Heart disease is obviously one of the most serious health issues in the UK and it is very much a disease where prevention is better than cure. The opening days of 2011 will see the start of initial trials of a polypill containing three different drugs designed to minimise the risk of heart disease in over-55s. The theory of this pill, which is the idea of Professors Sir Nicholas Ward and Malcolm Law, from the Wolfson Institute of Preventive Medicine at Queen Mary, University of London, is that anyone over the age of 55 will take it daily, reducing their risk of getting heart disease. The pill contains three drugs that are commonly prescribed to combat high blood pressure and to prevent heart disease in people with a high risk of developing it; losartan, hydrochlorthiazide and amlodopine.
Losartan is an angiotensin II receptor antagonist, meaning it binds to the receptor and prevents the receptor from carrying out its normal job. The job of the angiotensin II receptors is to be part of the renin–angiotensin hormone system, which is involved in regulating blood pressure and water balance within the body. Angiotensin II, via it’s receptor, increases blood pressure in two ways; it has a direct effect on blood vessels, causing them to constrict, and it also stimulates production of a hormone, aldosterone, which acts on the kidneys to increase the reabsorption of water into the bloodstream, increasing the amount of fluid in the body, which as you can imagine, also increases the blood pressure.
Losartan acts to lower blood pressure by binding to the angiotensin II receptor, meaning that angiotensin II can’t bind and raise blood pressure. A 2009 study by Ariela Benigni and colleagues demonstrated that blocking the angiotensin II receptor can prolong the lifespan of mice, their statistics show a 26% longer lifespan when the gene producing the receptor was knocked out. As an antagonist for AT1, Losartan blocks the action of the receptor, in effect turning it off.
Hydrochlorthiazide is a type of drug known as a diuretic, which is a drug that inhibits the kidney’s ability to retain water, essentially it makes you wee. Getting rid of water lowers the amount of fluid in the body and this lowers the blood pressure. Thiazide diuretics, like hydrochlorthiazide, stop the kidney from reabsorbing sodium and chloride by inhibiting a transport protein called the sodium-chloride symporter. This also prevents water from being reabsorbed by osmosis, because the sodium and chloride ions would usually create a region of low water potential, meaning that water would rush across the membrane and into the bloodstream. When sodium and chloride don’t cross the membrane, water won’t cross either. Water is something of a sheep when it comes to crossing membranes.
The final drug in the polypill, amlodopine, is a calcium channel blocker and it acts to relax smooth muscle in the walls of arteries, which reduces blood pressure and increases blood flow around the body. Muscle contraction can only occur if calcium can enter muscle cells, because calcium triggers the muscle protein myosin to start contraction, so if the protein channel that usually opens and allows calcium to enter the muscle cell when it wants to contract is blocked, the muscle is unable to contract. And if a muscle can’t contract then it is pretty much forced to be relaxed.
That is how the pill works, by combining low doses of three pills that work together to reduce blood pressure. And all three of these drugs are relatively cheap and easy to produce. But is this really the best way for us to decrease heart disease? I suspect there is a chance that people will consider this pill as a license for them to pay less attention to maintaining a healthy diet and lifestyle, assuming that the preventative powers of the polypill will counteract the negative effects of an unhealthy lifestyle. On the other hand, is expecting people to choose a healthy lifestyle as unrealistic as expecting them to practice celibacy rather than take a contraceptive pill? Or is that not the point either? There is a strong genetic element to heart disease and people with a genetic predisposition towards heart disease may well benefit from the polypill.
Ultimately, the results of the clinical trials will give a good indication of how effective the polypill will be, but another interesting issue is how important it might be to maintain a healthy lifestyle alongside the pill. Of course it will hopefully go without saying that the pill will be more effective for someone who also maintains a healthy balanced diet and exercise regime, what remains to be seen is whether the difference in effectiveness will be enough to stop people treating this polypill as a magic heart disease drug and encourage them to treat it instead as an aid to a healthier lifestyle.