Age may not be the unmodifiable risk factor for cardiovascular disease that it is currently believed to be. It can broken down into factors which are, as thought, “unstoppable”, and others which can be modified, particularly if tackled early enough. These are the conclusions of authors of a Viewpoint published early Online and in an upcoming edition of the Lancet.
Dr Allan Sniderman, Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University, Montreal, Quebec, Canada, and Dr Curt Furberg, Wake Forest University School of Medicine, North Carolina, USA, say: “Age is not considered to be a modifiable risk factor but unfortunately it outranks all those that are – eg, lipids, blood pressure and smoking – as a predictor of clinical events. If so, a tight limit exists on how much prevention can be achieved. But is conventional wisdom correct" Are all the effects of age immutable"”
Atherosclerosis – building up of plaques in the arteries – can eventually by fatal, by causing a blockage (thrombus) that can rapidly slow or stop blood flow, leading to death of the tissue fed by the artery (infarction). A heart attack due to a coronary artery plaque build up is an example of this. The authors ask: “How do we deal with the dilemma that atherosclerosis is often well underway before middle age whereas clinical complications are common only after middle age"”
Results of epidemiological studies are contradictory. Some analyses have shown that the classic modifiable risk factors for cardiovascular disease such as abnormal levels of circulating fats, smoking, and high blood pressure are major determinants of risk. Others have demonstrated just as clearly that age and gender are virtually all that matter. The key to effective prevention is to resolve this paradox and that is the aim of this Viewpoint.
The effect of risk factors such as abnormal levels of circulating fats on the development of disease is related to both the magnitude of the condition and its duration. Thus, just as certain fats (high LDL) pose higher risk than others (low LDL), exposure to raised concentrations of high LDL over 30 years would be expected to cause more vascular disease than the same exposure over three years. The authors say: “This last point is key. Conventional analyses do not distinguish between the biological changes within arteries – the non-modifiable effects of disintegration of tissues over time – and those produced by exposure over time to risk factors such as atherogenic dyslipoproteinaemia.”*
The authors refer to a number of studies (INTERHEART, AMORIS) that show that abnormal levels of circulating fats which lead to artherosclerosis are not merely risk factors for vascular disease - they cause it - as do high blood pressure and smoking. They underline that because of this, when present and pronounced, these factors should be taken seriously without losing significance in the complicated statistical calculations of risk, which can mask their true effect. They also draw attention to the problems of epidemiological studies focussing on middle-aged populations for only short periods – obscuring the appreciation of the true importance of the modifiable factors that cause vascular disease.
Coronary disease can be substantial even in a person’s 20s, and thus early intervention will produce early benefits. The authors say: “Success is more probable if we prevent atherosclerosis from diffusely invading and completely distorting the arterial tree than if we attempt to intervene in only the final stages.” While lifestyle changes are important to advocate, they are unlikely to be adequate, especially for those with pronounced abnormal blood pressure or abnormal blood fats. The authors focus on drug treatment, its costs and side effects, and when it is most appropriate to begin it or delay it to. For example statins, which have few side effects and many of which are at or beyond the end of their patents, bringing costs down. Identification of key risk groups – eg, those with abnormal LDL values, would have the most to gain though early drug treatment. Those with less pronounced abnormalities could start treatment later.
The authors conclude: “Age can be deconstructed into time-related effects of disintegration that affect all of us versus time-related effects of exposure to the modifiable causal factors that affect some of us more than others. This crucial distinction is not taken into account by the methods we use to predict risk.
“The natural history of coronary disease can be likened to a three-act tragedy. The first act introduces and develops the main characters – namely, atherogenic dyslipoproteinaemia, high blood pressure, and smoking – that appear as we mature and unless something is done, persist during our lifetime. During the second act, which also takes place over decades, these villains incessantly attack and progressively deform the innocent arterial wall. Finally, the third act, which can be tragically brief: in an instant, the plaque ruptures, the artery thromboses, and the hero or heroine dies, all too frequently unaware of the drama that was enacted within their arteries. What is the difference, you ask" In the drama of coronary disease, the ending is not fixed; if some of the characters are edited out of the play as soon as they appear, the third act need never take place.”
Notes to editors: *atherogenic dyslipoproteinaemia is abnormal levels of circulating fats which leads to atherosclerosis.
Dr Allan Sniderman, Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University, Montreal, Quebec, Canada T) +1 514-909-4919 E) allansniderman@hotmail.com
Dr Curt Furberg, Wake Forest University School of Medicine, North Carolina, USA T) +1 336-716-3730 but best contact via e-mail: E) cfurberg@wfubmc.edu
Journal
The Lancet