Advance Access Publication 7 February 2007
Juice Powder Concentrate and Systemic Blood Pressure,Progression of Coronary Artery Calcium and AntioxidantStatus in Hypertensive Subjects: A Pilot Study
M. C. Houston1, B. Cooil2, B. J. Olafsson3 and P. Raggi4
1Hypertension Institute of Nashville, Vanderbilt University School of Medicine and Saint Thomas Hospital,2Owen Graduate School of Management, Vanderbilt University, 3The Heart Group, Saint Thomas HeartInstitute and Saint Thomas Hospital, Nashville, TN and 4Department of Medicine and Division of Cardiology,Emory University School of Medicine, Atlanta, Georgia, USA
Because micronutrients from plants may have beneficial cardiovascular effects, the hypothesisthat an encapsulated juice powder concentrate might affect several measures of vascular healthwas tested in free living adults at low cardiovascular risk. Blood pressure, vascular compliance,lipid and antioxidant markers, and serial electron beam tomography (to calculate a coronaryartery calcium score as a measure of atherosclerosis burden), were monitored in 51 pre-hypertensive and hypertensive subjects over 2 years. By the end of follow-up, systolicand
(1.9 Æ 0.6 ml mmHgÀ1 Â 100, P50.01). The progression of coronary artery calcium score wassmaller than expected compared with a historical database (P50.001). Laboratory testingshowed a significant decrease in homocysteine (P ¼ 0.05), HDL cholesterol (P ¼ 0.025) and ApoA (P ¼ 0.004), as well as a significant increase in b-carotene, folate, Co-Q10 and a-tocopherol(all P50.001). The phytonutrient concentrate we utilized induced several favorable modifica-tions of markers of vascular health in the subjects. This study supports the notion that plantnutrients are important components of a heart healthy diet.
Keywords: antioxidant – blood pressure – coronary artery calcium – fruit – hypertension –vegetable
advantages, supportive laboratory and epidemiological
The protective effects of fruits and vegetables against
evidence, randomized clinical trials of selected antiox-
coronary heart disease and myocardial infarction have
idant vitamins (A, C, E) and selenium have produced
been reported in numerous populations worldwide (1–5).
conflicting results related to coronary heart disease and
In observational studies, antioxidant vitamins, associated
cardiovascular disease (9–15). Of interest, some cultures
with an increased dietary intake of fruits and vegetables,
rely heavily on the effect of herbal medicines for control
have been inversely associated with cardiovascular disease
of hyperlipidemia, hypertension and other ailments (16).
Science Advisory Council and the American College ofCardiology
antioxidant vitamin supplements for cardiovascular pre-
For reprints and all correspondence: Paolo Raggi, MD, 1365 Clifton
vention; nonetheless, these organizations do recommend
Road NE, AT-504, Atlanta, Georgia 30322, USA. Tel: (404) 778-5567;Fax: (404) 778-3540; E-mail: [email protected]
the consumption of a diet high in sources of antioxidants
ß 2007 The Author(s)This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work isproperly cited.
Phytonutrient effects on vascular markers
and other nutrients such as fruits, vegetables, whole
Imaging, Vascular Compliance, Blood Pressure
grains and nuts to reduce the risk of cardiovascular
All patients underwent imaging with electron beam
This prospective pilot study was undertaken to evaluate
tomography 3 times: at baseline, 12 and 24 months
the effect of a proprietary encapsulated juice powder
(though these time points were not tightly monitored and
concentrate, made primarily of multiple fruits, vegetables
some patients underwent the repeat scans at slightly
and berries on several surrogate markers of cardio-
different times but no more than a week or two from the
vascular health and risk in asymptomatic adults. Assessed
planned time). All electron beam tomography scans were
were: progression of coronary artery calcium score,
a sensitive marker of atherosclerosis; systemic and
San Francisco, CA, USA) according to a standardized
diastolic blood pressure; arterial compliance; markers
protocol. In brief: 40 to 50 tomographic sections with
of antioxidant status and serum lipid levels in patients
a single slice thickness of 3 mm were obtained during a
taking the phytonutrient preparation for 2 years.
