Primary Care Pharmacy June 2000 Vol 1 No 3 p80-83

Cardiac disease prevention

By Dougie McPhail, MSc, MRPharmS

The conference centre, Kensington town hall, London, was the venue for the 5th Cardiac Disease Prevention conference from April, 4-7. The main themes were preventable risk factors and the importance of coordinated, appropriate interventions

I am currently involved with our local health care co-operative (the Scottish equivalent of a primary care group) in assessing how to implement guidelines for the primary and secondary prevention of coronary heart disease (CHD). Attending this meeting was timely, therefore, given the calibre of the speakers, who were national and international opinion leaders in their own specialist areas of cardiovascular medicine. It was reassuring to find that the majority of presentations were familiar territory to most primary care pharmacists, with topics such as the impact of smoking and nutrition, cardiovascular aspects of diabetes and implementing guidelines and messages.
The main theme of the conference, was the overwhelming body of evidence supporting the contribution of preventable risk factors to cardiovascular disease and the effectiveness of appropriate interventions when instituted in a co-ordinated fashion. I have, therefore, selected a number of presentations that highlight this theme.

International perspectives

During the first session, Dr SRINATH REDDY from the All India Institute of Medical Sciences, New Delhi, put cardiovascular disease (CVD) into context from an international perspective.
According to the "World Health report, 1999", 30.9 per cent of all deaths in 1998, and 10.3 per cent of the total disease-related burden, in terms of disability adjusted life year lost (DALY), were attributable to CHD. In terms of ranking by country, the worst rates of CVD were in Czechoslovakia, Hungary and Scotland.
Dr Reddy indicated that the CVD "epidemic" was accelerating globally and was advancing across regions and social classes. Over the next two decades, it was estimated that the majority of this burden would be attributable to increasing incidence and the relatively young age of onset of the disease in developing countries. For example, 47 per cent of CVD deaths in developing countries in 1990 occurred in people below the age of 70. The equivalent figure for people in the high income, industrialised nations was, in contrast, 23 per cent. The impact of such premature mortality in mid-life had been quantified and it was projected that, in 2020, an estimated 6.4 million deaths would arise from CVD in the 30 to 69 year age group in developing countries.
While the dynamics of CVD in developing countries differed from those in the developed countries, the lessons learned from global experience should be utilised to avert much of the mid-life burden imposed by CVD, Dr Reddy concluded.

The global implications of smoking

Dr Reddy went on to highlight the association between passive and active smoking and the increased risk of cardiovascular events as well as acceleration of atherosclerotic vascular disease.
The exposure of the population below 35 years of age to the effects of smoking would lead to a high burden of cardiovascular disease in mid-life. The death toll arising from the effects of smoking was currently three million lives lost annually and would rise to an estimated 10 million per annum by 2030, with the developing countries accounting for some seven million of this total. If such trends continued, about one-third of the 300 million Chinese males aged under 29 would eventually be killed by the effects of tobacco consumption.
While there was overwhelming clinical evidence showing the adverse effects of smoking, an analysis by the World Bank had shown that the economic burden associated with smoking exceeded any financial benefits from the tobacco trade. The World Health Organisation was in the process of adopting an International Framework Convention on Tobacco Control to assist countries, especially developing ones, to establish effective policies for tobacco control.

Homocysteine reduction

Dr John SCOTT from the department of biochemistry, Trinity College, Dublin, gave a talk on the role of homocysteine, outlining its role as an independent risk factor for coronary heart disease.
He explained that the amino acid methionine was found to excess in the normal diet and was catabolised to the intermediate homocysteine, which had an exposed thiol group. Such groups were highly reactive and formed complexes with proteins and cell membranes if allowed to accumulate. Once formed, homocysteine was catalysed to form pyruvate, which was used for energy or remethylated back to methionine.
The status of the three enzymes responsible for this activity in turn relied on the adequacy of nutrient intake:

• Vitamin B6 for crystathionine beta synthase (catabolic reaction)
• Vitamin B12 and folate for methionine synthase (remethylation)
• Folate for 5-10 methylenetetrahydrofolate reductase (methyl groups)

Interest in homocysteine grew in the 1960s when it was discovered that children who were deficient in these enzymes because they had a rare genetic defect had high levels of homocysteine and died prematurely from cardiovascular disease. In addition, a number of retrospective studies had shown consistently that high homocysteine levels were an independent risk factor for CHD. However, a number of prospective studies had shown negative as well as positive correlation between homocysteine and CHD.
Further support for the role of homocysteine arose from a correlation shown between plasma homocysteine and carotid artery stenosis. Dr Scott suggested that an interventional trial would settle the debate on whether high homocysteine levels should be treated.
Some countries, including the US, enriched their flour with folic acid as part of a national policy and did not see the high levels of homocysteine associated with the UK. Should the UK have a similar policy and, in the meantime, did we treat patients with high homocysteine levels with folic acid 400µg daily?

