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Lower target
Blood Pressure, LDL-Cholesterol may provide
Cardiovascular benefits
Newswise — Patients
with diabetes who reduced their blood
pressure and LDL-cholesterol to below
standard target levels had a greater
decrease in carotid artery wall thickness,
but did not have a significant difference in
cardiovascular disease events than patients
who had recommended blood pressure and LDL-cholesterol
levels, according to a study in the April 9
issue of JAMA.
Individuals with
diabetes are at increased risk for
developing cardiovascular disease (CVD), and
coronary heart disease (CHD) is the leading
cause of death in adults with diabetes,
according to background information in the
article.
The increased
diabetes-associated CVD risk is due in large
part to higher prevalences of other major
CVD risk factors, such as dyslipidemia
(disorders of lipoprotein metabolism, which
includes high cholesterol levels) and
hypertension.
Some studies have
suggested that lowering systolic blood
pressure (SBP) and low-density lipoprotein
cholesterol (LDL-C) below recommended levels
in patients with diabetes may be beneficial
regarding CVD.
Barbara V. Howard,
Ph.D., of MedStar Research Institute,
Hyattsville, Md., and colleagues conducted
SANDS (Stop Atherosclerosis in Native
Diabetics Study), a clinical trial that
compared the progression of subclinical
atherosclerotic disease (process in which
plaque builds up in the inner lining of the
arteries) in 499 American Indian men and
women with type 2 diabetes, randomly
assigned either to reach aggressive targets
of LDL-C of 70 mg/dL or lower plus SBP of
115 mm Hg or lower or to reach standard
targets of LDL-C of 100 mg/dL or lower and
SBP of 130 mm Hg or lower. American Indians
have a high prevalence of diabetes and
diabetes-related CVD.
The 3-year trial was
conducted at four clinical centers in
Oklahoma, Arizona and South Dakota.
Average target LDL-C
and SBP levels for both groups were reached
and maintained. Compared with baseline,
intimal medial thickness (IMT; measurement
of thickness of the wall in an artery and a
marker for atherosclerosis) regressed in the
aggressive treatment group and progressed in
the standard treatment group; carotid
arterial (one of two major arteries)
cross-sectional area also regressed.
Rates of adverse events
(38.5 percent and 26.7 percent) and serious
adverse events (n = 4 vs. 1) related to
blood pressure medications were higher in
the aggressive group. Clinical CVD events
did not differ significantly between groups.
“Although there were no
differences in clinical CVD outcomes, event
rates were low in both groups, and
progression of subclinical disease in the
standard treatment group was lower than
expected.
"The
data suggest that targeted treatment of LDL-C
and SBP improved surrogate measures of CVD,
with greater benefits being attributable to
the lower target levels.
"Conversely,
the lack of difference in occurrence of
events and the increase in adverse events
and serious adverse events attributable to
the BP lowering raise the possibility that
there may not be favorable long-term
outcomes.
"Whether
the strategy of more aggressive targets for
either LDL-C or BP will result in lower
long-term CVD event rates or economic
benefit remains to be determined.”
Editor’s Note: Please
see the article for additional information,
including other authors, author
contributions and affiliations, financial
disclosures, funding and support, etc.
Editorial: The Great Debate of 2008—How Low
to Go in Preventive Cardiology?
In an accompanying
editorial, Eric D. Peterson, M.D., M.P.H.,
and Tracy Y. Wang, M.D., M.S., of Duke
University Medical Center, Durham, N.C.,
(Dr. Peterson is also Contributing Editor,
JAMA), comment on the findings of Howard and
colleagues.
“What are the take-home
messages from SANDS? For the true believers,
the study confirms that aggressive lipid and
hypertension treatment has a favorable
effect on proven ‘early markers’ of disease.
"Thus,
with longer duration of follow-up (which
will hopefully be the case), the study would
most assuredly demonstrate improved patient
outcomes. For the therapeutic nihilists,
however, SANDS took high-risk patients with
type 2 diabetes, studied them under
idealized circumstances, and still found no
clinical benefit after 3 years of follow-up.
"In
fact, an aggressive approach involved
greater polypharmacy and costs and had a
higher risk of adverse effects.”
“In conclusion, SANDS
is an important step forward in discovering
whether lower goals are truly better for
primary prevention.
"While
the study results can be interpreted to
support both viewpoints on the ideal target
of therapy, such debates are healthy and
will ultimately drive physicians to search
for more definitive evidence as well as to
seek system-wide strategies to effectively
reach therapeutic goals in community
practice,” they write.
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