> Narrative Review: Lack of Evidence for Recommended Low-Density
> Lipoprotein Treatment Targets: A Solvable Problem
>  Rodney A. Hayward, MD; Timothy P. Hofer, MD, MSc; and Sandeep Vijan,
> MD, MSc

> Recent national recommendations have proposed that physicians should
> titrate lipid therapy to achieve low-density lipoprotein (LDL)
> cholesterol levels less than 1.81 mmol/L (<70 mg/dL) for patients at
> very high cardiovascular risk and less than 2.59 mmol/L (<100 mg/dL)
> for patients at high cardiovascular risk. To examine the clinical
> evidence for these recommendations, the authors sought to review all
> controlled trials, cohort studies, and case-control studies that
> examined the independent relationship between LDL cholesterol and
> major cardiovascular outcomes in patients with LDL cholesterol levels
> less than 3.36 mmol/L (<130 mg/dL).

> For those with LDL cholesterol levels less than 3.36 mmol/L (<130 mg/
> dL), the authors found no clinical trial subgroup analyses or valid
> cohort or case-control analyses suggesting that the degree to which
> LDL cholesterol responds to a statin independently predicts the
> degree
> of cardiovascular risk reduction. Published studies had avoidable
> limitations, such as a reliance on ecological (aggregate) analyses,
> use of analyses that ignore statins' other proposed mechanisms of
> action, and failure to account for known confounders (especially
> healthy volunteer effects). Clear, compelling evidence supports near-
> universal empirical statin therapy in patients at high cardiovascular
> risk (regardless of their natural LDL cholesterol values), but
> current
> clinical evidence does not demonstrate that titrating lipid therapy
> to
> achieve proposed low LDL cholesterol levels is beneficial or safe.

> Thanks Vince

> >http://www.annals.org/cgi/content/abstract/145/7/520

> > Narrative Review: Lack of Evidence for Recommended Low-Density
> > Lipoprotein Treatment Targets: A Solvable Problem
> >  Rodney A. Hayward, MD; Timothy P. Hofer, MD, MSc; and Sandeep Vijan,
> > MD, MSc

> > Recent national recommendations have proposed that physicians should
> > titrate lipid therapy to achieve low-density lipoprotein (LDL)
> > cholesterol levels less than 1.81 mmol/L (<70 mg/dL) for patients at
> > very high cardiovascular risk and less than 2.59 mmol/L (<100 mg/dL)
> > for patients at high cardiovascular risk. To examine the clinical
> > evidence for these recommendations, the authors sought to review all
> > controlled trials, cohort studies, and case-control studies that
> > examined the independent relationship between LDL cholesterol and
> > major cardiovascular outcomes in patients with LDL cholesterol levels
> > less than 3.36 mmol/L (<130 mg/dL).

> > For those with LDL cholesterol levels less than 3.36 mmol/L (<130 mg/
> > dL), the authors found no clinical trial subgroup analyses or valid
> > cohort or case-control analyses suggesting that the degree to which
> > LDL cholesterol responds to a statin independently predicts the
> > degree
> > of cardiovascular risk reduction. Published studies had avoidable
> > limitations, such as a reliance on ecological (aggregate) analyses,
> > use of analyses that ignore statins' other proposed mechanisms of
> > action, and failure to account for known confounders (especially
> > healthy volunteer effects). Clear, compelling evidence supports near-
> > universal empirical statin therapy in patients at high cardiovascular
> > risk (regardless of their natural LDL cholesterol values), but
> > "current
> > clinical evidence does not demonstrate that titrating lipid therapy
> > to
> > achieve proposed low LDL cholesterol levels is beneficial or safe."

> > Thanks Vince

> According to the study, yes, hi dose statins are worth it.

> Did you miss that?

> L.- Hide quoted text -

> - Show quoted text -

>> >http://www.annals.org/cgi/content/abstract/145/7/520

>> > Narrative Review: Lack of Evidence for Recommended Low-Density
>> > Lipoprotein Treatment Targets: A Solvable Problem
>> >  Rodney A. Hayward, MD; Timothy P. Hofer, MD, MSc; and Sandeep
Vijan,
>> > MD, MSc

>> > Recent national recommendations have proposed that physicians should
>> > titrate lipid therapy to achieve low-density lipoprotein (LDL)
>> > cholesterol levels less than 1.81 mmol/L (<70 mg/dL) for patients at
>> > very high cardiovascular risk and less than 2.59 mmol/L (<100 mg/dL)
>> > for patients at high cardiovascular risk. To examine the clinical
>> > evidence for these recommendations, the authors sought to review all
>> > controlled trials, cohort studies, and case-control studies that
>> > examined the independent relationship between LDL cholesterol and
>> > major cardiovascular outcomes in patients with LDL cholesterol
levels
>> > less than 3.36 mmol/L (<130 mg/dL).

