Monday, November 3, 2008

Cardiometabolic disease


Modern lifestyle has led to a boom in the market for pharmacological and non-drug management of the so-called lifestyle diseases. Yoga evangelists like Baba Ramdev are riding on this lifestyle disease wave. Examples of lifestyle diseases include: cardiovascular disease, cancer, diabetes, obesity, and respiratory diseases like COPD, and asthma.

rdiometabolic disease refers to a combination of cardiovascular disease and metabolic dysfunction. The patients of cardiometabolic disease have cardiovascular disease and an accompanying endocrinological or metabolic disorder like diabetes. Cardiometabolic diseases are also a part of the lifestyle diseases.

Cardiovascular disease refers to diseases of the heart & blood vessels. 80% of deaths due to cardiovascular diseases occur in developing countries. In fact, 28th Sep is celebrated as World Heart Day to highlight the growing cardiovascular risks. By 2015, there will be 100% rise in deaths due to cardiac ailments in India as per WHO. In Japan in the meantime deaths due to cardiovascular diseases have decreased by 60%!

Heart attack, TIA (transient ischemic attacks), strokes and leg attack (peripheral vascular disease) are manifestations of cardiovascular disease. As per ORG IMS Sep 2008, the Indian market of cardiovascular disease management drugs is Rs. 3584.17 crores per annum and growing at 18%.

Primary prevention or leading a healthy lifestyle – is essential to reducing the cardiovascular disease burden. A daily routine of at least 10000 steps is a must for a healthy lifestyle. In fact, lack of exercise increases the body's risk of developing heart disease by 150 per cent. Quitting smoking, right management of stress, and a healthy diet are a part of healthy lifestyle.

High blood pressure – hypertension – can be reduced by supporting diuresis and vasodilation. As such, excessive calcium ions in the muscle cells of heart and blood vessels, causes increased contraction of actin and myosin (the contractile proteins). This results in excessive contractions of heart and blood vessel muscles. Hence, increased pumping of blood by the heart and increased contraction of blood vessels leads to increased cardiac output (more blood being pumped out by the heart) and vasoconstriction (blood vessels contract, decreasing the lumen of the blood vessel) respectively. This leads to increased blood pressure (ie., the lateral pressure of blood exerted on the blood vessel walls through which it is flowing).

A new approach in the clinical management of hypertension is by establishing ion-water balance across the cell membrane, and preventing entry of excessive calcium ions in to the cells, thereby reducing excessive vasoconstriction. To establish normal ion-water balance across the cells, and maintain normal cell volume the body has natural organic osmolytes. Myo-inositol and taurine are two important organic osmolytes that help in maintaining ion-water balance across the cell membrane.

Uncontrolled hypertension
leads to kidney damage (one in 10 Indians suffer kidney disease), blood vessel damage, heart attack, and congestive cardiac failure.

Obesity, diabetes, and hypertension
are the chief causes of CVS diseases. A key component of unhealthy lifestyle is SMOKING. When a cigarette is smoked, the person inhales 250 to 400 toxic chemicals (50 of them being carcinogens). The chemical poisons inhaled during cigarette smoking is known to cause endothelial dysfunction. The first stage of atherosclerosis (thickening and hardening of blood vessel walls, leading to loss of elasticity) is endothelial dysfunction (the innermost lining of blood vessels does not function normally). Smoking increases the chances of heart disease by two fold.

The world over, gastrointestinal and anti-infective pharma markets are big bucks. However, cardiometabolic disease, onco segment, and other lifestyle disease markets are growing in size rapidly.

A boost to metformin

Metformin is an oldie goldie drug in the management of diabetes. Currently, there is a school of thought gaining traction in medical circles, to make metformin the ABSOLUTE first line of therapy. The reasons are not just pharmacological; it is also about, patient compliance due to metformin's pocket friendly price.
Further, there is new and exciting information that metformin helps in reigning in mortality due to heart disease in diabetics. Now, that is powerful information. The strength of metformin is the great amount of valuable clinical experience backing it.

Metformin seems to be fated to becoming an evergreen drug in the management of diabetes (particularly Type 2), the world over.

