MEDIA RELEASE PR35930
New Insights Link Low HDL-Cholesterol and Elevated Triglycerides With Coronary Heart
Disease and Microvascular Complications in Patients at Goal for LDL-Cholesterol
BARCELONA, Sept 1/ PRNewswire-AsiaNet/ --
- Surveys Establish Residual Vascular Risk is Associated With Atherogenic
Dyslipidemia Suggesting the Need to Reconsider Approach to Management of
Lipids
- Residual Risk Reduction initiative (R3i) Foundation Presents Early
Findings From Unique Global Investigation Into Effects on Residual
Macrovascular and Microvascular Risk
Low levels of high-density lipoprotein cholesterol (HDL-C) and
raised triglycerides, affecting millions of patients worldwide, are strongly
linked to significantly increased risk of coronary heart disease (CHD) even
in patients who achieve or surpass current low density lipoprotein
cholesterol (LDL-C) targets.
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This has been demonstrated in new analyses of the landmark
Prospective Cardiovascular Munster (PROCAM) and the REsiduAl risk Lipids and
Standard Therapies (REALIST) surveys, the latter funded and conducted by the
Residual Risk Reduction Initiative Foundation or R3i. These data have been
presented today at the European Society of Cardiology (ESC) congress.
The final objective of the R3i is to significantly reduce the
incidence of both major macrovascular events and microvascular complications
(e.g. in patients with type 2 diabetes or affected by the metabolic syndrome)
beyond what is already achieved with current treatments.[1],[2]
Earlier studies, largely conducted in patients treated with
statins show that lowering LDL-C to currently recognized goals only reduces
the relative risk of macrovascular disease by about 23 percent.[3]
"The residual vascular risk driven by the increasing epidemic
of obesity, metabolic syndrome and type 2 diabetes is not being adequately
treated by clinicians," stated Professor Frank Sacks from Harvard Medical
School, Boston, USA and Vice-president of R3i. "While LDL-C is appropriately
the current target, we have taken LDL-C reduction to its therapeutic limits
without abolishing CVD events. Therefore we urgently need new strategies to
address other modifiable risk factors such as atherogenic dyslipidemia."
New insights into lipid-related macrovascular risk
Professor Gerd Assmann, member of the R3i International
Steering Committee and President of the Board of the Assmann-Foundation for
Prevention, presented a new analysis from PROCAM in which 823 men who
survived a myocardial infarction (MI) were matched with an equal number of
controls free from MI. This analysis, which was funded by the R3i,
demonstrated:
- Low HDL-C and/or elevated triglycerides (TG) was seen in
nearly two-thirds of MI patients
- When all risks factors were matched, the odds of experiencing a MI were
increased five-fold for men with LDL-C at target (less than or equal to
100mg/dL) presenting a low level of HDL-C (<45 mg/dL) and an elevated
level of TG (>150 mg/dL)
The initial macrovascular findings of REALIST were also
presented by Professor Frank Sacks, Vice-President of the R3i. This
case-control study conducted in 170 patients hospitalized with CHD in Boston,
USA, at goal for LDL-C, matched with 175 controls free from CHD shows that:
- High TG and low HDL-C are strong indicators of residual risk of CHD
- High TG and low HDL-C levels each contribute to the risk of a coronary
event in patients with LDL-C levels less than or equal to 130 mg/dL or
even less than or equal to 70 mg/dL
- TG and HDL-C appear to act synergistically with the impact of TG
increasing when HDL-C is low and the impact of HDL-C increasing when TG
levels are high
- When moving from the lowest levels of TG and highest levels of HDL-C to
the highest levels of TG and lowest levels of HDL-C, the risk of CHD
increases 10-fold
Addressing atherogenic dyslipidemia may reduce the microvascular
complications of type 2 diabetes
REALIST is also evaluating the risk of microvascular
complications in patients with type 2 diabetes who achieve or approach LDL-C
goal. Data collected by Professor Michel Hermans from the Cliniques
Universitaires Saint-Luc in Brussels, Belgium, were presented by Professor
Paola Fioretto, from the Department of Medical and Surgical Sciences,
University of Padua, Italy and showed that:
- Low HDL-C, elevated TG and elevated non-HDL-C levels are more
prevalent in patients who developed microvascular complications
- High TG levels are associated with increased risk of incident
retinopathy, blindness and diabetic kidney disease
- Low HDL-C levels are associated with incident diabetic kidney
disease
Similar to the findings of the macrovascular REALIST survey,
the initial microvascular data showed that patients with incident
microvascular complications of type 2 diabetes are more likely to present
with atherogenic dyslipidemia even when LDL-C is nearly at goal (less than or
equal to 130mg/dL).
