By Dr AZANI MOHAMED DAUD
An obese man in his 40s is stressed at work. He smokes heavily and does not exercise. Being single, he eats out every meal.
One day, he does not turn up for work and his office colleagues assume he is attending a two-day course outside of the office. On the third day of his absence from work, his colleagues are unable to contact him and eventually break into his apartment only to find him dead. The postmortem revealed he died of a heart attack.
This story was related to me by my patient who was his office colleague. The man had become another statistic for the number one killer in Malaysia.
Heart attacks are a major cause of death in Malaysia. Although in some developed Western countries, heart attack rates have shown a decline, this is not the case in Malaysia. Furthermore, the average age of patients experiencing heart attacks in Malaysia is lower than in Western countries.
A heart attack occurs when a cholesterol plaque within the coronary arteries either ruptures or erodes, and induces the formation of a blood clot within the artery, resulting in complete obstruction of the vessel and total cessation of blood flow. The tissue downstream of the obstruction stops receiving oxygen and nutrients, resulting in death of the tissue.
Preventing heart attacks involves living a healthy lifestyle with a proper diet and adequate exercise, thereby preventing obesity, which in turn leads to diabetes and hypertension.
Complete avoidance of smoking tobacco is crucial as smoking even one cigarette a day can triple your risk of a heart attack. Do bear in mind that secondary smoking can be just as bad if not worse. Alcohol consumption, if any, should be moderate.
Recently, there has been on-going controversy regarding the importance of cholesterol, and particularly, the use of statins in preventing heart attacks. There have been discussions on websites and social media platforms, and even videos on YouTube fuelling this controversy.
Statins And Cholesterol
In the early 1960s, data from the landmark Framingham study began identifying risk factors for coronary heart disease including – amongst others – obesity, hypertension, smoking and elevated cholesterol levels, as risk factors to the subsequent development of cardiovascular disease.
Before the advent of statins, other drugs were used to lower cholesterol levels, including bile acid sequesterants and fibrates, but there were no outcome studies to show that using such agents to lower cholesterol resulted in lower death and heart attack rates. Non-drug methods have been utilised, too.
The Programme On Surgical Control of Hyperlipidaemas (POSCH) study examined whether partial ileal bypass surgery (where surgery is performed on the small intestine to allow food contents to bypass parts of the small intestine, hence reducing absorption of cholesterol and fats), together with dietary modification, was effective in lowering cholesterol and cardiovascular events when compared to dietary modification alone in patients who had survived their first heart attack.
LDL-cholesterol (LDL-C) levels was reduced by 38% in the ileal bypass group, but overall death rates or deaths due to coronary heart disease were not significantly reduced at the end of the study period of five years.
However, a subsequent analysis done five years later did show that overall death rates, death from coronary heart disease, as well as occurrence of a second heart attack, were all significantly reduced. This proved that lowering LDL-C levels by non-drug means would provide cardiovascular benefits, but took 10 years to be realised.
Statins inhibit an enzyme necessary in one of the steps of cholesterol production in the liver. Although they vary in intensity, statins can reduce LDL-C levels by up to 50%.
The first major statin study was called 4S (Scandinavian Simvastatin Survival Study). In this study, simvastatin, in addition to diet, was compared to diet alone in patients with coronary artery disease. Over the study period of 5.4 years, there was a 35% reduction in LDL-C levels translating into a 30% reduction in risk of overall death and a 42% reduction in risk of coronary death.
Since then, many studies using different statins have shown that they are all effective in reducing LDL-C and reducing cardiovascular event rates. The statin trials in general showed clear cardiovascular benefits at five years, but in the POSCH study, the cardiovascular benefits were only apparent after 10 years despite similar reductions in LDL-C levels.
Could it be that statins have other additional effects that result in these cardiovascular benefits being seen earlier?
Inflammation, The New Target?
More than 100 years ago, it was already noted by Virchow that atherosclerosis was an inflammatory process. However, for many years, it was thought that the atheroma or plaques were a passive lipid deposition causing narrowing of the vessels.
The advent of biomarkers of inflammation such as highly sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6), amongst others, which rises during inflammation, has enabled research into the role of inflammation in atherosclerosis.
Higher hsCRP levels are associated with higher cardiovascular risk and event rates, even more so than LDL-C. People with high hsCRP levels and low LDL-C levels are more likely to have a cardiovascular event than those with high LDL-C levels, but lower hsCRP levels.
The challenge till now has been to prove that by reducing inflammation per se, there will be a reduction in risk of cardiovascular events as until very recently, there were few readily available agents that targeted appropriate inflammatory pathways known to be important in atherosclerosis.
In the recently published CANTOS study, canakinumab, a human monoclonal antibody directed against interleukin-1B, a pro-inflammatory cytokine was shown to reduce hsCRP levels by 39%, which translated into a 15% reduction in cardiac events.
Canakinumab has no LDL-C lowering effect, proving that reducing the inflammatory process without lowering LDL-C improves cardiovascular outcomes.
The JUPITER study looked to see whether patients without evidence of coronary heart disease and LDL-C levels of below 3.2 mmol/L (where statins would not be prescribed), but with elevated hsCRP levels, would benefit from being treated with a statin.
The study was terminated early as an interim analysis of the data showed that the patients treated with the statin had a reduction in risk of a cardiac event of 44%, making it unethical to continue the study.
Patients whose hsCRP levels were reduced to below 2.0, but LDL-C levels remained above 1.8 mmol/L, did better than those whose LDL-C levels fell below 1.8 mmol/L, but hsCRP levels remained above 2.0, implying that inflammation is a more important parameter than LDL-C levels per se.
On a personal note, 20 years ago, I was obese, pre-diabetic, sedentary and had allowed work to consume my life. I started exercising regularly, ate healthily, tried to strike a better work-life balance and started taking statins despite my LDL-C being 3.2 mmol/L.
What about side-effects? I do get muscle aches, but it doesn’t presently stop me cycling 25km daily and up to a 100km at weekends. My kidneys and liver are fine. I haven’t developed diabetes, in fact I am no longer even pre-diabetic. I am more than 30kg lighter.
Would I stop the statin? No, I don’t want to be another statistic.
Fit For Life 2017 Penang
For more information about health, please log on to livegreat.greateasternlife.com/my.
You can also visit the FitForLife Penang 2017 fair next month for more healthy living tips. The fair’s theme “Get Fit. Live Great!” aims to inspire Malaysians to lead a healthy lifestyle and adopt a holistic approach to health that includes physical and mental fitness, financial health and general well-being. The event will feature a diverse range of health and lifestyle products and services under one roof, catering to people of all ages. Visitors can expect an array of products suitable for various health needs, such as supplements, diet and nutrition aids, health checks, alternative remedies and many others.
Dr Azani Mohamed Daud is a consultant cardiologist at Gleneagles Kuala Lumpur. This article is brought to you by Great Eastern Life. Star FitForLife Penang 2017 with the theme “Get Fit. Live Great!” is to inspire Malaysians to lead a healthy lifestyle by being physically and mentally fit. Star FitForLife Penang 2017 is organised by Star Media Group Berhad with Great Eastern Life as exclusive event partner. Nestlé Omega Plus is the official wellness sponsor.
The fair will be held in Spice Arena (PISA), Penang from Nov 17-19. It is open from 10am-7pm and admission is free. For enquiries, call 03-79671388 (ext 1529/1243/1466) or visit us at facebook.com/starhealthfair.