single breath holding period. Scanning was electrocardio-graphically triggered at 60–80% of the R–R interval onthe surface electrocardiogram and imaging began at the
level of the bronchial carina and extended to the level ofthe diaphragm. All areas of calcification with a minimal
computed tomography attenuation of 130 HounsfieldUnits seen within the borders of the coronary arteries
This 24-month prospective pilot study was approved by
were computed. A calcified plaque was considered
the local Institutional Review Board. Informed consent
present if at least three contiguous pixels with a density
was obtained from 54 ambulatory patients (44 men)
of 130 Hounsfield Units or greater were detected.
between the ages of 40 and 75 years asymptomatic for
All images were reviewed on a NetraMD workstation
coronary heart disease. Subjects were recruited from the
Hypertension Institute and the Saint Thomas Medical
Scans were considered of acceptable research quality
Group practices in Nashville, TN, USA. All subjects were
only if the images were free from motion or metal
asymptomatic for coronary heart disease (no clinical
artifacts. All scans were read blindly by one (BJO)
experienced investigator for consistency. A coronary
revascularization) and had a coronary artery calcium
artery calcium score for each area of interest was
score at enrollment between 30 and 400. The lower
calculated as originally described by Agatston et al. (20).
coronary artery calcium score threshold was chosen
This scoring method incorporates the density and volume
based on published evidence demonstrating better repro-
of a calcified plaque, therefore a score increase may be due
ducibility beyond this limit (19). A coronary artery
to either plaque enlargement or increased density or both.
calcium score 4400 has been shown to be associated
The reverse would be true for a score decrease. Total
with a high risk of obstructive coronary artery disease
calcium scores were calculated as the sum of all individual
and cardiac events and it was therefore decided a priori to
coronary artery scores. The published median inter-scan
exclude such high risk patients. Further inclusion criteria
coronary artery calcium score variability for the Agatston
included baseline fasting LDL cholesterol 54.92 mmol lÀ1
score is 8–10% (21). The total radiation dose absorbed by
and triglycerides 54.52 mmol lÀ1, and two or fewer risk
each patient from the three scans was of $1.5 mSievert
factors for coronary heart disease. Exclusion criteria
(the maximum recommended yearly dose is 5 mSv for
included symptomatic angina or known coronary heart
disease, single vessel coronary artery stenosis over 50%
or left main artery stenosis over 30%. Additional
utilized for assessment of arterial wave forms and small
therapy, concomitant use of any antioxidant, vitamin,
vessel as well as large vessel arterial compliance.
nutritional or nutraceutical supplements and women of
Compliance is measured as the change in vessel diameter
After enrollment, no changes were allowed in anti-
(ml /mmHgÀ1 Â 100). Arterial compliance was measured
hypertensive medications, other prescription drugs or
aspirin during the study period. No dietary or activity
Baseline history, physical exam, blood pressure, weight,
asked to maintain their habitual diet, exercise program,
4 months for 24 months. Blood pressure was recorded
tobacco utilization, alcohol intake and other lifestyle
as the average of two manual measurements and
three automated measurements, taken after the subject
lay in a supine position for 15 min. Laboratory tests for
b-carotene, a-tocopherol, folate, Co-Q10, vitamin C,
the study due to prescription of an excluded medication.
glycated hemoglobin and a lipid profile were performed
These six subjects are included in the data until the time
by a commercial diagnostic laboratory (Kronos Science
of their withdrawal. Hence, comparisons were made only
Laboratories, Inc., Phoenix, AZ, USA). Blood samples
between patients who had baseline assessments and
were collected at baseline, 4 months and 24 months.
remained in the study at each analysis point.
