10 things I learned from the 46th Malaysia-Singapore Congress of Medicine
Although this congress has not much relevant topics pertaining to
emergency medicine, I learned a number of things on cardiometabolic
updates. Below are some of the things I learned:
1. In a patient with STABLE coronary disease, a recent landmark trial
called the COURAGE trial shows that the nearly 5-year incidence of death
or MI was similar whether the patient undergoes PCI or optimized
medical therapy alone, although PCI showed some advantage in relieving
angina.
Reference:Boden WE, O'Rourke RA, Teo KK, Hartigan PM, Maron
DJ, Kostuk WJ, Knudtson M, Dada M, Casperson P, Harris CL, Chaitman BR,
Shaw L, Gosselin G, Nawaz S, Title LM, Gau G, Blaustein AS, Booth DC,
Bates ER, Spertus JA, Berman DS, Mancini GB, Weintraub WS. Optimal
medical therapy with or without PCI for stable coronary disease. N Engl J
Med. 2007 Apr 12;356(15):1503-16. Click
here to download the FREE FULL TEXT in pdf
2. However, in another on-going study with has to be halted prematurely (
the FAME II study),
for a specific sub-group of patients with stable coronary disease and
documented hemodynamically significant stenosis (detected from
fractional flow reserve, FFR), these patients will have a more than
10-times-higher risk of urgent revascularization if they are initially
treated with optimal medical therapy (OMT) rather than PCI.
Hence, as the coordinating clinical investigator of this trial, Dr Bernard De Bruyne, said, the findings from FAME II are
not "anti-COURAGE", but a complement or an extension of "COURAGE."
In other words, if properly selected, a patient would benefit significantly from PCI.
3. In a patient with left ventricular systolic dysfunction, CABG may
reduce the risk for cardiovascular death or revascularization, but it
does not appear to prolong life compared with contemporary
guideline-based medical therapy (no statistical significant difference
in the rate of all-cause mortality in a follow-up of up to nearly 5
years) (STICH trial)
Reference:
Velazquez EJ, Lee KL, Deja MA, Jain A, Sopko G, Marchenko A, Ali IS,
Pohost G, Gradinac S, Abraham WT, Yii M, Prabhakaran D, Szwed H,
Ferrazzi P, Petrie MC, O'Connor CM, Panchavinnin P, She L, Bonow RO,
Rankin GR, Jones RH, Rouleau JL. Coronary-artery bypass surgery in
patients with left ventricular dysfunction. N Engl J Med. Apr
28;364(17):1607-16. Click
here to download the FREE FULL TEXT in pdf
4. In a patient with homozygous familial hypercholesterolemia (FH),
with very high cholesterol level and who do not respond well to maximum
multiple drug therapy, LDL apheresis may be considered (much like renal
dialysis). Meanwhile statins have the adverse effect of elevating the
liver enzymes.
Reference:
2011 Malaysian CPG Management of Dyslipidemia (4th ed). Click
here to download the FREE FULL TEXT in pdf
5. Statins, especially in high dose, can cause derangement in liver
enzymes but ACC/AHA/NHLBI recommends that statins should be discontinued
(or lowered the dose of) if the ALT or AST are above 3 times the upper
limit of normal on 2 consecutive occasions. Nonetheless, the exact
mechanism of how statins cause elevations of ALT and
AST is still unknown.
Reference:
Pasternak RC, Smith SC, Jr., Bairey-Merz CN, Grundy SM, Cleeman JI,
Lenfant C. ACC/AHA/NHLBI Clinical Advisory on the Use and Safety of
Statins. Circulation. 2002 Aug 20;106(8):1024-8. Click
here to download the FREE FULL TEXT in pdf
6. For patient with subclinical hypothyroidism, initiate treatment if
the TSH ≥10 mIU/L. TSH levels ≥10 mIU/L associated with increased
cardiovascular morbidity and mortality.
Reference:
Weiss IA, Bloomgarden N, Frishman WH. Subclinical hypothyroidism and
cardiovascular risk: recommendations for treatment. Cardiol Rev.
Nov-Dec;19(6):291-9.
7. Overt hyperthyroidism which has been shown to be associated with
cardiac arrhythmias, hypercoagulopathy, stroke, and pulmonary embolism,
is found to be associated with a 20% increased mortality in a recent
meta-analysis.
