News & Analysis
Medical News & Perspectives
Cardiovascular Corner
Low Lipids, Metformin, and Plant-Based Diets
Jennifer Abbasi
T
his Medical News series offers an oc-
casional roundup of developments in
cardiovascular medicine.
Women’s stroke risk factors, a diabetes
drug for heart disease, and a meta-analysis
of diets made the news in recent months.
Low Lipids and Hemorrhagic Stroke
Very low levels of low-density lipoprotein
cholesterol (LDL-C) or low levels of triglyc-
erides were associated with an increased risk
of hemorrhagic stroke among women in
a prospective cohort study recently pub-
lished in Neurology. Prior studies have linked
low lipid levels to bleeding strokes, but sex-
specific data haven’t been available until now.
Researchers examined data from 27 937
participants in the Women’s Health Study,
most of whom were not taking lipid-
lowering therapies at baseline. Over an av-
erage 19.3 years of follow-up, there were 137
incidents of hemorrhagic stroke. The strokes
were more than twice as likely to occur
among the 3.8% of women with LDL-C lev-
els lower than 70 mg/dL relative to those
with levels ranging from 100 to 129.9 mg/dL,
the reference range. And compared with
women in the top quartile of triglycerides,
those in the lowest quartile also had 2 times
the risk of hemorrhagic stroke.
Although very low LDL-C levels are not
considered a risk factor for heart attack and
ischemic stroke, the findings suggest this
may not be the case for hemorrhagic stroke.
Low cholesterol may affect the integrity of
the vessel walls, making them more suscep-
Molecule Data Source: DrugBank Accession No. APRD01099
tible to bleeding events, said lead study au-
thor Pamela Rist, ScD, an associate epide-
miologist at Brigham and Women’s Hospital
and an assistant professor of medicine at
Harvard Medical School in Boston. Given
this, it’s “important to manage other risk fac-
tors for hemorrhagic stroke among these
women, such as hypertension or smoking,”
Rist told JAMA.
Women with LDL-C levels ranging from
130 to 159.9 mg/dL or 70 to 99.9 mg/dL did
not have a greater risk of hemorrhagic stroke
in the study. But the researchers did find
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a nonsignificant suggestion of increased risk
in women with high levels of LDL-C at or
above 160 mg/dL. Other studies have not ex-
plored whether high LDL-C levels are asso-
ciated with hemorrhagic strokes, according
to Rist, so further research is needed.
Metformin’s Cardioprotective Effect
A 2000-mg daily dose of metformin im-
proved left ventricular hypertrophy (LVH) in
a proof-of-concept randomized clinical trial
involving 68 patients who did not have dia-
betes but had coronary artery disease (CAD)
and insulin resistance, prediabetes, or both.
Published recently in the European Heart
Journal, the results bolster observational
data that suggest metformin is cardiopro-
tective and raise the possibility of using the
drug in patients with CAD who don’t have
diabetes, the study’s authors said.
Metformin
A serious risk factor for adverse car-
diovascular outcomes, LVH—thickening of
the heart’s main pumping chamber—is
largely a consequence of high blood pres-
sure. However, normotensive patients
with obesity or insulin resistance can also
develop the condition, highlighting the
need for new treatment strategies beyond
blood pressure control.
In the 12-month trial, prolonged-
release metformin significantly reduced
left ventricular mass indexed to height
compared with placebo. The diabetes drug
(Reprinted) JAMA Published online June 12, 2019
also reduced body weight, systolic blood
pressure, and a biomarker for oxidative
stress—changes that could underpin its
effect on LVH, according to Chim Lang,
MD, the study’s senior author and head of
the division of molecular and clinical medi-
cine at the University of Dundee School of
Medicine in Scotland.
The results from an ongoing larger trial
could provide conclusive evidence of met-
formin’s cardioprotective effects, Lang said.
Red Meat vs Plant-Based Protein
Substituting red meat with high-quality
plant protein sources was associated with
more favorable changes in cardiovascular
risk factors relative to dietary replace-
ments combined in a recent meta-analysis
of randomized clinical trials (RCTs) pub-
lished in Circulation.
Previous findings from RCTs that evalu-
ated the effects of red meat on cardiovascu-
lar disease risk factors have been inconsis-
tent. However, when comparing outcomes,
those studies combined non–red meat
diets, which varied considerably in quality
and composition.
The new study, which included 36 trials
involving 1803 participants, is the first to
separately compare diets high in red meat
with those high in other types of foods, ac-
cording to lead author Marta Guasch-Ferré,
PhD, a research scientist in the department
of nutrition at the Harvard T.H. Chan School
of Public Health in Boston. Comparison diets
were stratified by high-quality plant pro-
tein; chicken, poultry, and fish; fish only;
poultry only; mixed animal protein sources
including dairy; low-quality refined grains
and simple sugars; or usual diet.
Based on this analysis, diets with more
high-quality plant protein from sources such
as legumes, soy, and nuts were linked to
lower levels of both total and LDL choles-
terol compared with red-meat heavy diets.
However, when diets with red meat were
compared with all other types of diets com-
bined, no significant differences in total cho-
lesterol, lipoproteins, or blood pressure were
E1
 News & Analysis
found. Only triglyceride levels were el-
evated with red meat consumption com-
pared with other diets combined.
Surprisingly, red meat-heavy diets ap-
peared to lower cholesterol levels more than
fish diets. Long-term, well-designed stud-
ies are needed to confirm this. “The poten-
tially beneficial effects of red meat consump-
tion versus fish on total cholesterol and
LDL-C observed in our analyses may mostly
reflect studies in which participants con-
sumed lean, unprocessed meat and both in-
terventions adhered to nutritional recom-
mendations,” Guasch-Ferré said.
E2 JAMA Published online June 12, 2019 (Reprinted)
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“The main takeaway message should be
to encourage the intake of legumes, nuts,
vegetable fats, oils, and other foods from
plant sources while the intake of animal fats,
and particularly red and processed meat,
should be discouraged,” she added.
The findings also underscore the
importance of the comparison diet when
assessing the effects of nutrients or foods,
Guasch-Ferré said. High-quality plant pro-
tein sources generally have higher propor-
tions of polyunsaturated fatty acids and
fiber than red meat, and no cholesterol,
potentially leading to health improve-
ments, but red meat may have null or
more beneficial effects on cardiovascular
risk factors than do refined grains or
added sugars.
However, Guasch-Ferré cautioned that
most of the individual studies included in the
meta-analysis were small and that dietary in-
tervention trials sometimes have low com-
pliance, which could minimize differences
between comparison diets. She also noted
that the total diet could modify the effects
of individual foods on lipid parameters.
Note: Source references are available through
embedded hyperlinks in the article text online.
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