Annualized change and relative annualized change were
calculated for each patient at 1- and 2-year intervals forblood pressure values, weight, arterial compliance values,
Subjects were instructed to take three capsules of the
coronary artery calcium score values (absolute scores
and percentiles) and blood chemistries. Coronary artery
Compliance with study protocol was determined by
calcium score percentiles were calculated as the proportion
review of patient diaries and investigators’ pill count at
of patients with coronary calcium in predefined and
each visit, and averaged 85% or better during the follow-
non-overriding age groups from a database of 10 122
up period. The phytonutrient preparation (Juice PlusþÕ,
asymptomatic patients (22). The annualized rates of
NSA, Inc., Memphis,TN, USA) is an encapsulated juice
absolute change and relative change in coronary artery
powder concentrate blend consisting primarily of fruits,
calcium score were compared to changes recorded in
vegetables and berries including: acerola cherry, apple,
historical untreated controls of 29.7 and 34.7%, respec-
beet, bilberry, blackberry, black currant, blueberry,
tively, (23) using one-sample t-tests. In general, changes
broccoli, cabbage, carrot, cranberry, Concord grape,
were annualized for primarily two reasons: patients did not
elderberry, kale, orange, papaya, parsley, peach, pine-
return for follow-up visits at precise 12-month intervals,
apple, raspberry, red currant, spinach and tomato.
and annualization facilitates the comparison between
Six capsules daily provided $7.5 mg b-carotene, 276 mg
changes at intervals of 12 and 24 months (Table 1).
and about 63 kJ. Other than minor gastrointestinal
coronary artery calcium score values because comparative
complaints early in the study, there were no reports of
historical data were only available in annualized format.
adverse effects attributed to the phytonutrient prepara-
In each case, the paired t-statistic was used to construct
tion over the 24 months of follow-up.
confidence intervals and to test for significant annualizedchanges between baseline and follow-up among all
patients first and pre-hypertensive and hypertensive
Of the 54 subjects entering the investigation, three with-
patients later. The one-sample Wilcoxon test on medians
drew before the first follow-up visit. One woman withdrew
was used to confirm significance in this case. Welch’s
due to the prescription of a medication excluded from the
t-test was used to compare all baseline values of pre-
study and two men due to gastrointestinal distress possibly
hypertensive and hypertensive patients, and significant
due to the phytonutrient preparation. The remaining
results were confirmed using the Mann–Whitney rank
51 subjects contributed data. One man withdrew consent
sum test. Best-subsets regression was used to study how
after the 4-month follow-up visit, one man withdrew
age, sex, hypertension, and baseline body weight, arterial
consent after the 8-month follow-up visit, three subjects
compliance values and coronary calcium measures were
(one woman, two men) withdrew consent after the
related to the annualized changes over 2 years in systemic
12-month follow-up visit and one man withdrew from
blood pressure, arterial compliance and coronary calcium
Table 1. Annualized changes at 12- and 24-month follow-up for coronary artery calcium scores, arterial compliance, and blood pressure, with valuesexpressed as mean Æ SEM (median, range)
Small artery compliance (ml mmHgÀ1 Â 100)
Large artery compliance (ml mmHgÀ1 Â 100)
*P50.05; **P50.01; ***P50.001 (relative to baseline) by paired t-test (and Wilcoxon one-sample test).
aCalcium score comparisons with historical 29.7-point annual change: these are significant relative to annualized 24-month change for full cohort(P50.001), 24-month change for pre-hypertensives (P50.01) and 24-month change for hypertensives (P50.05); it is not significantly different fromthe 12-month change in the full cohort.
Phytonutrient effects on vascular markers
measurements. The best models were chosen as those that
61 Æ 6.5 years. Table 1 shows the mean annualized
minimized the Bayesian Information Criterion (BIC)
changes (measured change divided by number of months
subject to the constraint that the ratio of observations
of observation and multiplied by 12) at 12 and 24 months of
to parameters exceeded 5, but this ratio actually exceeded
follow-up for coronary artery calcium scores, arterial
10 for all selected models. The BIC has been shown
compliance and blood pressure. The annualized change
to be a consistent criterion in very general theoretical
in absolute coronary artery calcium score was 26 Æ 6 points
settings and to provide models that perform well in
at 12 months (P50.001 from baseline) and 17 Æ 3.2 points
at 24 months (P50.001 from baseline). These valuescorresponded to a relative change of 26 Æ 6 and 20 Æ 4%,
respectively from baseline (P50.001 in each case). In comparison, the annualized change in absolute and
Baseline Characteristics and Change in Coronary Artery
relative coronary artery calcium score in historical
untreated controls were 29.7 and 34.7%, respectively (23)(P50.001 for each, one-sample t-tests).
