Has your heart got the guts? dr tom mabin franschoek

Global Mortality 2000: Impact of Health Risk Factors High BP Tobacco High cholesterol Underweight Unsafe sex High BMI Physical inactivity Developing region Developed region This slide highlights the contribution of some of the leading health risk factors to global mortality, e.g. high BP, tobacco use, high cholesterol, and under-nutrition. In both developed and developing regions, high BP was among the major causes of disease burden and a leading cause of global mortality. Intensive strategies to target leading global health risk factors such as hypertension are therefore necessary. Reference Ezzati M, et al. Selected major risk factors and global and regional burden of disease. Lancet 2002;360:1347–60. Alcohol 1 2 3 4 5 6 7 8 Attributable mortality in millions (total: 55,861,000) Ezzati et al. Lancet 2002;360:1347–60

Rate of obesity rising:57% Increase diabetes mellitus 40% Europe:2005-2015 Rate of obesity rising:57% Increase diabetes mellitus 40% Smoking constant:18% Physical activity constant: 45% BP above target Lipid levels 33% above target (prev 55%)

Proven Mortality Benefits In Lowering LDL A 28 % Reduction in LDL-C significantly reduces cardiovascular events Major corronary events Coronary deaths Cardiovascular deaths All-cause deaths Per cent proportional risk reduction -31 % -29 % -27 % -21 % -35 -30 -25 -20 -15 -10 -5 LaRosa et al, JAMA 1999; 282: 2340-2346

The endothelium…miles and miles of “silk stocking”……………

How atherosclerosis develops Cholesterol penetrates inflammed artery to form plaque Platelets stick to plaque

Plaque rupture STEMI NON-STEMI Without occlusion With occlusion ACS describes the clinical manifestations of disruption of cornary arterial plaque complicated by intraluminal thrombosis and distal embolisation. Distal embolisation results in a small troponin rise, which can predict serious proximal “hot” plaque/stenosis. Without occlusion With occlusion STEMI NON-STEMI

Balloons and stents Highly successful Beneficial in short term Can recur Disease continues Not treating the underlying problem… Major questions remain………..

High cholesterol high blood pressure smoker diabetic The paradox……… High cholesterol high blood pressure smoker diabetic

The paradox….. Medium cholesterol Normal BP Not diabetic Etc etc

The paradox puzzle

“I would lie for you…and that’s the truth” Meatloaf… 1995

1980’s >500,000 patients with DU Most required surgery Helicobacter pylori bacteria implicated Cured with antibiotic No more surgery!! DNA footprint and new genetic technology can identify many more bacteria

Gut Microbiotica >135,000 species of bacteria Plus fungi,protoplasms Assist indigestible food Protect gut lining but can be triggered to cause inflammation Inflammed gut lining leaks bacterial metabolites which spread to various body organs eg arteries.

Plaque and gut bacteria DNA and genetic analysis of specific gut bacteria and plaque show similar metabolites A metabolite strongly related to atheromatous plaque is trimethylamine oxidase TMAO

TMAO Patients with history of CV events had higher TMAO levels that those who did not. Elevates TMAO levels had 3-4x higher mortality risk Elevated TMAO levels had increased risk of heart failure Ingestion of carnitene elevates TMAO and cholesterol

TMAO highl TMAO low TMAO high

Carnitine Nutrient found in all meat products Consumption causes a rise in TMAO Meat eaters have higher TMAO than vegeterians TMAO associated with raised CVD risk

TMAO TMAO = predictive risk factor for CVD Associated with specific gut bacterial populations Can be reduced by specific antiobiotics Can be reduced by specific yogurt cultures Can be reduced by specific foods (eg mediterranean)

Dietary components and CVD

DIETS: long term failures…. Seldom > 6 months in RT Unpalatable: sugar and spice Expensive Unavailable successful at weight loss but no survival benefit

the U curve……….. Low protein Low carbs Vegan Banting Atkins

The Mediteranian”lifestyle” > 4 year compliance Palatable(olive oil&nuts) Obtainable Weight loss Survival benefit =raised TMAO Expensive

Can we expect to treat CVD by manipulating the gut microbiotica by diet or medication? Stool analysis will once again become crucial. Stool transplants?....................... …..and is it true then that the way to a man’s heart is indeed through his stomach?

THANKYOU!!