Cholesterol, tobacco, fatty foods, high blood pressure, stress and genes have all been implicated as smoking guns. Red wine, exercise and vegetables have been propounded as important bodyguards. But none of these completely solve the riddle. Scientists know that there's still a missing link.
That link, some now believe, could be a common respiratory infection carried by people the world over. If they are right, we could be "catching" our heart attacks, and heart disease could be halted with a course of antibiotics.
The infection is Chlamydia pneumoniae, a cold bug that's so common 60 to 70 per cent of the population are infected with it at any one time. It's spread liberally by saliva droplets and usually hits in the respiratory system causing the classic coughs, splutters and sneezes of a chest infection. We're constantly exposed to the bacterium and while sometimes antibiotics and a few days at home in bed might be needed to get over a particularly virulent attack, most of the time, scientists believed, our immune system simply deals with the repeated infections and we feel no more than a little under the weather.
But now it looks like the bug might not be so easily banished and, not only does it not go away, it migrates to cause trouble elsewhere.
In the late Eighties, researchers in Finland and the United States found people with atherosclerosis - the narrowing of the arteries which eventually stops blood from reaching the heart and causes a heart attack - had far higher levels of antibodies to C pneumoniae in their blood stream than healthy people. In 1993 South African scientists found the C pneumoniae organism in the walls of diseased sections of arteries of patients who had died from heart disease.
Then this year researchers from the University of Utah School of Medicine in the US, who were studying patients having operations to scrape plaque out of their arteries, found that two thirds of them had C pneumoniae living in the plaque and damaged sections of the artery but no evidence of the organism where the artery wall was healthy.
At the same time other researchers in both the States and Britain were finding the bug - alive and kicking - in the plaque accumulating in other parts of the cardiovascular system such as the arteries of the leg and neck.
This was a breakthrough. Just being there, of course, doesn't prove that C pneumoniae is malign - though some would argue that giving living space to any foreign bacteria is unlikely to be beneficial. But according to Dr Sandeep Gupta, a young British Heart Foundation research fellow at St George's Hospital, London, in hot pursuit of the maverick lung bug, it did raise interesting questions. Like how does it get into the artery walls, what exactly is it doing when it gets there, and what happens if you get rid of it?
Current thinking, says Dr Gupta, is that C pneumoniae hitches a ride into the arteries on the warrior cells - macrophages - of our immune system as they pass through the lung's blood system on their way around the body.
One likely destination of these macrophages will be parts of the artery walls where factors such as cholesterol and smoking have caused inflammation and injury to the wall surface. The damaged surface would make it easy for the hitch-hiking C pneumoniae to infiltrate the artery wall and set up a vicious cycle of chronic infection, he suggests.
The immune system reacts to this constant infection by sending more macrophages, which not only cause scarring and thickening of the artery walls as they scavenge inflammation cells and seek to repair the damage, but also trigger off a cascade of the very blood-clotting factors and proteins involved in forming the characteristic sludge found in the arteries of people with coronary heart disease.
This sticky grey glistening plaque narrows the arteries, restricts the blood flow and sloughs off the clots of fat and tissue that can kill if they reach the heart. It also provides perfect living conditions for C pneumoniae which, luxuriating in the fatty environment, happily continues to overstimulate the immune system and stoke the production of more plaque.
C pneumoniae's apparent ability to trigger scarring plaque production squares with the effect of its very close relation, Chlamydia trachomatis, a pathogen that causes a sexually transmitted disease characterised by scarring of the Fallopian tubes, and is the biggest cause of eye damage in the developing world.
But the only way now to find out if the theory really holds water is to get rid of the bug and watch the result. Which is exactly what Dr Gupta and his colleagues from the cardiology, haematology and virology departments of St Georges Hospital are doing.
Sixty men who have recently had heart attacks have been recruited to the first ever study of antibiotic eradication therapy for atherosclerosis. Thirty have been given a three-day course of an antibiotic which is commonly used to fight respiratory infections. The remaining 30 have, unbeknown to them, taken a placebo course.
The key is to find out what happens to the substances in the blood that signal the presence of infection and immune-system response, such as the clotting factor fibrinogen, monocyte tissue factor and C-reactive proteins, over a period of six months after the therapy. If they - and the antibodies to C pneumoniae - all go down, says Dr Gupta, the world's entire thinking on heart disease could be changed.
