the nutrition prevention and reversal of cardiovascular disease: fact or fiction? caldwell b....
TRANSCRIPT
![Page 1: The Nutrition Prevention and Reversal of Cardiovascular Disease: Fact or Fiction? Caldwell B. Esselstyn, Jr., MD](https://reader036.vdocuments.mx/reader036/viewer/2022062304/56649d755503460f94a565cd/html5/thumbnails/1.jpg)
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The Nutrition Prevention and Reversal of Cardiovascular Disease: Fact or
Fiction?Caldwell B. Esselstyn, Jr., MD
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Highlights
• The world’s advanced countries have easy access to plentiful high fat
food; ironically, it is this rich diet that produces atherosclerosis
• In the world’s poorer nations, many people subsist on a primarily plant-
based diet, which is far healthier, especially in terms of heart disease
• The time is long overdue to offer cardiovascular disease patients
treatment for the causation of their disease
• The present standard cardiology approach cannot cure patients, nor halt
disease development, and is financially unsustainable
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Highlights• All patients in a non-emergency situation should be offered the option of plant-
based nutrition to halt and reverse their disease by practitioners who are
knowledgeable with this approach
• Nutritional intervention, as shown in our study and others, has halted and even
reversed CAD
• The safety, diminished expense, and prompt, powerful, and persistent results in
treating the cause of vascular disease by whole-food plant-based nutrition offer
a paradigm shift from existing practice
• Arrest and Reversal outcomes with Diet
- No mortality
- No morbidity
- Benefits improve with time
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Update on PCSK9 Inhibitors and New Therapies
Evan A. Stein, MD
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Highlights• Elevated low-density lipoprotein cholesterol (LDLC) levels in the plasma is the
most important causative factor of atherosclerosis and associated ischemic
cardiovascular diseases
• The LDL receptor (LDLR) is the preferential pathway through which LDLs are
cleared from the circulation
• LDLs bound to the LDLR are internalized into clathrin-coated pits and
subsequently undergo lysosomal degradation, whereas the LDLR is recycled
back to the plasma membrane
• Circulating PCSK9 binds the LDLR on the cell surface and is subsequently
cointernalized together with the LDLR
• This promotes the degradation of the receptor in the lysosome, rather than
recycling to the plasma membrane. PCSK9 can also bind the LDLR intracellularly
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Highlights• By virtue of its role as a major inhibitor of the LDLR, PCSK9 has emerged
as a hot new drug target to treat hypercholesterolemia and coronary
heart disease
• ODYSSEY, OSLER 1 & 2 trials have demonstrated that alirocumab and
evolucumab decrease LDL by ~60% and CVD events by ~50% at 12-18
months
• PCSK9 is a promising option for patients truly statin intolerant (or who
don’t have adequate LDL lowering despite statin therapy)
• But long term safety is still unknown and final CVD outcomes data
pending
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New Treatments for Hypercholesterolemia: Apheresis, Mipomersen, Lomitapide & PCSK9
Inhibitors
James M Falco
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Highlights• Apheresis has an important role in the management of two common
complex lipid disorders associated with a high risk of premature
atherosclerotic disease, familial hypercholesterolemia (FH) and Lp(a)
hyperlipidemia
• LDL apheresis is indicated in patients with LDL > 200 mg/dl with CHD,
asymptomatic patients with LDL >300 mg/dl and in selected CHD
patients with LDL >130 mg/dl with Lp(a) > 50-60 mg/dl
• Studies have shown significant reductions of CV event stabilization
and/or improvement of lesions and overall CV survival
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Highlights• Mipomersen is a second generation antisense oligonucleotide that
targets apolipoprotein B
• Mipomersen reduces all apolipoprotein B containing atherogenic
particles and displays dose dependent reductions between 50-400
mg/week both as a single agent and in the presence of maximal lipid
lowering therapy
• Mipomersen is rapidly and extensively absorbed after subcutaneous
administration and has an elimination half-life of approximately 30
days across species
• No drug-drug interactions have been identified with Mipomersen
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Highlights• Lomitapide is a microsomal transfer protein inhibitor indicated as an
adjunct to low fat diet and other lipid lowering therapies
• It reduces LDL, total cholesterol, apo B and HDl cholesterol in patients
with homozygous familial hypercholesterolemia (HoFH)
• Inhibitors of proprotein convertase subtilisin kexin type 9 (PCSK9)
represent a new therapeutic category of drugs for the treatment of
dyslipidemia and atherosclerotic cardiovascular disease
• Drugs which negate the action of PCSK9 can produce substantial
reductions in atherogenic lipoprotein cholesterol-carrying particles and
thereby hold the potential for further reducing events associated with
atherosclerotic cardiovascular disease
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Statin Intolerance: Statin Side-Effects?