enrolled in the study are shown in Table 2. Most of the
Change in Arterial Blood Pressure and Compliance
Figure 1 shows the change over time in systolic blood
The majority were men (80%) and the mean age was
pressure and Fig. 2 shows the change over time in
Table 2. Baseline clinical characteristics
Mean Æ SD (median, range) Mean Æ SD (median, range) Mean Æ SD (median, range)
Small artery compliance (ml mmHgÀ1 Â 100)
Large artery compliance (ml mmHgÀ1 Â 100)
Glycosylated hemoglobin, proportion of total hemoglobin 0.055 Æ 0.008 (0.056, 0.050)
Values expressed as percentages, mean Æ SD, and median and range where appropriate. The P-values refer to comparisons between pre-hypertensive and hypertensive patients: *P50.05; **P50.01; ***P50.001 by Welch’s t-test(and Mann–Whitney rank sum test).
diastolic blood pressure from baseline, at each of the six
decrease in homocysteine (P50.05), HDL cholesterol
follow-up visits. Both measures decreased significantly
(P ¼ 0.025) and Apo A (P ¼ 0.004). Additionally, a
in the full cohort at the end of 2 years of follow-up
significant increase was seen in b-carotene, folate,
Co-Q10 and a-tocopherol (all P50.001). Finally, glyco-
P50.05 and diastolic À2.2 Æ 0.6 mmHg, P50.001) in
sylated hemoglobin showed a borderline significant
the absence of any modification in anti-hypertensive
decrease (P ¼ 0.059), and LDL cholesterol a borderline
therapy. Large artery compliance improved significantly
(1.9 Æ 0.6 ml mmHgÀ1 Â 100, P50.01), while small arterycompliance showed a slight but non-significant decrease.
Table 4 summarizes the best models for all significant2-year changes (Table 1) in systemic blood pressure,
Table 3 shows that compared with baseline, at the end
arterial compliance and coronary calcium measurements.
of 24 months of follow-up there was a significant
The baseline values of these variables, along with age,sex, and baseline weight, were considered as candidate
predictors. Hypertension is significant in models for both
change and relative change in calcium score, and baselinesystolic blood pressure is the pre-eminent predictor in
both models for change in systemic blood pressure.
Our main findings could be summarized as follows: the
mean calcium score changes at the end of follow-up in
this group were statistically smaller than the changesrecorded in an historical population (29.7 and 34.7%,
0 4 8 12 16 20 24 0 4 8 12 16 20 24 0 4 8 12 16 20 24
respectively, P50.001 in each case). In addition, these
pilot study subjects also had reduced systemic bloodpressure in the presence of stable anti-hypertensive
Figure 1. Systolic blood pressure change over time, shown by full
therapy and improved vascular compliance of large
cohort and the hypertensive and pre-hypertensive subgroups, with eachbox plot showing the distribution of subject values for recorded systolic
arteries in the absence of change in body weight (data
blood pressure measured at baseline and 4-month intervals for six
not shown). The above changes were concurrent with an
follow-up visits. The means of each distribution are connected across
improvement in markers of antioxidant status, homo-
cysteine and glycosylated hemoglobin.
These data may provide a rationale for the observed
reduced incidence of coronary heart disease in vegetar-
ians, who demonstrate a 3–5 year overall longer survival
compared to omnivores. The European Prospective
Investigation into Cancer and Nutrition-Oxford studyof 56 000 British men and women demonstrated areduced risk for coronary heart disease in vegetarians
(24). In several observational studies components of aplant-based diet, such as phytochemicals (25), fiber (26),
nuts (27) and whole grain cereals (28), have been
shown to reduce the risk for coronary heart disease.