"Further analysis of microvascular data from this and other
centers should confirm the relationship between atherogenic dyslipidemia and
microvascular complications of type 2 diabetes," said Professor Fioretto.
Implications of the R3i research program for future treatment
The REALIST research program is being globally extended and
data are currently being collected in 27 centers in 12 countries around the
world. This will support the major global program of education and advocacy
being implemented by the R3i.
The ultimate objective of the R3i Foundation is to identify
new indicators of macro- and microvascular residual risk as targets for
future treatment strategies.
Residual vascular risk - A public health emergency
"Further reduction of LDL-C by use of the maximum permissible
statin dosage is unlikely to be able to substantially lower this residual,
largely non-LDL-C mediated risk," says Professor Gerd Assmann from the
University of Munster, Germany.
Therefore, while statins are effective, other treatment
strategies are urgently needed to address the residual vascular risk which
persists in patients despite current standards of care. While the R3i
research program will help define appropriate targets for intervention in
patients who remain at high residual vascular risk, the ongoing outcomes
trials such as ACCORD, AIM-HIGH and HPS2-THRIVE will help determine new
treatment strategies to address this risk.
"The R3i has a huge task ahead to get people recognizing the
threat of residual vascular risk and acting to better manage it," said
Professor Jean-Charles Fruchart of the University of Lille, France and
President of the R3i. "We have to look beyond using statins as a silver
bullet to reduce LDL-cholesterol. The mindset that reducing one component to
prevent heart disease is wrong and needs to change."
Notes to Editors
More information on the R3i is available from:
Epidemiological study methods
The PROCAM analysis used a case-control approach in which 823
men who had survived a MI were matched with an equal number of controls.
Patients, who were matched for age, smoking status, type 2 diabetes status,
blood pressure and LDL-C to an equal number of MI-free controls from the
PROCAM cohort of 50,000 participants, a unique prospective investigation of
coronary artery disease (CAD) and stroke risk factors in Germany.
The macrovascular REALIST survey was designed to determine, in
patients at goal for LDL-C (less than or equal to 130 mg/dL whether treated
or untreated for elevated LDL-C) with a first or subsequent coronary event,
whether low HDL-C and/or elevated TG levels are associated with a significant
risk of coronary event after adjustment for other risk factors. Adult male or
female patients admitted to coronary care units (CCUs) or explored in cardiac
catheter laboratories were matched with controls hospitalized for other
reasons.
The microvascular REALIST survey was designed to determine
whether low HDL-C and/or elevated TG levels are associated with a significant
residual risk of microvascular complications. Data will be adjusted for other
risk factors such as age, gender, diabetes duration, HbA1C, LDL-C levels,
blood pressure, BMI and smoking status in patients with type 2 diabetes
nearly at goal for LDL-C and presenting with incident microvascular
complication (retinopathy, maculopathy or nephropathy). Diabetic neuropathy
is an exploratory disease due to difficulties in establishing it with
certainty in retrospective analysis. The REALIST surveys are currently being
conducted in Belgium, Croatia, France, Italy, Japan, Philippines, Poland,
Saudi Arabia, Spain, Thailand, Turkey and the U.S.
What is residual vascular risk?
Residual vascular risk is defined as the significant residual
risk of macrovascular events and microvascular complications which persists
in most patients despite current standards of care including achievement of
low-density lipoprotein (LDL-C) goal and intensive control of blood pressure
and blood glucose.
Although statin therapy is the cornerstone of dyslipidemia
management, LDL-C lowering with statins reduces the risk of major coronary
events by approximately one-quarter, with 77 percent of the relative risk of
events still occurring.[3]
Multifactorial intensive therapy (including statins) is
insufficient to prevent the development or progression of microvascular
disease (retinopathy, nephropathy, neuropathy) in up to 50 percent of
patients with type 2 diabetes.[4]
Atherogenic Dyslipidemia and Residual Vascular Risk
Atherogenic dyslipidemia is characterized by elevated TG and
low levels of HDL-C.
