MPH; Steve Sidney, MD, MPH; J. Jeffrey Carr, MD, MSCE; Eric Vittinghoff, PhD; Charles E. McCulloch, PhD; and Stephen B. Hulley, MD, MPH
[+] Article, Author, and Disclosure Information

From the University of California, San Francisco, and San Francisco General Hospital, San Francisco, California; University of Alabama at Birmingham, Birmingham, Alabama; National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland; Kaiser Permanente, Oakland, California; and Wake Forest University, Winston-Salem, North Carolina.

Acknowledgment: The CARDIA Study is supported by contracts N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, and N01-HC-95095 from the National Heart, Lung, and Blood Institute.

Potential Financial Conflicts of Interest: None disclosed.

Reproducible Research Statement:Study protocol: Available at http://www.cardia.dopm.uab.edu. Statistical code: Available from Dr. Pletcher (e-mail, mpletcher@epi.ucsf.edu). Data set: A limited-access data set is available at http://www.nhlbi.nih.gov/resources/deca/descriptions/cardia.htm.

Requests for Single Reprints: Mark J. Pletcher, MD, MPH, 185 Berry Street, Suite 5700, San Francisco, CA 94107.

Current Author Addresses: Drs. Pletcher, Vittinghoff, McCulloch, and Hulley: 185 Berry Street, Suite 5700, San Francisco, CA 94107.

Dr. Bibbins-Domingo: San Francisco General Hospital Building 10, Box 1364, WD 13 1313, University of California, San Francisco, San Francisco, CA 94143-1364.

Dr. Lewis: 1717 11th Avenue South, Suite 614, Birmingham, AL 35205.

Dr. Wei: 6701 Rockledge Drive, Suite 10018, Bethesda, MD 20892-7936.

Dr. Sidney: 2000 Broadway, Oakland, CA 94612.

Dr. Carr: 2000 West 1st Street, Two Piedmont Plaza, Suite 618, Winston-Salem, NC 27104-4225.

Author Contributions: Conception and design: M.J. Pletcher, K. Bibbins-Domingo, J.J. Carr, S.B. Hulley.

Analysis and interpretation of the data: M.J. Pletcher, G.S. Wei, J.J. Carr, E. Vittinghoff, C.E. McCulloch.

Drafting of the article: M.J. Pletcher, S.B. Hulley.

Critical revision of the article for important intellectual content: M.J. Pletcher, K. Bibbins-Domingo, C.E. Lewis, G.S. Wei, J.J. Carr, E. Vittinghoff, C.E. McCulloch, S.B. Hulley.

Final approval of the article: M.J. Pletcher, K. Bibbins-Domingo, C.E. Lewis, G.S. Wei, J.J. Carr, E. Vittinghoff, C.E. McCulloch, S.B. Hulley.

Provision of study material: C.E. Lewis, J.J. Carr, S.B. Hulley.

Statistical expertise: M.J. Pletcher, E. Vittinghoff, C.E. McCulloch.

Obtaining of funding: C.E. Lewis.

Administrative, technical, or logistic support: C.E. Lewis, G.S. Wei.

Collection and assembly of data: C.E. Lewis, J.J. Carr, S.B. Hulley.

Ann Intern Med. 2008;149(2):91-99. doi:10.7326/0003-4819-149-2-200807150-00005
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Of 5115 CARDIA participants enrolled in 1985 to 1986, 3549 attended the 20-year examination, and 3138 had cardiac computed tomography at that time. An additional 558 participants who had cardiac computed tomography only at year 15 were also eligible. Of these 3696 participants, we excluded 136 who had hypertension before age 35 years, which left 3560 participants in the study sample. Blood pressure measurements were missing at 1 or more examinations for 842 (24%) participants, but mixed modeling yielded trajectory estimates for all 3560 participants (see Methods section). About one half of participants were black (46%), about one half were women (56%), and the average age was 44 years at the time of the index cardiac computed tomography. Coronary calcium was present in 17% of participants, and calcium scores were mostly low; only 3% of participants had extensive calcification (defined as a calcium score >100).