"At the moment we don't know whether chlamydia is an innocent bystander that for some reason homes in on abnormal coronary artery areas, or whether it is acting directly as a trigger for the process of the disease. The only way for us to find out is to eliminate the bug and see if that dampens down the immune system. If it does, one day patients who've had one heart attack could be antibiotics to prevent them having further attacks."
The thought that simple infection could be the root cause of long-term chronic disease is not new. Not long ago Australian doctor Barry Marshall revolutionised the way stomach ulcers are treated by proving that the vast majority are caused by the gut bacterium Helicobacter pylori. Everyone pooh-poohed the idea but now, after years of being condemned to an incurable condition and tedious regimes of bland foods and milky antacids, people with an ulcer can be cured completely with a week of antibiotics.
And there is other exciting data on C pneumoniae. Doctors studying patients with rheumatoid arthritis unexpectedly found the pathogen in the inflamed joints, but also discovered that 48 weeks of antibiotics dramatically improved the patient's pain and mobility.
Until recently, some doctors thought H pylori might be the key culprit in heart disease because research showed people with clogged arteries are more likely to be infected than healthy people. But this theory has been dashed by findings from a large project in Glasgow - "heart-disease capital of Europe" - which revealed that although more people with atherosclerosis had H pylori, they were also more likely to be older and from a lower socio-economic class which are two of the key predictors for heart disease. The strength of these two risk factors completely negated any association between H pylori and heart disease.
No such confounding factors appear to mar the suspected link with C pneumoniae. In fact, population studies have shown the bug works independently of the key traditional risk factors of age, social class, diet and smoking.
However, even if St George's experiment with eradicating C pneumoniae proves positive, there will still be lots of questions to answer says Dr Gupta. Like should antibiotics be given - just as aspirin now is - after a first heart attack to prevent a second or third? Or should they be given when other risk factors - like high cholesterol or blood pressure - signal the danger of a possible heart attack. Might susceptible people have to be on antibiotics all their lives - or could there be a vaccine against the bug which would prevent the immune system responding to C pneumoniae completely?
Given the number of premature cardiac deaths, the discovery that even a small percentage of heart disease is caused by bacteria - and is easily preventable with antibiotics - would be a major breakthrough.
And before you go abandoning those high-fat, low-fibre diets, throwing away your gym card and heading for the nearest patisserie, remember the other players of this Cluedo game of hearts are still in the room - and all have proven involvement, even if it turns out to be the bug that dun it in the end. !
ATTACK PLANS REVEALED
Infection is just one of an incredibly complex tangle of interwoven theories and research stories about the origin of heart disease. It is a field of investigation that is bewilderingly broad.
For thousands of researchers worldwide (last month's European Society of Cardiologists Congress in Birmingham was offered 7,000 reports and accepted 2,000) the key focus is biochemical and the search sites the intricate mechanisms that produce silted up arteries, faulty blood clotting, weakened heart muscles and high blood pressure.
As for so many other diseases, genetic theories also abound, though no one gene has been implicated. Some people, for example, carry abnormalities in the gene that controls the processing of fats such as cholesterol while others, new research presented by French researchers at the Congress suggests, have a quirk in the gene that governs the angiotensin-converting enzyme which regulates blood pressure.
Other investigators are pursuing the theory that it is nutrition in early life that plays the determining role in future heart disease. Population studies carried out by the University of Southampton, for example, show low birth weight babies often have abnormal heart structures, are more likely to grow up to have high blood pressure, high cholesterol levels and diabetes - three key factors that raise the risk of coronary heart disease.
But causation is by no means the only question firing up heart doctors. With more than half the 300,000 people who have a heart attack annually in Britain dying within 28 days, much work is being dedicated to finding the best way to prevent further attacks and improve the chance of survival. Here drugs which stop clotting or temper the workload of the heart are being pitted against emergency micro-surgery which not only removes the build-up of plaque within the blood vessel but uses tiny plastic tubes known as stents to keep the artery open and maintain vital blood flow.
Last but not least, there is prevention and the research findings that hit closest to home - the continued search into lifestyle factors such as smoking, diet, exercise, the menopause, and that perplexing question of whether to drink one or two glasses of red wine a day for a healthy heart.Reuse content