Furthermore, vegetarian diets, coupled with intense lifestyle changes, have resulted in angiographic improvement
of obstructive coronary artery disease (29). Multiple
0 4 8 12 16 20 24 0 4 8 12 16 20 24 0 4 8 12 16 20 24
studies have suggested that an optimal intake of fruits,
vegetables, whole grains and fiber may provide a
Figure 2. Diastolic blood pressure change over time, shown by full
variety of cardio-protective nutrients and non-nutrient
cohort and the hypertensive and pre-hypertensive subgroups, with each
factors with improvement in endothelial function, blood
box plot showing the distribution of subject values for recorded
pressure, serum lipid levels, glucose, homocysteine,
diastolic blood pressure measured at baseline and 4-month intervals forsix follow-up visits. The means of each distribution are connected
weight, body fat and reduction in oxidative stress and
vascular inflammation (30–34). It has been suggested
Phytonutrient effects on vascular markers
Table 3. Baseline and annualized 24-month change in lipids and other blood values expressed as mean Æ SD
Glycosylated hemoglobin, proportion of total hemoglobin
Table 4. Best models for variables of Table 1 that changed significantly over 24 months in terms of baseline values (for all Table 1 variables, alongwith sex, weight, and hypertension)
Dependent (R-square) 24-month annualized change in:
aWhen a constant is added to this model its coefficient is larger than its standard error. In each case, the direction of univariate association is thesame as the sign of multivariate coefficient.
that a plausible explanation for such favorable effects
could be particularly helpful in patients at intermediate
may be a nutrient–gene interaction that contributes to
risk of events (36) where the presence of calcium increases
a reduction in coronary heart disease.
(and its absence decreases) the probability of an event.
Coronary artery calcification is an excellent marker
In this light, a middle-aged man with hypertension
of atherosclerosis and its presence is associated with
(as most of the patients in our study) may benefit from
a substantially increased risk of cardiac events (35–38).
calcium screening for more accurate risk stratification.
Some investigators have suggested modifying the calcu-
Recently, sequential coronary artery calcium scoring has
lated Framingham Risk Score with data derived from
been used to monitor the progression of atherosclerosis in
calcium screening, thereby increasing or decreasing the
adults treated with lipid-lowering agents (38), phosphate
estimated risk of an event (39,40). Calcium screening
binding agents in renal failure (41) as well as nutritional
supplements (42). Of note, progression of coronary
used to assess arterial compliance (42), others have
artery calcium score has been shown to be associated
disputed this opinion and finding the CR-2000 highly
with a significant increase in risk of cardiovascular events
(23,38). Hence, slowing of coronary artery calcium
In summary, this pilot study showed a favorable effect
score progression appears to be a worthy goal of therapy.
of an encapsulated juice powder concentrate, made
Importantly, the best predictor of coronary artery
primarily of multiple fruits, vegetables and berries, on
calcium score progression in this study was hypertension,
several surrogate markers of cardiovascular disease.
suggesting the very significant role played by this risk
Additional placebo-controlled prospective studies will be
factor in progression of atherosclerosis.
Abnormal arterial compliance, an accurate marker of
vascular stiffness, has been shown to be associated withaging, multiple cardiovascular risk factors and with an
adverse cardiovascular outcome (43). Improvement in
This work was supported in part by the Dean’s Fund
arterial compliance in this pilot study is further evidence
Management, Vanderbilt University, Nashville, TN and
vegetables on the overall vascular health of an individual.
by a grant from NSA, Inc., Memphis, TN, USA.
