Sunday, March 11, 2012

Cardiovascular Disease and Booze!!!

We've all heard this encouragement to monitor our heart health in order to survive, and it's no new news that red wine and its famous antioxidants help protect your heart. But did you know it's not just the antioxidants, it's the alcohol itself. That's right, ethanol helps your heart. Granted its only at moderate consumption levels, but none the less, we have evidence that suggests drinking can actually protect your life, not destroy it. But before we get into that, let's actually figure out what all this hoopla about heart health is.

Yes even Burnett's can protect your heart, although it still tastes like regret.
So the primary killer of people in the world, yes that's right the world, is Cardiovascular Disease. Okay, that's kind of cheating because Cardiovascular Disease includes everything from heart attacks, strokes,  aneurysms, hypertension, congestive heart failure, and a slew of other terrible things. But let's focus just on Heart Disease, or heart attacks. This is still the number one killer of the United States and other countries, and as more countries become more developed, the number of deaths due to Heart Disease is rising, and rising fast. In fact, in the US, heart disease is responsible for 1 out of every 4 deaths! So on a macro level, this disease is a major contributor to the human death rate! Understanding this can help us model how our population is growing, and the future of this world. But funnily enough, we can also use population dynamics to understand heart disease at a micro scale. But first lets understand how it works.

Death fact: It is estimated that almost 30% of deaths this year were caused by Heart Disease

So heart disease, or commonly known as heart attacks, are a blockage of the blow flow to the heart muscle. I know this sounds weird because there is so much blood in the heart, but we have arteries that wrap around the heart and feed into the muscle which then pumps the blood around our bodies. If these arteries get blocked through some way or another, then the blood can't fuel the muscle, and the muscle cant pump. With no pump, you have no flow to the rest of your body. This causes vital organs to fail due to the lack of blood flow and death hits real quick.
So how does this happen? It's not like we have globs of gunk floating around. Relatively, our arteries are quite wide, so all the tiny proteins and nutrients we are transporting are never going to clog the artery. What does happen is Atherosclerosis. This is just a fancy way of saying your artery walls get hard due to an accumulation of cholesterol, proteins and macrophages. This accumulation happens over years and years due to an imperfect cholesterol transport system. See, in our bodies, we have two very important lipoproteins that transport cholesterol's: LDL's and HDL's. Cholesterol's are necessary for all cells in our body to ensure that the phospholipid bilayer stays fluid, and what is in the cells stays there, and stuff that is outside can only come in with the proper authorization.

Think of the cholesterol's in our phospholipid bilayer as the managers that make sure everyone else is working properly.
So we have these lipoproteins (LDL's and HDL's), which are like big sacs to move cholesterol. LDL's will bring cholesterol to all our cells and are full of cholesterol in our arteries, then are empty in our veins. HDL's are like empty sacs, that go around and pick up old cholesterol and bring them back to the liver to make bile, so we can digest and utilize new fats from our diet. This is one great circulation of maintaining balance.
Well sometimes, this messes up. The LDL's might deposit in the endothelium of our arteries, thickening the walls and messing up with our arteries. This is constantly happening because the system isn't perfect, but luckily we have our HDL's to come and mop up the mess if cholesterol is deposited in the wrong spots, say the coronary arteries (the ones that pump blood to the muscle of the heart). This buildup is called atherosclerosis. If this accumulation occurs at a faster rate than the HDL's can clean up, eventually the artery will get dangerously small, enough for something to potentially block it, like a blood clot, then BAM, heart attack!

"Now we play the waiting game, come here Mr. Clot..."