Lisa Tannock, MD
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Highlights• In clinical practice 10-25% of patients report statin associated muscle
symptoms (SAMS) or intolerance like Myalgia, myopathy and
rhabdomyolysis
• Patient related factors that can increase the risk of statin induced
myopathy include: increasing age, female sex, renal insufficiency,
hepatic dysfunction, hypothyroidism, diet (i.e grapefruit juice) and
polypharmacy
• The properties of statins that can increase the risk of statin induced
myopathy include: high systemic exposure, lipophilicity, high
bioavailability, limited protein binding, potential for drug-drug
interactions metabolized by CYP pathways (particularly CYP450 3A4)
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Highlights• Statins may decrease LFTs that are high due to fatty liver.
• If AST/ALT < 3 times ULN, it is ok to continue statin therapy
• If muscle symptoms occur, measure CK and TSH
• CK >10 x ULN: discontinue all lipid meals. CK <10 x ULN: measure weekly, if it
is increasing discontinue medicines and if decreasing ok to continue statins
• In case of SAMS, European Atherosclerosis Society (EAS) recommends to
• Discontinue the statin and then retry
• Try at least 3 different statins
• Use maximum tolerated statin dose combined with non-statin lipid
therapies
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Advanced Lipid Testing: LDL Particles for the Clinicians
Peter Jones
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Highlights• Advanced lipid testing consisting of biomarkers which are lipid or non-lipid
parameters beyond those included in a routine lipid profile enables clinicians
to effectively measure and treat lipid abnormalities.
• Biomarkers can be useful in determining disease state, rate and trait and
helps to assess the initial ASCVD risk, before starting lipid-altering therapy but
also to monitor the progress of therapy
• Following tests which can be useful for assessing baseline risk and for on-
treatment decisions
– Evolved LDL cholesterol testing consisting of non-HDL, apoprotein B, LDL-P
– Evolved HDL cholesterol testing consisting of HDL-P, apoprotein A1
– Lipoprotein (a)
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Highlights• Basic lipid panel (preferably fasting), with LDL and non HDL is required.
A nonfasting non-HDL cholesterol still be useful
• Further measures of atherogenic particle number (apo B, LDP-P) are
not necessary since non-HDL is equivalent and sufficient even in
discordant situations
• Routine measurement of Lp(a) is not needed. It can be done for
patients with a personal history of premature CVD, a family history of
premature CVD, or familial hypercholesterolemia.
• A high risk level for Lp(a) is >50 mg/dl
• Lipid particle size and/or density is not helpful if the overall particle
number is known
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Triglyceride Lowering Agents: Should they be used outside Lipid clinic?
Eliot Brinton
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Highlights• Mendelian randomization data strongly suggest that
hypertriglyceridemia (HTG) causes atherosclerotic cardiovascular
disease (ASCVD)
• Hence, triglyceride (TG) lowering treatment in HTG is now more
strongly recommended to address the residual ASCVD risk than
has been the case in earlier published guidelines
• Fasting TG measurement is standard. Non-fasting TG predicts
CVD risk in populations but is too variable in individuals
• If non-fasting TG <200 mg/dl, fasting TG is not necessary.
Remnant particle testing is controversial
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Highlights• Statins are the best-established agents for ASCVD prevention,
and so are usually used as first-line treatment of TG levels less
than 500 mg/dL
• Statin monotherapy may fail to normalize high triglycerides and
low high-density lipoprotein cholesterol, and it prevents only a
minority of CVD events
• Fibrates are the best-established agents for TG level lowering
and are generally used as first-line treatment of TG levels greater
than 500 mg/dL
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Highlights• Further treatment of lipid disorders that remain after statin
monotherapy should help reduce the residual CVD risk
• Fibrate monotherapy lowers high triglyceride levels, raises low
high-density lipoprotein cholesterol, and reduces CVD risk
• Hence, fibrates are recommended as an adjunct to statins for
treatment of residual dyslipidemia and residual CVD risk
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Metformin: The Role of Its Non-Glycemic Effects in Cardiovascular Risk Reduction
John Miles, MD
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Highlights• Metformin has proven itself as a front runner in the therapeutic
armamentarium of type 2 diabetes and various other metabolic
diseases
• Metformin exerts most varied effects on both large and small
vessels, as well as on haemostatic parameters
• Metformin has remarkable and partly unique properties in the
microcirculation, which can largely explain its long-term
superiority in the UKPDS trial
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Highlights• Metformin has been associated with less CV morbidity and
mortality, at least in part independently of improvement in
glycaemic control and other risk factors, such as hypertension,
obesity and dyslipidaemia
• Metformin use has been associated with reduced mortality in