Reference:
Brandt F, Green A, Hegedus L, Brix TH. A critical review and
meta-analysis of the association between overt hyperthyroidism and
mortality. Eur J Endocrinol. Oct;165(4):491-7. Click
here to download the FREE FULL TEXT in pdf
8. Metformin is the only oral anti-diabetic that has been proven to
reduce cardiovascular mortality in trials such as the UKPDS; and as
such, it should be continued unless the patient has been shown to have
documented a GFR reduction <30%. Metformin does not cause
hypoglycemia attack and has been shown to be weight neutral or result in
weight reduction. Lactic acidosis is a concern but only in the presence
of hepatic failure. There is, however, a question that metformin may
lead to Vit B12 deficiency over a long term use.
Thiazolidinediones, like rosiglitazone, has been shown to be associated
with an increased risk for myocardial infarction and possibly
cardiovascular mortality in a recent meta-analysis. There are also
evidence to suggest that thiazolidinediones may increase risk of bladder
cancer (
click here for an article).
Click
here to download the FREE FULL TEXT in pdf.
2. Home PD, Pocock SJ, Beck-Nielsen H, Gomis R, Hanefeld M, Jones NP,
Komajda M, McMurray JJ. Rosiglitazone evaluated for cardiovascular
outcomes--an interim analysis. N Engl J Med. 2007 Jul 5;357(1):28-38. Click
here for full text access.
9. Bariatric surgery is a useful and appropriate treatment for obese
people with type 2 diabetes NOT achieving the recommended treatment
targets with medical therapies, especially when there are other major
co-morbidities.
Diabetic patients with a BMI between 30 and 35 and cannot be adequately
controlled by optimal medical regimen and especially in the presence of
other major cardiovascular disease risk factors, may also be considered
for bariatric surgery.
There are various methods of bariatric surgery, which can be divided into
- Gastric restrictive procedures (laparoscopic adjustable gastric
banding, sleeve gastrectomy, vertical gastroplasty) limit gastric volume
and, hence, restrict the intake of calories by inducing satiety.
Gastric banding, for example, may limit the volume to only 30 ml or 2
table spoons!
- Intestinal bypass procedures (Roux-en-Y gastric bypass,
biliopancreatic diversion) also restrict caloric intake, the way gastric
banding and vertical gastroplasty do. But because the small intestine
is shortened, they have an added component of malabsorption of fat and
nutrients.
Bariatric surgery as a treatment for Type 2 diabetes is endorsed by the
International Diabetes Federation (IDF) in its position statement on
bariatric surgery.
Click here to download the statement.
However, the IDF position statement recommends only 2 procedures,
namely Roux-en-Y gastric bypass (RYGB) and laparoscopic adjustable
gastric banding (LAGB), are currently conventional bariatric surgical
procedures for adolescents.
How does bariatric surgery works? Besides limiting the volume of the
"stomach", bariatric surgery induces a number of hormonal or metabolic
changes. There are two theories behind:
- the “hindgut theory” which suggests that accelerated transit of concentrated nutrients
(particularly glucose) to the distal intestine results in increased
production of insulinotropic and
appetite-controlling substances
- the “foregut theory” which suggests that since nutrient interactions
in the duodenum are diabetogenic; through bypassing the duodenum, this
would reverse this
defect.
Reference:
Kashyap SR, Gatmaitan P, Brethauer S, Schauer P. Bariatric surgery for
type 2 diabetes: weighing the impact for obese patients. Cleve Clin J
Med. Jul;77(7):468-76. Click
here to download the FREE FULL TEXT in pdf.
10. Contrary to what many think, an infant's low birth weight and poor
nutrition can actually lead to increased prevalence of coronary heart
disease, diabetes, hypertension, stroke, etc during adult life.This is
known as the Barker hypothesis because it was first described by Barker
in an epidemiology study.
Epigenetics is the study of the heritable changes in gene expression or cellular phenotype
WITHOUT changes in the underlying DNA sequence – hence the name epi- (over, above, outer) -genetics.
It refers to functionally relevant modifications to the genome by
mechanisms such as the histone chain that wraps around the gene. The
more tightly "wrapped" the gene is, the more silenced the gene becomes.
The other mechanism is through epigenome tags such as the methyl tag.
The more methylation, the more silenced the gene becomes.
These epigenomes can interact with the environment and can "listen" to
signals from the environment. This, early-life metabolic adaptations
help in survival of the organism by selecting an appropriate trajectory
of growth in response to environmental cues.
Click here to watch a video on epigenetics.
Reference:
Barker DJ. Fetal origins of coronary heart disease. BMJ. 1995 Jul 15;311(6998):171-4.