So how do we prevent the development of atherosclerosis? Simply by changing our lifestyles. By eating healthy, not smoking and exercising, we can maintain healthy arteries. Exercise stimulates Nitric Oxide release opening the arteries and promoting artery elasticity, eating right ensures the proper intake of the right amount of lipoproteins, and smoking is a vasoconstrictor (so stopping this activity reduces the chance of a blood clot or something blocking the flow). Now let's focus on diet, part of which includes alcohol intake. Recently, we've found out that by drinking just 2 drinks a day, we can also raise our HDL's. That's right, drinking responsibly actually is good for your health, and in fact can reduce your risk of heart disease by 25%!
So if we look at this scenario at the microscopic scale, we can this as an interaction between two populations, the LDL's (bad cholesterol) and HDL's (good cholesterol). HDL populations are always constant in our arteries, the only way to increase this is by changing our lifestyles. The LDL's population growth rate at the site of accumulation can be described a function that is dependent both on the amount of LDL and HDL. If the HDL's are not present, we have an accumulation of LDL's that rises exponentially. This is because as the artery constricts more and more, the chances of more LDL depositing becomes more likely. This scenario is quite similar to predator prey relationships, where if the predator (HDL) population reaches zero, we have exponential prey (LDL) growth. What we as humans try to achieve is a rate at which our HDL prevalence is at a level in which there is no accumulation of LDL's in the walls of our arteries.

At very low HDL levels, cholesterol is deposited a lot, and at advanced stages, this encourages more depositing of cholesterol. But at higher HDL levels, the cholesterol effluxes back to the liver for bile processing.
Although there are many factors that go into the development of a heart attack, this interaction is the most important. Using population ecology we can understand the interactions between these two lipoproteins. Think of the endothelium of our arteries as the habitat for these two populations, and LDL as the prey. The HDL is the predator which reduces the population of LDL in the artery. But this is where it gets interesting, if the LDL levels get too high, then the heart attack occurs, almost like the opposite of a refuge population model. The following two equations can be used to represent the populations at the site of deposit. Y represents LDL and X represents HDL. α is the chance of deposit, and β is the chance that an HDL will remove those cholesterols.

In other words, you have a high risk of accumulation of cholesterol in your arteries if the ratio of LDL to HDL is greater than 5:1. But lower is better, an ideal lipoprofile consists of LDL's lower than 100-130 mg/dl and an HDL higher than 40-60 mg/dl, or a ratio of 3.5:1. In order to change this, one must alter their lifestyle. By drinking 30 grams of alcohol (or 2 drinks a day), we can increase our blood HDL levels by 4 mg/dl. Now 4 mg/dl may seem like something quite small, but let's look at some simple examples. If you have an LDL cholesterol of 200 and HDL of 40, your ratio is 5, but by adding a mere 4 mg/dl to your HDL levels, that ratio drops to 4.5. Drinking in moderation as well as exercising can go a long way to prevent atherosclerosis, and improving both the quality and quantity of your life.

Here's a graph to help conceptualize how cholesterol is deposited over time. Age is an uncontrollable factor, and you will eventually have some deposited. But less is always better!

Overall, heart disease is a major factor in the growth rate of the human population, and the cause of this disease is primarily due to atherosclerosis, which can be thought of as predator prey relations. Hopefully, by understanding the microscopic interactions of these proteins, we can make informed decisions toward our health, and then hopefully derive medicines to mimic these mechanisms and help prevent the number one cause of death in the U.S.