While the importance of antioxidants in the reduction
of cardiovascular disease remains controversial, theparallel reduction of oxidative stress and other markers
of vascular damage are reassuring. In this light, it is
1. Hirvonen T, Pietinen P, Virtanen M, Ovaskainen ML, Hakkinen S,
intriguing that a powder concentrate containing numer-
Albanes D, et al. Intake of flavonols and flavones and riskof coronary heart disease in male smokers. Epidemiology 2001;
ous phytonutrients, as opposed to tablets of single
vitamins, was sufficient to attain the favorable surrogate
2. Hertog MG, Feskens EJ, Hollman PC, Katan MB, Kromhout D.
Dietary antioxidant flavonoids and risk of coronary heart disease:The Zutphen Elderly Study. Lancet 1993;342:1007–11.
We have no biologically plausible explanation for Juice
3. Sasazuki S, Fukuoka Heart Study Group. Case-control study of
Plusþ alone (in the absence of a change in weight as
nonfatal myocardial infarction in relation to selected foods in
discussed earlier) to have any impact on cholesterol
Japanese men and women. Jpn Circ J 2001;65:200–6.
4. Law MR, Morris JK. By how much does fruit and vegetable
lipoprotein concentrations. Juice Plusþ has been shown
consumption reduce the risk of ischaemic heart disease? Eur J Clin
to impact LDL cholesterol oxidation, but not total
amount of LDL cholesterol and no effect on HDL has
5. Joshipura KJ, Hu FB, Manson JE, Stampfer MJ, Rimm EB,
Speizer FE, et al. The effect of fruit and vegetable intake on risk for
ever been demonstrated. Even though a diet high in
coronary heart disease. Ann Intern Med 2001;134:1106–14.
fruits, vegetables and whole grains is beneficial regarding
6. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA,
lipoprotein concentrations, this effect is largely attributed
Willett WC. Vitamin E consumption and the risk of coronary heartdisease in men. N Engl J Med 1993;328:1450–6.
to the fiber components of these foods. When cholesterol
7. Stampfer MJ, Hennekens CH, Manson JE, Colditz GA, Rosner B,
was monitored more closely, as in the study by Plotnick
Willett WC. Vitamin E consumption and the risk of coronary heart
et al. (44), no consistent effect was noted. In observa-
disease in women. N Engl J Med 1993;328:1444–9.
8. Salonen RM, Nyyssonen K, Kaikkonen J, Porkkala-Sarataho E,
tional studies a reduction, and not an increase, in LDL
Voutilainen S, Rissanen TH, et al. Six year effect of combined
cholesterol has been associated with lack of progression
vitamin C and E supplementation on atherosclerotic progression:
of coronary artery calcium (45), while there has been no
the Antioxidant Supplementation in Atherosclerosis Prevention(ASAP) study. Circulation 2003;107:947–53.
study so far of the effect of HDL level modification on
9. Stephens NG, Parsons A, Schofield PM, Kelly F, Cheeseman K,
coronary calcium. Hence, one would have expected a
Mitchinson MJ. Randomised controlled trial of vitamin E in
negative effect on calcium progression from the observed
patients with coronary disease: Cambridge Heart Antioxidant Study(CHAOS). Lancet 1996;347:781–6.
changes in cholesterol lipoprotein but this did not occur.
10. Boaz M, Smetana S, Weinstein T, Matas Z, Gafter U, Iaina A,
To further investigate this issue, we searched the human
et al. Secondary prevention with antioxidants of cardiovascular
medical literature for evidence that b-carotene or vitamin
disease in end-stage renal disease (SPACE): Randomised placebo-controlled trial. Lancet 2000;356:1213–8.
E may impact lipid concentrations, but found no
11. GISSI-Prevenzione Investigators. Dietary supplementation with n-3
polyunsaturated fatty acids and vitamin E after myocardial
Limitations of this pilot study included the small
infarction: Results of the GISSI-Prevenzione trial. Lancet 1999;354:447–55.
sample size and lack of a placebo group. The comparison
12. Yusuf S, Dagenais G, Pogue J, Bosch J, Sleight P. Vitamin E
of change in coronary artery calcium score compared
supplementation and cardiovascular events in high-risk patients.
to the historical database is not optimal because of
The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med 2000;342:154–60.
