Friday, July 20, 2012

10 things I learned from the 46th Malaysia-Singapore Congress of Medicine

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)

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.

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.

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.

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.

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).

1. Management of Type 2 Diabetes 2009 - Malaysian CPG. 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.

The image is taken from Cleveland Clinic Journal of Medicine at URL for educational purpose only

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. 

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.

Barker DJ. Fetal origins of coronary heart disease. BMJ. 1995 Jul 15;311(6998):171-4.

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