For further information, check out some of these sources:
Chiuve, Stephanie E., Eric B. Rimm, Kenneth J. Mukamal, Kathryn M. Rexrode, Meir J. Stampfer, JoAnn E. Manson, and Christine M. Albert. "Light to Moderate Alcohol Consumption and Risk of Sudden Cardiac Death in Women." Heart Rhythm. 7.10 (2010): 1374-1380. Print. 
Eagon, Patricia K. "Alcoholic liver injury: Influence of gender and hormones." World Journal of Gastroenterology. 16.11 (2010): 1377-84. Print. 
Gunji T, Matsuhashi N, Sato H, Iijima K, Fujibayashi K, Okumura M, Sasabe N, Urabe A. " Alcohol consumption is inversely correlated with insulin resistance, independent of metabolic syndrome factors and fatty liver diseases." Journal of Clinical Gastroenterology. 45. (2011): 808-13.
Herrington, David M., David M. Reboussin, K. Bridget Brosnihan, Penny C. Sharp, Sally A. Shumaker, Thomas E. Snyder, Curt D. Furberg, Glen J. Kowalchuk, Thomas D. Stuckey, William J. Rogers, David H. Givens, and David Waters. "Effects of Estrogen Replacement on the Progression of Coronary-Artery Atherosclerosis." The New England Journal of Medicine. 343. (2000): 522-529. Print.
Howie, Erin K., Xuemei Sui, Duck-chul Lee, Steven P. Hooker, James R. Hebert, and Steven N. Blair. "Alcohol Consumption and Risk of All-Cause and Cardiovascular Disease Mortality in Men." Journal of Aging Research. (2011): n. page. Print. 
Jousilahti P, Vartiainen E, Tuomilehto J, Puska P. "Sex, age, cardiovascular risk factors, and coronary heart disease: a prospective follow-up study of 14 786 middle-aged men and women in Finland." Circulation. 9. (1999) 1165-72. Print.
Manson, JoAnn E., Judith Hsia, Karen C. Johnson, Jacques E. Rossouw, Annlouise R. Assaf, Norman L. Lasser, Maurizio Trevisan, Henry R. Black, Susan R. Heckbert, Robert Detrano, Ora L. Strickland, Nathan D. Wong, John R. Crouse, Evan Stein, and Mary Cushman. "Estrogen plus Progestin and the Risk of Coronary Heart Disease." The New England Journal of Medicine. 349. (2003): 523-534.
McFarlane, Samy I., Maryann Banerji and James R. Sowers. "Insulin Resistance and Cardiovascular Disease." The Journal of Clinical Endocrinology & Metabolism. 86. (2001): 713-718. Print.
Mennen, Louise I., Beverley Balkau, Sylviane Vol, Emile Cacès, Evelyn Eschwège. "Fibrinogen A Possible Link Between Alcohol Consumption and Cardiovascular Disease?" Arteriosclerosis, Thrombosis, and Vascular Biology. 19. (1999): 887-892. Print.
Mukamal, Kenneth J., and Eric B. Rimm. " Alcohol's Effects on the Risk for Coronary Heart Disease."
Odd Nilssen, Odd, Maria Averina, Tormod Brenn, Jan Brox, Alexei Kalinin and Vadim Archipovski. " Alcohol consumption and its relation to risk factors for cardiovascular disease in the north-west of Russia: the Arkhangelsk study." International Journal of Epidemiology. 34. (2005): 781-788.
Rimm, Eric B., Paige Williams, Kerry Fosher, Michael Criqui, and Meir J Stampfer. "Moderate alcohol intake and lower risk of coronary heart disease: meta­analysis of effects on lipids and haemostatic factors." British Medical Journal. 319. (1999): 1523-8. Print. 
Ronksley, Paul E., Susan E. Brien, Barbara J. Turner, Kenneth J. Mukamal, and William A. Ghali. "Association of alcohol consumption with selected cardiovascular disease outcomes: a systematic review and meta-analysis." British Medical Journal. (2011): Print. 
Sierskma, A, MS van der Gaag, C Kluft, and HFJ Hendriks. "Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels; a randomized, diet-controlled intervention study." European Journal of Clinical Nutrition. 56. (2002): 1130-36. Web. 5 Feb. 2012. <>. 
Todaa, Noboru, Kazuhide Ayajikib. " Vascular Actions of Nitric Oxide as Affected by Exposure to Alcohol." Alcohol and Alcoholism. 45. (2010): 347-355. Print.
Wong, Amy, Qiwei Paulson, JIna Hong, Renee Stubbins, Karen Poh, Emily Schrader, and Nomeli Nunez. "Alcohol promotes breast cancer cell invasion by regulating the Nm23-ITGA5 pathway." Journal of Experimental & Clinical Cancer Research. 30.75 (2011): n. page. Web. 5 Feb. 2012. <>.


  1. I'm very impressed with the idea proposed here of evaluating the relationship between HDLs and LDLs in our bloodstream as a predator-prey relationship. This blog explains this idea and its implications quite clearly. It would be interesting to see this same approach applied to the other mechanisms that might heighten the amount of HDLs in the bloodstream.