temporal differences of when that data were collected,
13. Heart Protection Study Collaborative Group. MRC/BHF Heart
along with other potential differences between this
Protection Study of antioxidant vitamin supplementation in 20,536
study population and the contributors to the database
high-risk individuals: a randomised placebo-controlled trial. Lancet2002;360:23–33, doi:10.1016/S0140-6736(02)09328-5.
information. In addition, although some investigators
14. Hodis HN, Mack WJ, LaBree L, Mahrer PR, Sevanian A, Liu CR,
have raised concerns about the reliability of the CR-2000
et al. Alpha-tocopherol supplementation in healthy individuals
Phytonutrient effects on vascular markers
reduces low-density lipoprotein oxidation but not atherosclerosis:
hypercholesterolemic adults: a randomized trial. Ann Intern Med
31. Dragsted LO, Pedersen A, Hermetter A, Basu S, Hansen M,
15. Rapola JM, Virtamo J, Ripatti S, Huttunen JK, Albanes D,
Haren GR, et al. The 6-a-day study: Effects of fruit and vegetables
Taylor PR, et al. Randomised trial of alpha-tocopherol and beta-
on markers of oxidative stress and antioxidative defense in healthy
carotene supplements on incidence of major coronary events in men
nonsmokers. Am J Clin Nutr 2004;79:1060–72.
with previous myocardial infarction. Lancet 1997;349:1715–20.
32. Gao X, Bermudez OI, Tucker KL. Plasma C-reactive protein and
16. Azaizeh H, Saad B, Khalil K, Said O. The state of the art of
homocysteine concentrations are related to frequent fruit and
traditional Arab herbal medicine in the Eastern region of the
vegetable intake in Hispanic and non-Hispanic white elders.
Mediterranean: A review. Evid Based Complement Alternat Med
33. Ros E, Nunez I, Perez-Heras A, Serra M, Gilabert R, Casals E,
17. Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC,
et al. A walnut diet improves endothelial function in hypercholes-
Douglas JS, et al. ACC/AHA 2002 guideline update for the
management of patients with chronic stable angina – summary
article: a report of the American College of Cardiology/American
34. Lopez-Garcia E, Schulze MB, Manson JE, Meigs JB, Albert CM,
Heart Association Task Force on Practice Guidelines (Committee
Rifai N, et al. Consumption of (n-3) fatty acids is related to plasma
on the Management of Patients with Chronic Stable Angina).
biomarkers of inflammation and endothelial activation in women.
18. Mosca L, Appel LJ, Benjamin EJ, Berra K, Chandra-Strobos N,
35. Raggi P, James G. Coronary calcium screening and coronary risk
Fabunmi RP, et al. Evidence-based guidelines for cardiovascular
stratification. Curr Atheroscler Rep 2004;6:107–11.
disease prevention in women. Circulation 2004;109:672–93.
36. Pletcher MJ, Tice JA, Pignone M, Browner WS. Using the coronary
19. Callister TQ, Cooil B, Raya SP, Lippolis NJ, Russo DJ, Raggi P.
artery calcium score to predict coronary heart disease events:
Coronary artery disease: improved reproducibility of calcium
a systemic review and meta-analysis. Arch Intern Med 2004;
scoring with an electron-beam CT volumetric method. Radiology
37. Greenland P, LaBree L, Azen SP, Doherty TM, Detrano RC.
Coronary artery calcium score combined with Framingham score
Viamonte M Jr, Detrano R. Quantification of coronary artery
for risk prediction in asymptomatic individuals. JAMA 2004;
calcium using ultrafast computed tomography. J Am Coll Cardiol
38. Raggi P, Cooil B, Ratti C, Callister TQ, Budoff M. Progression of
coronary artery calcium and occurrence of myocardial infarction
Muschiol G, Groth J, et al. Variability of repeated coronary
in patients with and without diabetes mellitus. Hypertension 2005;
artery calcium measurements by electron beam tomography. Am J
39. Grundy SM. Cholesterol management in the era of managed care.
22. Raggi P, Callister TQ, Cooil B, He ZX, Lippolis NJ, Russo DJ,
et al. Identification of patients at increased risk of first unheralded
acute myocardial infarction by electron-beam computed tomogra-
factor in the modified Framingham risk score. BMC Med Imaging
23. Raggi P, Cooil B, Shaw LJ, Aboulhson J, Takasu J, Budoff M,
41. Chertow GM, Burke SK, Raggi P. Treat to Goal Working
et al. Progression of coronary calcium on serial electron beam
tomographic scanning is greater in patients with future myocardial
and aortic calcification in hemodialysis patients. Kidney Int
infarction. Am J Cardiol 2003;92:827–9.
