|Aggressively Lowering Cholesterol and Blood
Pressure May Reverse Atherosclerosis in Adults with Diabetes
Aggressively lowering cholesterol and blood pressure levels below
current targets in adults with type 2 diabetes may help to prevent — and
possibly reverse — hardening of the arteries, according to
new research supported by the National Heart, Lung, and Blood Institute
(NHLBI) of the National Institutes of Health. Hardening of the
arteries, also known as atherosclerosis, is the number one cause
of heart disease and can lead to heart attack, stroke, and death.
The three-year study of 499 participants is the first to compare
two treatment targets for LDL ("bad") cholesterol and
systolic blood pressure levels, key risk factors for heart disease,
in people with diabetes. Results are published in the April 9 issue
of the Journal of the American Medical Association.
"This study provides good news for adults with type 2 diabetes," said
Elizabeth G. Nabel, M.D., NHLBI director. "These patients
are two to four times more likely than people without diabetes
to die from heart disease. For the first time, we have evidence
that aggressively lowering LDL cholesterol and blood pressure can
actually reverse damage to the arteries in middle-aged adults with
In the Stop Atherosclerosis in Native Diabetics Study (SANDS),
approximately one-half of the participants (247) were asked to
lower to standard levels their LDL cholesterol (to 100 milligrams
per deciliter) and blood pressure (systolic blood pressure of 130
mmHg or lower), while the other half (252) aimed for more aggressive
lowering of LDL cholesterol to 70 mg/dL or lower and of systolic
blood pressure to 115 mmHg or lower. All participants were American
Indians 40 years or older (average age of 56) who had diabetes,
high blood cholesterol, and high blood pressure but no history
of heart attack or other evidence of heart disease. The study was
conducted at four clinical centers in southwestern Oklahoma; Phoenix,
Ariz.; northeastern Arizona; and South Dakota. All participants
continued to receive their medical care, including diabetes management,
dietary and exercise counseling, and smoking cessation, from their
health care providers with the Indian Health Service. Like the
NIH, the Indian Health Service is part of the U.S. Department of
Health and Human Services.
"American Indians have a high rate of diabetes and cardiovascular
disease related to diabetes, but there are few clinical trials
that address these issues in this population," said Barbara
V. Howard, Ph.D., of MedStar Research Institute in Hyattsville,
Md., lead author of the paper. "These study results provide
needed evidence to help develop community-based programs to treat
and prevent the epidemic of cardiovascular disease among American
Indians. At the same time, we are increasing our understanding
of the effects of intensively lowering cholesterol and blood pressure
in adults with type 2 diabetes, which might also apply to other
During the three-year study, participants were examined by study
clinicians one month after enrollment, then every three months,
to assess their blood cholesterol and blood pressure levels and
general well being. Food and Drug Administration-approved blood
pressure and cholesterol medications were added and adjusted as
needed to help participants achieve their treatment goals. The
same medications were available to participants in the standard
and the aggressive treatment groups. Participants were also encouraged
to follow lifestyle approaches to help meet their blood pressure
and cholesterol treatment targets, such as following a heart-healthy
eating plan, being physically active, maintaining a healthy weight,
and not smoking.
To assess the impact of the treatments on the participants' cardiovascular
health, researchers used ultrasound to measure the thickness of
the carotid (neck) artery — an indication of hardening of
the arteries, a leading effect of high blood pressure and cholesterol
and an early sign of cardiovascular disease. In addition, ultrasound
was also used to measure the size and function of the left ventricle,
the heart's main pumping chamber. Enlarged hearts are known to
be predictors of increased risk of heart attack and stroke. These
measurements were taken at enrollment, at 18 months, and at 36
months, when the study ended.
On average, participants in both groups reached and maintained
their target goals for blood cholesterol and blood pressure levels.
The numbers of heart attacks and other cardiovascular events were
similar between the two groups and lower than expected.
In addition, carotid artery thickness measurements of participants
in the aggressive treatment group were significantly lower than
those in the standard treatment group. Researchers report that,
compared to baseline, carotid artery thickness increased slightly
in the standard group and regressed in the aggressive treatment
group, indicating a partial reversal of atherosclerosis. Furthermore,
although heart size decreased from baseline in both groups, the
beneficial change was significantly greater among participants
in the aggressive treatment group.
"Many patients with diabetes do not reach their blood pressure
and cholesterol goal levels and thus remain at high risk for heart
attacks and stroke," noted Howard. "In our study, participants
successfully managed their blood cholesterol and blood pressure
to reach their goal levels. Our message to doctors, nurses, and
patients is that you can reach your goal levels, and we should
work together to help you do that."
As with any therapy, the benefits and risks must be considered
for each patient. In SANDS, participants in the aggressive treatment
group on average needed more medications and higher doses than
the standard treatment group, and they were slightly more likely
to have side effects from blood pressure-lowering medications than
those in the standard group. Such adverse effects generally resolved,
however, after the medication was changed or the dose reduced.
There were no differences in side effects related to cholesterol-lowering
drugs between the standard and the aggressive treatment groups.
"These encouraging findings from SANDS suggest that more
aggressive blood pressure and cholesterol targets than those currently
recommended in patients with diabetes may reduce their future cardiovascular
risk," said Jerome L. Fleg, M.D., NHLBI project officer of
the study and a coauthor of the paper. "Longer term followup
of this population as well as additional studies in other populations
are needed to confirm the benefit and cost-effectiveness of these
Medications used in this study were donated by First Horizon Pharmacy,
Merck and Co., and Pfizer, Inc.
An estimated 21 million Americans have diabetes and 284,000 die
from it each year. Sixty-five percent of the deaths are related
to cardiovascular causes.
To arrange an interview with an NHLBI spokesperson, please contact
the NHLBI Communications Office at (301) 496-4236 or email email@example.com.
To interview Dr. Howard through April 9, please contact NHLBI;
after April 10, please contact Dr. Howard at 301-602-0125 or her
assistant at 301-560-7305.
Part of the National Institutes of Health, the National Heart,
Lung, and Blood Institute (NHLBI) plans, conducts, and supports
research related to the causes, prevention, diagnosis, and treatment
of heart, blood vessel, lung, and blood diseases; and sleep disorders.
The Institute also administers national health education campaigns
on women and heart disease, healthy weight for children, and other
topics. NHLBI press releases and other materials are available
online at www.nhlbi.nih.gov.
The National Institutes of Health (NIH) — The Nation's
Medical Research Agency — includes 27 Institutes and
Centers and is a component of the U.S. Department of Health and
Human Services. It is the primary federal agency for conducting
and supporting basic, clinical and translational medical research,
and it investigates the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and
its programs, visit www.nih.gov.