Exercise

Dr Simon THOM from the Peart-Rose clinic, St Mary's hospital, London, spoke about a number of observational studies, which described the protective effects of exercise against both CHD and stroke. Taking regular exercise was associated with other positive lifestyle habits, which might confound the association of exercise with reduced CHD events. However, the protection conferred by exercise appeared to be independent of changes to other risk factors. The postulated mechanism for such action might relate to changes in skeletal muscle physiology and vascular density, sympathetic control of blood flow and adrenoceptor regulation of metabolism. Modification of thrombosis was also implicated.
Exercise was associated with a modest increase in sudden death while undertaking activity but, overall, regular participants carried a considerably reduced risk. Aerobic, dynamic exercise should be encouraged rather than isometric exercises, such as weightlifting, which caused extreme rises in blood pressure. More that 50 per cent of the UK population were at increased risk of CVD because of physical inactivity. These risk factors began in childhood and it was important to increase physical activity as part of the school curriculum.

Cholesterol reduction

Professor M LAW from St Bartholomew's hospital, indicated that the relationship between elevated cholesterol levels and CHD, and the benefits of cholesterol reduction were now well established. However, there was still debate as to the appropriateness of the level of cholesterol reduction. Should clinicians aim for a predetermined cholesterol level or undertake to lower cholesterol levels by a particular percentage from baseline?
Professor Law highlighted epidemiological evidence by country, showing a continuous log relationship between ischaemic heart disease mortality and serum cholesterol levels. This indicated that a given change in serum cholesterol levels at any point on this distribution would result in a constant, proportionate change in mortality from ischaemic heart disease. Data from China indicated that this relationship was observed down to cholesterol levels below 4mmol/L.
Cohort studies indicated that, at age 60, mortality from ischaemic heart disease declined by an estimated 27 per cent for every 10 per cent decrease in cholesterol. While subjects in some trials had relatively high baseline serum cholesterol levels, given the linear relationship between mortality from ischaemic heart disease and cholesterol levels, such decreases in mortality should also apply to patients with the lower range of cholesterol values.
Such evidence suggested that, while levels of cholesterol reduction as promoted in the British hyperlipidaemia guidelines were economically achievable, there were continued clinical benefits of achieving further levels of cholesterol reduction. If such an aim was to be achieved, its success would be determined by the efficacy and cost-effectiveness of available cholesterol lowering therapy.

Obesity

Although obesity had formerly been considered to be a problem that was generally confined to developed nations, worldwide data indicated that an increasing proportion of the population of developing countries was also affected, said professor Anthony Winder, Royal Free and University College medical school, London.
Current estimates indicated that up to one-sixth of populations of some developing countries were affected, with all the associated health problems. All available data indicated that a general, marginal shift in the balance of activity versus food intake over time was responsible for the development of weight increase. While advances in the understanding of the mechanisms of appetite and satiety were progressing apace, they would make little contribution to resolving such problems in the short term.
Current management of obese patients encouraged lifestyle changes, such as increasing activity and being more aware of food intake, choices and eating patterns. Short-term use of medication could play an important role in improving the patient's morale short-term but, in the long-term, regular behavioural support had the best track record of success in these patients.

Hypertension and treatment shortfall

Professor David BEEVERS, University department of medicine, City hospital, Birmingham, described how hypertension had been known for many years as being a major risk factor for both heart attack and stroke. The majority of long-term vascular complications associated with hypertension could be prevented if blood pressure was controlled. However, population surveys had shown that hypertension was often underdiagnosed, untreated and undertreated.
Professor Beevers indicated that a 1996 observational study of several thousand hypertensive patients in the UK showed that only 30 per cent achieved a target blood pressure of less than 160/90mmHg. Such a situation was more worrying given the results of the HOT (Hypertension Optimal treatment)¹ study, which used a target measure of 140/80mmHg. In this case, only 6 per cent of the 1996 study group would have achieved this target blood pressure.
Professor Beevers suggested the following reasons for such poor blood pressure control in the general population.

• Failure of general practitioners to diagnose hypertension
• Lack of awareness on the part of both physicians and patients of the importance of controlling blood pressure
• Poor compliance with antihypertensive regimes
• Uncontrolled blood pressure despite adequate drug therapy
• Undiagnosed underlying causes of high blood pressure
• Failure to employ non-pharmacological blood pressure lowering manoeuvres
• Inappropriate use of antihypertensive drugs

He concluded by saying that there was evidence from randomised clinical trials to show that well trained hypertension nurse specialists could achieve better results than physicians when treating hypertension. The establishment of well organised, on-going, national training programmes for nurse education in the management of hypertension and other chronic cardiovascular risk factors would appear to be a sensible strategy to improve the clinical outcomes of these patients.