patients with diabetes and heart failure
• Metformin has demonstrated beneficial effects on systolic BP,
heart rate, LV mass, stroke volume, cardiac index and cardiac
work
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Dual-acting Saroglitazar effective for diabetic dyslipidemia with fewer side effects
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Highlights• In a 9-month, postmarketing study among Indians, Saroglitazar
was well tolerated and effective in diabetes patients whose
dyslipidemia was not controlled by statins
• The 9-month study included 787 patients in India with diabetic
dyslipidemia treated with 4 mg daily of Saroglitazar
• Glycemic parameters were evaluated at baseline and at 3
months, 6 months, and 9 months. At 9-month follow-up:
- Triglyceride levels were reduced by 43.8%
- LDL cholesterol was reduced by 18.5%
- Total cholesterol was reduced by 23.1%
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Highlights• A significant improvement was seen in HDL cholesterol, which
rose from 41.0 ± 14.73 mg/ dL at baseline to 44.5 ± 8.31 mg/dL
• HbA1C dropped from 8.5 ± 1.37% to 7.0 ± 0.78% at 9-month
follow-up (P<0.0001), and fasting and postprandial blood sugar
were also significantly reduced at 9-month follow-up by 28.1%
and 35.2% (P<0.0001) respectively
• Treatment with the drug was not found to be associated with an
increase in body weight (73.9 ± 11.92 kg at baseline to 72.4 ±
11.55 kg at 9-month follow-up) and there were no reports of
serious adverse events among users
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Insulin pump therapy superior to multiple daily injections for HbA1c levels
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Highlights• Lee and colleagues conducted a run-in period for the OpT2mise trial for
dose optimization on 495 individuals with poor glycemic control on
multiple daily injections
• Following the run-in phase, 331 participants with HbA1c levels of 8% to
12% either continued multiple daily injections (n = 163) or switched to
pump therapy (n = 168) for 6 months to compare the two treatment
types
• After 6 months, HbA1c levels decreased by 1.1% in the pump therapy
group and by 0.4% in the multiple daily injections group (P < .001)
• Compared with participants in the injections group, participants in the
pump therapy group were more likely to achieve HbA1c levels below
8% (P < .001)
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Highlights• Total daily insulin doses were greater in the injections group (122 U)
compared with the pump therapy group (97 U) after 6 months (P
< .0001)
• The pump therapy group had significantly lower 24-hour sensor
glucose values at 6 months compared with the injections group (P
< .05) after comparing results to the first CGM study
• The pump therapy group also spent fewer minutes per day in
hyperglycemia compared with the injections group (P < .001)
• Improved treatment satisfaction was significantly associated with
greater HbA1c reductions at 6 months for the pump therapy group but
not the injections group (P < .05)
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Analysing Endothelial Dysfunction In Type2 Diabetes Mellitus Patients Using Flow Mediated
Dilatation Score
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Highlights• A study was performed to determine early stage CVD risk in type
2 DM patient using FMD (flow mediated dilatation) score –
correlating it with acceleration of inflammatory process of
vascular injury.
• A total of 50 (36 F and 14 M) patients with type 2 DM of more
than 10 years with age above 50years were screened for FMD
score along with 30 (17 F 13 M) healthy controls, using
Angiodefender.
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Highlights• The FMD score in 50 type 2 DM patients showed that 70% (n=35)
patients suffered from impaired endothelial function and
increased arterial thickness; 16% (n=8) patients suffered from
endothelial dysfunction, arterial stiffness and atherosclerosis
whereas the remaining 14% had normal endothelial function.
• On the other hand in the healthy counterparts, the FMD score
was normal in 80% (n=24) patients.
• Flow mediated dilatation score can be effectively used as a
marker to determine the vascular injury and endothelial
dysfunction in patients with type2 DM.
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Correlation of left ventricular hypertrophy & left ventricular diastolic dysfunction with HbA1c in
newly diagnosed type 2 diabetics
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Highlights
• This study was carried out to assess the frequency of left ventricular
hypertrophy (LVH) and left ventricular diastolic dysfunction (LVDD)
in normotensive newly diagnosed type 2 diabetic patients by using
2D echocardiography and correlation with HbA1C.
• 100 newly diagnosed normotensive type 2 diabetes mellitus
patients between 30 - 60 year of age were enrolled from endocrine
OPD of a tertiary care center during a period of 1 year.
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Highlights
• Results: 41 % patients had LVDD and 37 % patients had LVH.
• The mean HbA1C of population with LVDD was 7.67 ± 0.90 % and
that with LVH was 7.74 ± 0.91 %. The LVDD and LVH were positively
correlated with HbA1C (p value = 0.0057 & p value = 0.0011)
respectively
• Left ventricular diastolic dysfunction & left ventricular hypertrophy
were positively correlated with HbA1C in newly diagnosed T2DM
population