In the past three decades in the U.S., while the prevalence of
abnormal levels of LDL-C has decreased, the prevalence of combined abnormal
TG (greater than or equal to 150 mg/dL) and HDL-C (<40 mg/dL) has doubled and
the prevalence of elevated TG (greater than or equal to 150 mg/dL) has
increased five-fold.[5] Elevated TG (>150 mg/dL) is also common, affecting
about 50 percent of adults with prior CVD.[6]
Atherogenic dyslipidemia contributes to the increased risk of
macrovascular events such as myocardial infarction and stroke, and may be
implicated in microvascular complications such as diabetic eye, kidney and
lower limb disease.[7]
- Among patients achieving LDL-C <70 mg/dL with a statin, CVD risk is
almost 60 percent greater for patients with TG >200 mg/dL[8]
- In patients achieving LDL-C <70 mg/dL with a statin, CV risk was higher
in patients with a low HDL-C (HDL-C <37 mg/dL vs. those with a
HDL-C >55 mg/dL)[9]
The mission of R3i
To reduce the significant residual risk of macrovascular
events and microvascular complications which persists in most patients
despite current standards of care including achievement of low density
lipoprotein goal and intensive control of blood pressure and blood glucose.
R3i board of trustees
Professor Jean-Charles Fruchart, President Institut Pasteur de
Lille Universite, Lille2,
Lille, France
Professor Frank Sacks, Vice-President Harvard School of Public
Health and Harvard Medical
School, Boston, USA
Professor Michel P. Hermans, Cliniques Universitaires
General Secretary Saint-Luc, Brussels, Belgium
References:
---------------------------------
[1] Fruchart JC, Sacks F, Hermans MP, Assmann G, Brown WV, Ceska R, et
al. The Residual Risk Reduction Initiative: a call to action to reduce
residual vascular risk in patients with dyslipidemia. Am J Cardiol. 2008;102
(Suppl):1K-34K.
[2] Fruchart JC, Sacks F, Hermans MP, Assmann G, Brown WV, Ceska R, et
al. The Residual Risk Reduction Initiative: a call to action to reduce
residual vascular risk in patients with dyslipidemia. Diab Vasc Dis Res.
2008; 5:319-35.
[3] Baigent C, Keech A, Kearney PM, Blackwell L, Buck G,
Pollicino C, et al; Cholesterol Treatment Trialists' (CTT) Collaborators.
Efficacy and safety of cholesterol-lowering treatment: prospective
meta-analysis of data from 90,056 participants in 14 randomised trials of
statins. Lancet. 2005;366:1267-78
[4] Gaede P, Vedel P, Larsen N, Jensen GV, Parving HH,
Pedersen O. Multifactorial intervention and cardiovascular disease in
patients with type 2 diabetes. N Engl J Med. 2003;348:383-393
[5] Alsheikh-Ali AA, Lin JL, Abourjaily P, Ahearn D, Kuvin JT,
Karas RH. Prevalence of low highdensity lipoprotein cholesterol in patients
with documented coronary heart disease or riskequivalent and controlled
low-density lipoprotein cholesterol. Am J Cardiol. 2007;100:1499-1501
[6] Ninomiya JK, L'Italien G, Criqui MH, Whyte JL, Gamst A,
Chen RS. Association of the metabolic syndrome with history of myocardial
infarction and stroke in the Third National Health and Nutrition Examination
Survey. Circulation. 2004;109:42-46
[7] Isomaa B, Almgren P, Tuomi T, Forsen B, Lahti K, Nissen M,
Taskinen MR, Groop L. Cardiovascular morbidity and mortality associated with
the metabolic syndrome. Diabetes Care. 2001;24:683-689
[8] Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald
E. Impact of triglyceride levels beyond low-density lipoprotein cholesterol
after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll
Cardiol. 2008;51:724-730
[9] Barter P, Gotto AM, LaRosa JC, Maroni J, Szarek M, Grundy SM,
Kastelein JJ, Bittner V, Fruchart JC. HDL cholesterol, very low levels of LDL
cholesterol, and cardiovascular events. N Engl J Med. 2007;357:1301-1310
SOURCE: Residual Risk Reduction Initiative
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