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A New Way to Combat Weight Gain
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We’ve all heard about the importance of raising HDL, or the so-called “good”
cholesterol, and lowering LDL, or “bad” cholesterol, to improve heart health. While
we’ve come to assume HDL cholesterol is an inherently good thing, a new study
shows that for a certain group of patients, this is not always the case. The study is
the first to find that a high level of the supposedly good cholesterol places a
subgroup of patients at high risk for recurrent coronary events, such as chest pain,
heart attack, and death.
The findings, published in Arteriosclerosis, Thrombosis, and Vascular Biology, a
journal of the American Heart Association, could help explain disappointing
results from a high-profile Pfizer clinical trial testing torcetrapib, an experimental
drug designed to increase levels of HDL cholesterol, that some predicted would
become a blockbuster medicine. The trial was halted in 2006 due to a surprisingly
excessive number of cardiovascular events and death. As in the current study,
cardiovascular events in the torcetrapib trial were associated with higher levels of
“good” HDL cholesterol, though the reasons were unclear.
“It seems counterintuitive that increasing good cholesterol, which we’ve always
thought of as protective, leads to negative consequences in some people,”
saidJames Corsetti, M.D., Ph.D., professor of Pathology and Laboratory Medicine
at the University of Rochester Medical Center and lead author of the study. “We’ve
confirmed that high HDL cholesterol is in fact associated with risk in a certain
group of patients.”
Using a novel graphical data mapping tool – outcome event mapping – Corsetti
and his team identified a group of patients in which elevated levels of HDL
cholesterol place them in a high-risk category for coronary events.
“The ability to identify patients who will not benefit from efforts to increase HDL
cholesterol is important because they can be excluded from trials testing
medications that aim to raise HDL cholesterol,” said Charles Sparks, M.D.,
professor of Pathology and Laboratory Medicine and co-author of the study. “With
these patients excluded, researchers may find that raising HDL cholesterol in the
remaining population is effective in reducing cardiovascular disease risk.”
Despite the outcome of the Pfizer torcetrapib trial and findings in the existing
literature, including the current study, that suggest high HDL cholesterol can be a
bad thing, drug companies remain invested in identifying drugs to increase HDL
cholesterol. Merck recently announced plans to launch a major clinical trial in
2011 to test whether anacetrapib – a molecular cousin to torcetrapib designed to
raise good cholesterol – reduces the risk of heart attack and death.
Patients in the high-risk subgroup were characterized as having high levels of C-
reactive protein (CRP), a well-known marker of inflammation, in addition to high
HDL cholesterol. Study authors believe genetics and environmental factors,
particularly inflammation, influence whether high levels of HDL cholesterol are
protective or if they increase cardiovascular risk in individual patients. Given an
inflammatory environment, an individual’s unique set of genes helps determine
whether HDL cholesterol transforms from a good actor to a bad actor in the heart
disease process.
In the high-risk subgroup of patients with elevated HDL cholesterol and CRP,
researchers also identified two genetic factors associated with recurrent coronary
events. The activity of cholesterol ester transfer protein (CETP), which moves
cholesterol away from the vascular system and is associated with HDL
cholesterol, and p22phox, which influences inflammation-related processes and
is associated with CRP, are both risk predictors in this subgroup of patients.
“Our research is oriented around the ability to better identify patients at high risk,”
said Corsetti. “Identifying these patients and determining what puts them at high
risk may be useful in choosing treatments tailored to the specific needs of
particular patient subgroups. This gets us another step closer to achieving the
goal of personalized medicine.”
Corsetti’s team identified individuals at high risk for recurrent coronary events
among 767 non-diabetic patients who experienced at least one prior heart attack.
About 20 percent of the total study population was in the subgroup having high-
risk with high HDL cholesterol and CRP. Outcome event maps plot risk over an
area defined by high and low levels of two biomarkers, in this case HDL
cholesterol and CRP. Peaks and valleys in the maps correspond to high- and low-
risk patient subgroups. Patients were followed for recurrent events for
approximately two years and were part of the Thrombogenic Factors and
Recurrent Coronary Events (THROMBO) study led by cardiologist Arthur Moss, M.
D., professor of Medicine at the University of Rochester Medical Center and study
co-author.
The current results parallel findings from a study of a healthy population. The
Prevention of Renal and Vascular End-Stage Disease (PREVEND) study also
identified a high-risk subgroup of patients with elevated HDL cholesterol and CRP
levels among individuals who had no prior coronary events.