24. Key TJ, Appleby PN, Davey GK, Allen NE, Spencer EA,
Travis RC. Mortality in British vegetarians: review and preliminary
results from EPIC-Oxford. Am J Clin Nutr 2003;78:533S–8S.
ented by ultrafast computed tomography. J Appl Nutr 1996;
25. Most MM. Estimated phytochemical content of the Dietary
Approaches to Stop Hypertension (DASH) diet is higher than in
43. Oliver JJ, Webb DJ. Noninvasive assessment of arterial stiffness
the control study diet. J Am Diet Assoc 2004;104:1725–7.
and risk of atherosclerotic events. Arterioscler Thromb Vasc Biol
26. Pereira MA, O’Reilly E, Augustsson K, Fraser GE, Goldbourt U,
Heitmann BL, et al. Dietary fiber and risk of coronary heart
44. Plotnick GD, Corretti MC, Vogel RA, Hesslink R Jr, Wise JA.
disease: a pooled analysis of cohort studies. Arch Intern Med
Effect of supplemental phytonutrients on impairment of the flow-
mediated brachial artery vasoactivity after a single high-fat meal.
27. Hu FB, Stampfer MJ, Manson JE, Rimm EB, Colditz GA,
J Am Coll Cardiol 2003;41 (10):1744–9.
Rosner BA, et al. Frequent nut consumption and risk of coronary
45. Callister TQ, Raggi P, Cooil B, Lippolis NJ, Russo DJ. Effect of
heart disease in women: prospective cohort study. BMJ 1998;
HMG-CoA reductase inhibitors on coronary artery disease as
assessed by electron-beam computed tomography. N Engl J Med
28. Liu S, Stampfer MJ, Hu FB, Giovannucci E, Rimm E, Manson JE,
et al. Whole-grain consumption and risk of coronary heart disease:
46. Zimlichman R, Shargorodsky M, Boaz M, Duprez D, Rahn KH,
results from the Nurses’ Health Study. Am J Clin Nutr 1999;
Rizzoni D, et al. Determination of arterial compliance using blood
pressure waveform analysis with the CR-2000 system: reliability,
29. Ornish D, Scherwitz LW, Billings JH, Brown SE, Gould KL,
repeatability, and establishment of normal values for healthy
Merritt TA, et al. Intensive lifestyle changes for reversal of coronary
European population—the seven European sites study (SESS).
heart disease. JAMA 1998;280:2001–7.
30. Gardner CD, Coulston A, Chatterjee L, Rigby A, Spiller G,
Farquhar JW. The effect of a plant-based diet on plasma lipids in
Received June 26, 2006; accepted December 4, 2006
Risk of venous thromboembolism in users of oralcontraceptives containing drospirenone or levonorgestrel:nested case-control study based on UK General PracticeResearch DatabaseLianne Parkin, senior lecturer in epidemiology,1 Katrina Sharples, senior lecturer in biostatistics,1 Rohini KHernandez, epidemiologist,2 Susan S Jick, director2Objective To examine the risk of non-fatal idiopathicIn 2002
Analysis of the Cost of Transgender Health Benefits The Cost of Transgender Health Benefits Mary Ann Horton, Ph.D. JPMorgan Chase Transgender at Work ABSTRACT This paper measures the frequency and cost of Transgender Health Benefits (THBs) for US residents. Itreports on a survey of surgeons who do Sex Reassignment Surgery (SRS) procedures, and reports thenumber of US residents