Managing diabetic complications: 'serious stand alone markets'

In the management of cardiometabolic disease, it is not just blood sugar control, the management of diabetic complications too is emerging as serious stand alone markets for pharma marketers. There are various drugs and dietary supplements available, to effectively manage diabetic complications.

The market for managing diabetic complications is nascent and growing rapidly due to increasing consciousness of diabetes and its complications. Of the All India Pharma market which is worth Rs. 33604 crores with growth of 13%, the market for drugs used in diabetes is valued at Rs. 1756 crores and growing at 20%. . An example of a hot sub-market in the diabetes segment is the diabetic neuropathic market (disease of the nerves in diabetics). This is the hottest segment of the drug markets for diabetic complications.

Diabetic neuropathy –
it is the most common complication of diabetics. The prevalence in India is supposed to range from 19% to 28% of diabetics. The prevalence increases with age and duration of diabetes. Concomitant factors like increased blood lipid levels, smoking etc increase occurrence and intensity of diabetic neuropathy.

Signs and symptoms of
diabetic neuropathy:

  • numbness, tingling, or pain in the toes, feet, legs, hands, arms, and fingers
    wasting of the muscles of the feet or hands
    indigestion, nausea, or vomiting
    diarrhea or constipation
    dizziness or faintness due to a drop in blood pressure after standing or sitting up
    problems with urination
    erectile dysfunction in men or vaginal dryness in women
Symptoms that are not due to neuropathy, but often accompany it, include weight loss and depression.

Osmotic stress on the cell membrane is common in diabetics and hypertensives. In hyperglycaemic patients, sorbitol and reactive oxygen species levels rise leading to osmotic stress on cells. These osmotic changes lead to neuropathic pain. Organic osmolytes may have a role in helping manage neuropathy.

Methylcobalamin 1500 mcg and alpha lipoic acid 300 mg per day are useful in arresting the progression of diabetic neuropathy and its severity. (The Indian Practitioner, Oct 2008, p.nos. 621 to 628).

The kidney connection

The renal basis of hypertensive cardiovascular disease is becoming more and more evident. The importance of the kidney in hypertension, is due to the group of cells called JUXTAGLOMERULAR cells. These cells secrete an enzyme called renin. This enzyme converts angiotensinogen - a protein circulating in blood - to angiotensin 1. Angiotensinogen is produced by the liver and put in to the blood circulation.

Angiotensin 1 is then further converted in to angiotensin 2 by another enzyme angiotensin converting enzyme (ACE). Angiotensin 2 is a potent vasoconstrictor (constricts or contracts blood vessels). This increases blood pressure. Further, angiotensin 2 through its influence on a hormone called aldosterone increases absorption of water from kidneys (the water comes from the filtered blood), and shifts it back to blood. This increases blood volume. The net result: increased blood pressure.

The most popular antihypertensive drugs on the kidney system are the ACE inhibitors that inhibit activity of angiotensin converting enzyme. There are angiotensin 2 antagonists like losartan sodium, and new off-the-block drugs are renin antagonists.

The haemodynamic equation

So ultimately what do all these antihypertensive drugs do? They either decrease the vascular resistance (ie., cause blood vessels to dilate) or decrease the cardiac output (ie., blood pumped out by heart in one minute) or decrease both ie., vascular resistance and cardiac output. This is encapsulated in the haemodynamic equation:

BP (blood pressure) = PVR X CO

In this equation, PVR is the peripheral vascular resistance, which depends on the diameter of the blood vessels. The CO factor is cardiac output. This depends on the force of contraction of heart, heart rate, and the blood volume.

Antihypertensive drugs tend to decrease the heart rate, or force of contraction, or blood volume (by increasing the urine output), or cause vasodilation (increase blood vessel diameter).

The final conclusion

Cardiometabolic diseases are causing immense morbidity and mortality world wide. Developing countries are not spared nor are the developed countries safe from these diseases. Pharma marketers have donned their war gear for waging a war against cardiometabolic disease. However, they are just one front, the Govt. and NGOs need to launch massive communication exercises to create a lot of societal consciousness on cardiometabolic diseases. For eg., NACO is an organization to help fight AIDS. Similarly, we need a specialized apex body to lead the communication battle to ensure increased focus on cardiometabolic disease – a killer disease on the prowl.



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