>> > For those with LDL cholesterol levels less than 3.36 mmol/L (<130
mg/
>> > dL), the authors found no clinical trial subgroup analyses or valid
>> > cohort or case-control analyses suggesting that the degree to which
>> > LDL cholesterol responds to a statin independently predicts the
>> > degree
>> > of cardiovascular risk reduction. Published studies had avoidable
>> > limitations, such as a reliance on ecological (aggregate) analyses,
>> > use of analyses that ignore statins' other proposed mechanisms of
>> > action, and failure to account for known confounders (especially
>> > healthy volunteer effects). Clear, compelling evidence supports
near-
>> > universal empirical statin therapy in patients at high
cardiovascular
>> > risk (regardless of their natural LDL cholesterol values), but
>> > "current
>> > clinical evidence does not demonstrate that titrating lipid therapy
>> > to
>> > achieve proposed low LDL cholesterol levels is beneficial or safe."

>> > Thanks Vince

>> According to the study, yes, hi dose statins are worth it.

>> Did you miss that?

>> L.- Hide quoted text -

>> - Show quoted text -

> not according to the abstract. "...current
>  clinical evidence does not demonstrate that titrating lipid therapy
>  to achieve proposed low LDL cholesterol levels is beneficial or
> safe."

> not according to the abstract. "...current
>  clinical evidence does not demonstrate that titrating lipid therapy
>  to achieve proposed low LDL cholesterol levels is beneficial or
> safe."- Hide quoted text -

> > not according to the abstract. "...current
> >  clinical evidence does not demonstrate that titrating lipid therapy
> >  to achieve proposed low LDL cholesterol levels is beneficial or
> > safe."- Hide quoted text -

> This article looks at several issues . The {*filter*}pin that guides all
> statin treatment is questioned all from cited article.........
> "In 2004, a National Cholesterol Education Program (NCEP) expert panel
> recommended that physicians titrate lipid therapy to reach a low-
> density lipoprotein (LDL) cholesterol level less than 1.81 mmol/L (<70
> mg/dL) in patients at very high risk for cardiovascular events (1, 2).
> The panel stated that consistent and compelling evidence showed a
> strong relationship between LDL cholesterol level and cardiovascular
> outcomes down to this level (1, 2). However, others have reviewed the
> same literature and have concluded that there is no valid evidence
> from clinical trials (see Glossary) supporting this
> conclusion ........."  and looked at the reliability of TC as a
> predictior of risk......"These results raised questions about whether
> the strong association found at higher levels of LDL cholesterol could
> be extended to lower LDL cholesterol levels; they also raised concerns
> that total LDL cholesterol is an unreliable marker of benefit and may
> be confounded by dietary factors or LDL subparticles that are the true
> causal factors (7-11). .........

> It also questions  one of the  prime rational behind statin guidelines

> "The experts from the NCEP stated the following:

> Recent clinical trials nonetheless have documented ... that for every
> 1% reduction in LDL-C [low-density lipoprotein cholesterol] levels,
> relative risk for major CHD [coronary heart disease] events is reduced
> by approximately 1%. HPS [Heart Protection Study] data suggest that
> this relationship holds for LDL-C levels even below 100 mg/dL [2.59
> mmol/L].'......

> And noted the lack of evidence for that statement .......

> " Almost all published clinical trials examined fixed doses of statins
> (placebo vs. statin or low-dose vs. high-dose statins), and no
> published trial examined titrating lipid therapy to the proposed LDL
> cholesterol goals. Therefore, the main results of these trials could
> not be used to support or refute the benefits of titrating lipid
> therapy to try to achieve these LDL cholesterol targets. We found only
> 1 valid experimental subgroup analysis of this question, which does
> not support the log-linear LDL hypothesis (13). In the HPS, all
> participants received 40 mg of simvastatin (the study drug) before
> randomization and investigators measured each participant's biological
> response to statin therapy. This allowed a true experimental subgroup
> analysis. By giving all study participants a brief trial of 40 mg of
> simvastatin before randomization, investigators were able to match
> control and intervention participants according to their response to
> statin therapy. Contrary to the LDL log-linear hypothesis (which would
> suggest that those who have a larger LDL cholesterol response from a
> given statin dose would receive greater benefit), those with the worst
> prerandomization LDL response (<38% reduction in LDL cholesterol
> level) received the same benefit as those with the best LDL response
> (>48% reduction in LDL cholesterol level) (Figure 2). Therefore, we
> could find no experimental evidence suggesting that the degree of LDL
> cholesterol reduction is an independent predictor of cardiovascular
> risk if LDL cholesterol level is less than 3.36 mmol/L (<130 mg/dL)
> (13). ''