In addition to Corsetti, Sparks, and Moss, Dan Ryan, M.D., and Wojciech Zareba,
M.D., Ph.D. from the University of Rochester Medical Center and David Rainwater,
Department of Genetics, Southwest Foundation for Biomedical Research, San
Antonio, Texas participated in the study. The study was funded by the National
Heart, Lung and Blood Institute at the National Institutes of Health.
cholesterol, and lowering LDL, or “bad” cholesterol, to improve heart health. While
we’ve come to assume HDL cholesterol is an inherently good thing, a new study
shows that for a certain group of patients, this is not always the case. The study is
the first to find that a high level of the supposedly good cholesterol places a
subgroup of patients at high risk for recurrent coronary events, such as chest pain,
heart attack, and death.
The findings, published in Arteriosclerosis, Thrombosis, and Vascular Biology, a
journal of the American Heart Association, could help explain disappointing
results from a high-profile Pfizer clinical trial testing torcetrapib, an experimental
drug designed to increase levels of HDL cholesterol, that some predicted would
become a blockbuster medicine. The trial was halted in 2006 due to a surprisingly
excessive number of cardiovascular events and death. As in the current study,
cardiovascular events in the torcetrapib trial were associated with higher levels of
“good” HDL cholesterol, though the reasons were unclear.
“It seems counterintuitive that increasing good cholesterol, which we’ve always
thought of as protective, leads to negative consequences in some people,”
saidJames Corsetti, M.D., Ph.D., professor of Pathology and Laboratory Medicine
at the University of Rochester Medical Center and lead author of the study. “We’ve
confirmed that high HDL cholesterol is in fact associated with risk in a certain
group of patients.”
Using a novel graphical data mapping tool – outcome event mapping – Corsetti
and his team identified a group of patients in which elevated levels of HDL
cholesterol place them in a high-risk category for coronary events.
“The ability to identify patients who will not benefit from efforts to increase HDL
cholesterol is important because they can be excluded from trials testing
medications that aim to raise HDL cholesterol,” said Charles Sparks, M.D.,
professor of Pathology and Laboratory Medicine and co-author of the study. “With
these patients excluded, researchers may find that raising HDL cholesterol in the
remaining population is effective in reducing cardiovascular disease risk.”
Despite the outcome of the Pfizer torcetrapib trial and findings in the existing
literature, including the current study, that suggest high HDL cholesterol can be a
bad thing, drug companies remain invested in identifying drugs to increase HDL
cholesterol. Merck recently announced plans to launch a major clinical trial in
2011 to test whether anacetrapib – a molecular cousin to torcetrapib designed to
raise good cholesterol – reduces the risk of heart attack and death.
Patients in the high-risk subgroup were characterized as having high levels of C-
reactive protein (CRP), a well-known marker of inflammation, in addition to high
HDL cholesterol. Study authors believe genetics and environmental factors,
particularly inflammation, influence whether high levels of HDL cholesterol are
protective or if they increase cardiovascular risk in individual patients. Given an
inflammatory environment, an individual’s unique set of genes helps determine
whether HDL cholesterol transforms from a good actor to a bad actor in the heart
disease process.
In the high-risk subgroup of patients with elevated HDL cholesterol and CRP,
researchers also identified two genetic factors associated with recurrent coronary
events. The activity of cholesterol ester transfer protein (CETP), which moves
cholesterol away from the vascular system and is associated with HDL
cholesterol, and p22phox, which influences inflammation-related processes and
is associated with CRP, are both risk predictors in this subgroup of patients.
“Our research is oriented around the ability to better identify patients at high risk,”
said Corsetti. “Identifying these patients and determining what puts them at high
risk may be useful in choosing treatments tailored to the specific needs of
particular patient subgroups. This gets us another step closer to achieving the
goal of personalized medicine.”
Corsetti’s team identified individuals at high risk for recurrent coronary events
among 767 non-diabetic patients who experienced at least one prior heart attack.
About 20 percent of the total study population was in the subgroup having high-
risk with high HDL cholesterol and CRP. Outcome event maps plot risk over an
area defined by high and low levels of two biomarkers, in this case HDL
cholesterol and CRP. Peaks and valleys in the maps correspond to high- and low-
risk patient subgroups. Patients were followed for recurrent events for
approximately two years and were part of the Thrombogenic Factors and
Recurrent Coronary Events (THROMBO) study led by cardiologist Arthur Moss, M.
D., professor of Medicine at the University of Rochester Medical Center and study
co-author.
The current results parallel findings from a study of a healthy population. The
Prevention of Renal and Vascular End-Stage Disease (PREVEND) study also
identified a high-risk subgroup of patients with elevated HDL cholesterol and CRP
levels among individuals who had no prior coronary events.
In addition to Corsetti, Sparks, and Moss, Dan Ryan, M.D., and Wojciech Zareba,
M.D., Ph.D. from the University of Rochester Medical Center and David Rainwater,
Department of Genetics, Southwest Foundation for Biomedical Research, San
Antonio, Texas participated in the study. The study was funded by the National
Heart, Lung and Blood Institute at the National Institutes of Health.
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