Salt reduction

Professor Graham MACGREGOR from the blood pressure unit, St George's hospital medical school, London, outlined the established relationship between high salt intake and increases in blood pressure, together with the associated increases in morbidity and mortality. Carefully controlled studies of modest salt restriction showed major falls in blood pressure, whether or not the subjects were taking antihypertensive therapy. Greater reductions were observed in the elderly compared to younger patients.
Given the above evidence, Professor MacGregor recommended that the average daily intake of salt should be reduced from 10g to 5g. The salt intake of the population was increasing primarily because of greater consumption of salt-rich processed and convenience foods. These accounted for approximately 75 per cent of daily salt intake.
It had been shown that salt concentration in foods could be reduced by 10 per cent without loss of taste perception and a number of food manufacturers were beginning to do this.
"If all food manufacturers undertook an exercise of steadily reducing the salt content of processed foods over a number of years, reductions achieved would be significant enough to have a major impact on reducing strokes and coronary heart disease," said Professor MacGregor. However, salt, soft drink and some food manufacturers were opposed to such a move for commercial reasons because salt in crisps made people thirsty and encouraged the consumption of soft drinks. The estimated value of both markets was in the region of £3 billion.

The Finnish experience

Professor PEKKA PUSKA from the division of health and chronic diseases, National Public Health Institute (KTL), Helsinki, Finland, gave an overview of his experiences of the North Karelia initiative; the first successful cardiovascular disease prevention programme.
Finland in the 1960s was well known as having one of the highest rates of cardiovascular disease (CVD) and premature mortality in the world, he said. Since 1977, an active community CVD prevention programme had been carried out nationwide, taking advantage of the experience of pilot studies in the province of North Karelia. This province continued as a demonstration site for the integrated prevention of noncommunicable diseases. Such comprehensive, community-based interventions were aimed at changing the target risk factors and health behaviours (serum cholesterol, blood pressure, smoking and diet) at population level.
Age-adjusted mortality rates for CVD, CHD, all cancers, accidents and violence, and all causes in the population aged 35-64 years from the pre-programme period (1969-71) to 1995 had been assessed. During this period, age adjusted CHD mortality per 100,000 decreased in North Karelia by 73 per cent and nationwide by 65 per cent. Among men, CHD mortality continued to decrease in the 1970s, along with lung cancer mortality in the 1980s and '90s. These decreases were significantly greater in North Karelia than in all of Finland. In women, there was a great reduction in CVD mortality and all-cause mortality, but only a small reduction in cancer mortality.
The above results showed that a major reduction in CVD mortality among the working-age population could take place with active reduction of major risk factors. In addition, they produced a favourable impact on cancer and all-cause mortality. Further analysis suggested that observed changes in population cholesterol levels explained about half of the observed decline in CHD mortality. This supported the general hypothesis that changes in dietary habits, especially related to fats, was vital for the prevention of CHD in the population.

Conclusion

Overall, the conference presentations reinforced the view that cardiovascular disease was mainly a preventable condition, provided that associated risk factors were controlled in an appropriate and timely fashion. While there was an effective armamentarium of medicines, ranging from ACE inhibitors and diuretics to statins, it was disappointing to see how few people complied in taking their medicine on a regular basis and how few targets, such as blood pressure reduction, were reached, even when compliance problems had been discounted.
The UK Government, through the national service framework, is addressing coronary heart disease in England, (SIGN guidelines in Scotland), but perhaps the key to future success has been found in Finland, where cardiovascular disease is seen as a social as well as a medical problem. The success of the Finnish intervention has been as a result of numerous agencies working in a co-ordinated manner, at a local level, through local voluntary bodies, government agencies and industry. It has been driven by local communities who were concerned about the premature deaths of their men folk.
Issues, such as reducing salt and saturated fats in processed foods, the possibility of adding folic acid to flour and the banning of tobacco, require government intervention with the food and tobacco industry. Such goals must be delivered in a co-ordinated manner in order to maximise the efforts of health care professionals.
If cardiovascular disease is seen from a societal rather than a medical perspective, then perhaps we will be able to make greater reductions in the numbers of people who die prematurely in this country. Pharmacists can make a contribution to this goal by encouraging compliance/concordance in patient therapy, as well as by promoting the longer-term benefits of sensible lifestyle changes.

Mr McPhail is a primary care development pharmacist from Glenrothes, Fife

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