> AS for high doses........." but current clinical evidence does not
> demonstrate that titrating lipid therapy to achieve proposed low LDL
> cholesterol levels is beneficial or safe. "

>  Thanks Vince

>> > not according to the abstract. "...current
>> >  clinical evidence does not demonstrate that titrating lipid therapy
>> >  to achieve proposed low LDL cholesterol levels is beneficial or
>> > safe."- Hide quoted text -

>> This article looks at several issues . The {*filter*}pin that guides all
>> statin treatment is questioned all from cited article.........
>> "In 2004, a National Cholesterol Education Program (NCEP) expert panel
>> recommended that physicians titrate lipid therapy to reach a low-
>> density lipoprotein (LDL) cholesterol level less than 1.81 mmol/L (<70
>> mg/dL) in patients at very high risk for cardiovascular events (1, 2).
>> The panel stated that consistent and compelling evidence showed a
>> strong relationship between LDL cholesterol level and cardiovascular
>> outcomes down to this level (1, 2). However, others have reviewed the
>> same literature and have concluded that there is no valid evidence
>> from clinical trials (see Glossary) supporting this
>> conclusion ........."  and looked at the reliability of TC as a
>> predictior of risk......"These results raised questions about whether
>> the strong association found at higher levels of LDL cholesterol could
>> be extended to lower LDL cholesterol levels; they also raised concerns
>> that total LDL cholesterol is an unreliable marker of benefit and may
>> be confounded by dietary factors or LDL subparticles that are the true
>> causal factors (7-11). .........

>> It also questions  one of the  prime rational behind statin guidelines

>> "The experts from the NCEP stated the following:

>> Recent clinical trials nonetheless have documented ... that for every
>> 1% reduction in LDL-C [low-density lipoprotein cholesterol] levels,
>> relative risk for major CHD [coronary heart disease] events is reduced
>> by approximately 1%. HPS [Heart Protection Study] data suggest that
>> this relationship holds for LDL-C levels even below 100 mg/dL [2.59
>> mmol/L].'......

>> And noted the lack of evidence for that statement .......

>> " Almost all published clinical trials examined fixed doses of statins
>> (placebo vs. statin or low-dose vs. high-dose statins), and no
>> published trial examined titrating lipid therapy to the proposed LDL
>> cholesterol goals. Therefore, the main results of these trials could
>> not be used to support or refute the benefits of titrating lipid
>> therapy to try to achieve these LDL cholesterol targets. We found only
>> 1 valid experimental subgroup analysis of this question, which does
>> not support the log-linear LDL hypothesis (13). In the HPS, all
>> participants received 40 mg of simvastatin (the study drug) before
>> randomization and investigators measured each participant's biological
>> response to statin therapy. This allowed a true experimental subgroup
>> analysis. By giving all study participants a brief trial of 40 mg of
>> simvastatin before randomization, investigators were able to match
>> control and intervention participants according to their response to
>> statin therapy. Contrary to the LDL log-linear hypothesis (which would
>> suggest that those who have a larger LDL cholesterol response from a
>> given statin dose would receive greater benefit), those with the worst
>> prerandomization LDL response (<38% reduction in LDL cholesterol
>> level) received the same benefit as those with the best LDL response
>> (>48% reduction in LDL cholesterol level) (Figure 2). Therefore, we
>> could find no experimental evidence suggesting that the degree of LDL
>> cholesterol reduction is an independent predictor of cardiovascular
>> risk if LDL cholesterol level is less than 3.36 mmol/L (<130 mg/dL)
>> (13). ''

>> AS for high doses........." but current clinical evidence does not
>> demonstrate that titrating lipid therapy to achieve proposed low LDL
>> cholesterol levels is beneficial or safe. "

>>  Thanks Vince

> ....HIGH RISK----not universal useage. are tyoiu reading the same
> abstract, or cherry picking the sentences you wish to reinforce,
> listener????