    I must admit I was extremely skeptical of this link between moderate consumption of alcohol and lower rates of cardiovascular disease mortality. But the meta-analysis of studies conducted by Ronksley et al. (2011) and cited here is quite thorough and persuasive. However, I found that the discussion of the sensitivity analysis in the paper to be confusing and insufficient. Ronksely et al. (2011) state that "Sensitivity analyses that were confined to only studies that controlled for the important confounders of smoking, age and sex revealed generally similar outcomes." This statement is clear and suggests a strong link of risk reduction with moderat alcohol consumption, but the authors further explanation about the number of confounding factors in studies is less clear (this blog here is much more clearly written!). It seems to me that this issue of confounding factors is critically important and the authors do not seem to include diet explicitly in their analysis of confounding factors. We have heard that a "Mediterranean diet" leads to lower risk of heart disease and it is in these same countries where alcohol is regularly consumed in moderate proportions. Is the lower risk due to the alcohol or all that olive oil or the entire mix of diet.

    Recommending moderate alcohol consumption as a means of reducing heart disease seems highly problematic. Most "medicines" are not mood altering and addiction is not an inherit risk. Most people do not drink or avoid alcohol for it's health benefits. They drink because of how it makes them feel (and/or for the taste). It seems highly unlikely that people will drink more or less based upon these medical associations. Rather, these medical associations seem more likely to be used simply to justify existing drinking patterns. A heavy drinker is unlikely to moderate his consumption because, "Hey, there are risks to heavy drinking, but if I drink moderately I can lower my rate of heart disease! That seems like a good compromise." Someone who drinks moderately seems likely to continue to do so. And someone who doesn't drink at all probably has some mental or emotional resistance to doing so (or simply doesn't like the taste) and is unlikely to increase their consumption to moderate levels in order to reduce their heart disease risk. In fact, it seems quite risky to "prescribe" moderate drinking to those who drink only lightly or not at all, because there is no way of knowing how enhanced consumption of alcohol will influence them. Even with moderate consumption, it seems that if that consumption becomes regular, there is the potential for dependency to develop and the level of consumption to increase with dependency.

    I am not an expert on this and I may be somewhat biased in this case: my immediate family is characterized by low alcohol consumption, but my extended family has experienced the tragedy of two different individuals who appeared to be normal on the outside while they were, in fact, high functioning addicts who slowly drank themselves to death through alcohol poisoning. I do not take the risks lightly.

  2. Continued thoughts...

    We know that diet has a significant effect on cardiovascular disease and a good diet has many other health benefits with few or no risks. While the analysis of cardiovascular disease and alcohol by Ronskley et al (2011) is thorough and persuasive in detecting a link between moderate alcohol consumption and reduced risk of heart disease, they do not sufficiently explore the confounding factor of diet and they do not provide comparative statistics between reductions in heart disease due to diet versus those due to moderate alcohol consumption. If the former (diet) has similar associations with reduced risk but carries none of the risk, it should be recommended such that the idea of moderate alcohol consumption to reduce risks may simply be a distraction from the most risk-free means of reducing hear disease risk.

    In any case, this blog does an excellent job of walking the reader through these issues and explaining the relationship between HDLs and LDLs and their link to heart disease with the effective analogy of predator-prey relationships. I'd like to see this analysis applied to other mechanisms of increasing HDLs.

    1. I understand the caution you have toward these links, but know that these are links tied to deaths by Cardiovascular Disease, not just all risk mortality. In fact, the more you drink, the less likely you are to die of cardiovascular disease, but the risk of dying to other diseases, such as liver failure, skyrocket. The efforts of these studies are meant for those who are struggling with the battle for preventing Cardiovascular Disease. Genetics, age, and sex, these uncontrollable factors, play a huge role in determining your lipoprofile and ability to combat the onset of atherosclerosis, and sometimes those who are exercising regularly and maintaining a healthy diet still show signs of atherosclerosis. Drinking represents that last ditch effort to prevent CVD. Its the straw that will break the camel's back; and as you state, not something that we should actively pursue from the beginning.