Is Coronary Calcium a Useful
Additional Risk Factor for Heart Disease?
by David W. Sharp
Many clinicians will label the important papers at #1 and #10
as "wait and see" and look elsewhere in the Top Ten for everyday
guidance. They will find plenty of food for thought but no final
resolution of ongoing controversies. Nor will they see great
variety in journals cited (two-thirds of the top 18 papers were
published in the New England Journal of Medicine) or in
topic. Predictably (as noted in
Science Watch, Jan/Feb 2010) two articles on
prostate cancer screening are gaining ground
(#8 and #9). The management of patients with type 2
diabetes
(Science Watch, May/June 2009) continues to attract
attention (#2, #3, and #5) and there are a couple of outliers to
fuel this long-running debate. At #13 is the Veterans Affairs
study, which found that intensive (versus standard) blood glucose
control had no significant effect on mortality, cardiovascular
events, or microvascular complications (W. Duckworth, et
al., New Engl. J. Med., 360[2]:129-39, 2009; total
cites 115, latest count 38) while in #17 Danish researchers report
that multiple interventions (i.e., not restricted to glucose
control alone) did lead to sustained beneficial effects on
mortality and vascular complications (P. Gaede, et al.,
New Engl. J. Med., 358[6]:580-91, 2008; total cites 219,
latest count 33).
In 2007 an expert committee reintroduced
"obesity," a word that had been avoided in
official discussions of children’s weight (S.E. Barlow,
Pediatrics, 120[suppl]:S164-92, 2007). Without any
shift in the cut-off points, the term "overweight" should, they
said, be replaced by obesity and "at risk of overweight" should
became simply overweight. The cut-offs are, respectively,
body-mass index (BMI) at the 95th percentile for age or more and
BMI in the 85 to 94 percentile range. Sometimes, other
percentiles are used (e.g., 85, 97, and 99), or BMI itself in
kilograms per meter squared is preferred. The prevalence in
young people of severe obesity (BMI at or above the 99th
percentile) tripled in a quarter of a century according to a
U.S. study (J.A. Skelton, et al.,Acad.
Pediatr., 9[5]: 322-9, 2009).This increase is alarming, but
figures from the first half of the 21st century hint at a
levelling-off. A study from the U.S. National Center for Health
Statistics found no significant trend in high BMI over two-year
periods in the time span 1999 to 2006 (C.L. Ogden, et
al., JAMA, 299[10]: 2401-05, 2008; total cites
149, latest count 39, currently ranking #12).
If, when considering the prediction of coronary heart disease, we
need to add to risk factors such as smoking, high blood pressure
and raised cholesterol, coronary-artery calcium (CAC) could be a
candidate (for one review see M.J. Budoff and K.M. Gul, Vasc.
Health Risk Manag., 4[2]: 315-24, 2008). Its measurement is
non-invasive; the technique involves computed tomographic scanning
with radiographic phantoms of known calcium content placed beneath
the patient’s chest. Reviewing no fewer than nine "emerging
risk factors" for the U.S. Preventive Services Task Force, Dr. Mark
Helfand and colleagues set the bar high (Ann. Intern.
Med., 151[7]: 496-507, 2009). A new test should add
significantly to the predictive power of the established, so-called
Framingham, package not only by reclassifying a high proportion of
those labelled as of intermediate risk and but also by leading to
an effective change in clinical management.
The measurement of CAC—unlike that of homocysteine,
C-reactive protein and lipoprotein(a), which are also candidates
and can be studied in blood deep-frozen long ago for other
reasons—cannot be done retrospectively. For CAC, therefore,
the acquisition of good evidence requires much patience. One of the
studies cited in Helfand and colleagues’ review (R. Detrano,
et al., New Engl. J. Med., 358[13]: 1336-45,
2008; total cites 100, latest count 32) currently lies at #18.
These workers found that the cumulative incidence of coronary
events over the years of follow-up was significantly related to the
CAC score. A common statistical technique in predictive studies
such as this is to calculate something called the area under the
receiver-operating-characteristic curve. This allows traditional
risk factors alone to be compared with those same factors with the
new test (CAC) added. There was a significant improvement but it
was small (from 0.79 to 0.83 for major coronary events, the maximum
being 1.00) and as this was not an intervention trial no light is
thrown on the second of Helfand and colleagues’ rightly
demanding criteria.
A former deputy editor of The Lancet, David W.
Sharp, M.A. (Cambridge) is a freelance writer living in
Minchinhamptom, U.K.
Medicine
Top 10 Papers
Rank
Paper
Citations
This Period
(Sep-Oct 09)
Rank
Last Period
(Jul-Aug 09)
1
J. Yu, et al.,
"Induced pluripotent
stem cell
lines derived from human somatic
cells,"Science, 318(5858):
1917-20, 21 December 2007.
[Genome Ctr. Wisconsin, Madison;
U. Wisconsin, Madison] *243HE
81
1
2
The ACCORD Study Group (H.C.
Gerstein, et al.),
"Effects of intensive
glucose lowering in type
2 diabetes,"New
Engl. J. Med., 358(24):
2545-59, 12 June 2008. [Writing
Group: 10 U.S. and Canadian
institutions] *311IJ
72
2
3
The ADVANCE Collaborative Group (A.
Patel, et al.),
"Intensive blood glucose
control and vascular outcomes in
patients with type 2
diabetes,"New Engl.
J. Med., 358(24): 2560-72, 12
June 2008. [Writing Group: 18
institutions worldwide] *311IJ
60
4
4
S.D. Wiviott, et al.,
"Prasugrel versus
clopidogrel in patients with acute
coronary syndromes,"New Engl. J. Med.,
357(20): 2001-15, 15 November 2007.
[8 institutions worldwide] *230RV
53
9
5
R.R. Holman, et al.,
"10-year follow-up of
intensive glucose control in type 2
diabetes,"New Engl.
J. Med., 359(15): 1577-89, 9
October 2008. [6 U.K. institutions]
*358FS
49
6
6
K. Miller, et al.,
"Paclitaxel plus
bevacizumab versus paclitaxel alone
for metastatic
breast
cancer,"New
Engl. J. Med., 357(26):
2666-76, 27 December 2007. [9
U.S. and Canadian institutions]
*245UO
47
†
7
J..M. Llovet, et al.,
"Sorafenib in advanced
hepatocellular carcinoma,"New Engl. J. Med., 359(4):
378-90, 24 July 2008. [22
institutions worldwide] *329FK
44
5
8
F.H. Schroder, et al.,
"Screening and
prostate-cancer
mortality in a randomized
European study,"New Engl. J. Med.,
360(13): 1320-8, 26 March 2009.
[15 institutions worldwide]
*423VP
43
10
9
G.L. Andriole, et al.,
"Mortality results from a
randomized prostate-cancer
screening trial,"New
Engl. J. Med., 360(13):
1310-9, 26 March 2009. [16 North
American institutions] *423VP
43
†
10
I.H. Park, et al.,
"Reprogramming of human
somatic cells to pluripotency with
defined factors,"Nature, 451(7175): 141-6,
10 January 2008. [Harvard Med.
Sch., Boston, MA; Harvard Stem Cell
Inst., Boston, MA] *249GA