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Figure 1.
Coronary calcium score distribution in middle age with increasing exposure to systolic prehypertension before age 35 years.

Cumulative exposure to systolic prehypertension is measured by calculating the area under the systolic blood pressure trajectory in mm Hg–years (analogous to pack-years of tobacco exposure). The association with the coronary calcium score category is significant (P < 0.001). Values inside the bars are the numbers of participants (percentages of group total). Ten persons with a positive coronary calcium scan but an unknown coronary calcium score were excluded from this analysis.

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Appendix Figure.
Example of an estimated systolic blood pressure trajectory.

The trajectory slope is allowed to change at age 30 and 40 years. Shading shows how the area under the blood pressure trajectory is partitioned by age to yield the primary predictor (cumulative exposure to blood pressure elevation before age 35 years). Cumulative exposure before age 35 years occurs only in the prehypertension range in our sample, because persons with hypertension before age 35 years were excluded.

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Submit a Comment/Letter
The rise and rise of "prehypertension"
Posted on July 22, 2008
Tom Marshall
University of Birmingham
Conflict of Interest: None Declared
A quick search of Medline reveals that prehypertension was rarely used before 2003. The term was largely invented by JNC VII. From 2004 forwards there are many papers that mention it. What exactly does this word mean and why is it so persistent? It means blood pressure within or slightly above the normal range. In other words it is a way of categorising what is a continuous variable (blood pressure). Why does it persist? Prehypertension sounds like an illness. It sounds like a necessary precursor to hypertension, part of a slippery slope. In this respect it resembles terms like "premalignant". But it is not really the same as premaliganant, because even hypertension is simply a way of categorising a continuous variable. There is no magic threshold of blood pressure that is free from risk of vascular disease. We have known this for decades. Higher blood pressure measns higher incidence of vascular disease. Higher is a relative term. Persons whose usual blood pressure is 115/70 mm Hg are at lower risk of vascular disease than those whose usual blood pressure is 120/75 mm Hg and so on. We also know that blood pressure tends to rise with age. Those with higher blood pressures when young are likely to end up with higher blood pressures when old. So what are we being told here? People with higher blood pressures than average are at higher risk of vascular disease than average - we have known this since the first Framingham study was published decades ago. Why does this half-baked term persist? First because it sounds like an illness it is a gift to marketers of hypotensive drugs. Indeed the TROPHY study made drew the absurd conclusion that we could prevent hypertension (a condition effectively defined as eligibility for drug treatment) by starting drug treatment. Another reason is that in the US there is great attachment to using categorical variables to define eligiblity for hypotensive treatment whereas in much of the rest of the world (led by New Zealand) eligibility for treatment is determined by calculating predicted incidence of cardiovascular disease as a continuous variable. Is this just failure of imagination in the USA? Ironically, New Zealand guidelines use the US Framingham equation to predict risk, whereas in the USA it is rarely used. The answer may be more prosaic. Most primary care physicians in the USA do not have electronic medical records. Whereas in New Zealand, Australia, UK, Netherlands and Scandinavia it is almost unheard of for a primary care physician to lack electronic medical records. And electronic medical records make Framingham risk calculations simple. So while the rest of the world moves towards an understanding of CVD risk that is based on predicted incidence of illness, in the USA there are simply attempts to expand the categorical variable that encompasses those defined as eligible for treatment. Conflict of Interest:

None declared

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Summary for Patients

High-Normal Blood Pressure in Young Adults as a Risk for Atherosclerosis Later in Life

The summary below is from the full report titled “Prehypertension during Young Adulthood and Coronary Calcium Later in Life.” It is in the 15 July 2008 issue of Annals of Internal Medicine (volume 149, pages 91-99). The authors are M.J. Pletcher, K. Bibbins-Domingo, C.E. Lewis, G.S. Wei, S. Sidney, J.J. Carr, E. Vittinghoff, C.E. McCulloch, and S.B. Hulley.


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