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Keywords:

  • alcohol;
  • cardiovascular;
  • evidence;
  • hypertension;
  • lipids;
  • prevention

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. MPP – study design and outcomes
  5. Prevention of CVD
  6. Prevention of type 2 diabetes
  7. General conclusions and perspectives for the future
  8. Acknowledgements
  9. References

Abstract. Nilsson P, Berglund G (University Hospital, Malmö, Sweden). Prevention of cardiovascular disease and diabetes – lessons from the Malmö Preventive Project (Review). J Intern Med 2000; 248: 455–462.

Major public health problems such as cardiovascular disease and type 2 diabetes pose a challenge to both the medical profession and the health care system of most Western countries. In spite of widespread knowledge about risk factors and pathophysiological processes, it has been difficult to find effective preventive mass strategies based on evidence from controlled clincial trials. In the Malmö Preventive Project, Sweden, 33 346 subjects were screened for risk factors between 1974 and 1992, and a quarter of them were offered preventive help for cardiovascular disease risk or alcohol abuse. The overall finding of the project was that benefits of screening and prevention on mortality risk could only be shown in certain subgroups of younger men and women, not in the total screened cohort, as compared with a nonscreened reference population. These findings therefore question the effectiveness of preventive methods and drugs used during previous decades. New preventive methods are therefore needed and should be properly evaluated to form a basis for evidence-based prevention (EBP) in cardiovascular medicine.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. MPP – study design and outcomes
  5. Prevention of CVD
  6. Prevention of type 2 diabetes
  7. General conclusions and perspectives for the future
  8. Acknowledgements
  9. References

Cardiovascular disease (CVD) and type 2 diabetes are two major causes for premature death and serious illnesses with wide public health implications [12]. The aetiology of the two diseases has been extensively studied and has been shown to involve genetic, demographic, socioeconomic, lifestyle and metabolic factors, but the relative importance of various components in the chain of events is still not fully understood. Both are chronic diseases of long duration and both involve atherosclerotic vascular disease as a common pathway to complications. Sudden cardiac death is a common first event, as also is acute cerebrovascular disease. This clinical pattern calls for prevention as a complement to care for those who have already had an event.

Prevention can be primary (i.e. to postpone the disease, event or symptom) or secondary (i.e. to prevent recurrences or progression to disease). Primary prevention can be individually orientated involving screening for risk factors and treatment of these risk factors by pharmacological or non-pharmacological means – the so-called high-risk approach. On the other hand, primary prevention can be directed towards a whole population group. Secondary prevention is always directed towards individuals. In a recent analysis of trends in CVD mortality decline and risk factor changes in the USA, it was concluded that, taken together, primary and secondary risk factor reductions explain about 50% of this decline between 1980 and 1990 [3]. More than 70% of the overall decline in mortality has occurred amongst patients with coronary heart disease [3], which underscores the importance of secondary prevention on the individual level.

An abundance of evidence has accumulated pointing to the possibility of preventing new CVD events in subjects who have already experienced an event, using specific pharmacological tools such as antihypertensive and lipid-lowering drugs [4], and/or by multifactorial prevention including such drugs and advice to stop smoking. This high-risk approach has also been shown to prevent/postpone events in subjects previously free of disease, i.e. primary prevention [5]. However, it has been much more difficult to detect a preventive effect of intervention directed towards populations [6–9]. For type 2 diabetes only a few well-designed studies [10–12] have attempted to analyse the impact of structured care on diabetic complications.

The aim of the present paper is to review the possibilities for primary and secondary prevention of CVD and type 2 diabetes from both an individual and a population perspective, and to supply a scientific basis for the design of future preventive efforts. Where appropriate, the presentation will use examples from the Malmö Preventive Project (MPP) [13–15]. Therefore, initially, a short presentation of this project is given.

MPP – study design and outcomes

  1. Top of page
  2. Abstract
  3. Introduction
  4. MPP – study design and outcomes
  5. Prevention of CVD
  6. Prevention of type 2 diabetes
  7. General conclusions and perspectives for the future
  8. Acknowledgements
  9. References

A preventive case-finding programme for cardiovascular risk factors and alcohol abuse, the Malmö Preventive Project started at the Department of Preventive Medicine, University Hospital Malmö, in 1974. The aim was to screen large strata of the adult population in order to find high-risk individuals for preventive intervention [13–15]. Subjects were invited to participate in a broad health-screening programme, including a physical examination and a panel of laboratory tests. Additionally, every participant filled in a self-administered questionnaire on medical and personal history. Between 1974 and 1992, a total of 22 444 men and 10 902 women attended the screening programme, with an overall attendance rate of 71% (range 64–78%). Men were mostly screened in the first half of the period (1974–82), and women in the latter half (1981–92), implying different follow-up time periods for men and women. Around 25% of the screened subjects underwent various interventions (lifestyle modification, drug therapy)[1315]. These interventions were organized at a number of polyclinics aiming at treatment of hypertension, hyperlipidaemia, impaired glucose tolerance, alcohol overconsumption, etc. (Fig. 1).

image

Figure 1. Schematic description of the baseline examination and intervention with percentage of participants referred to the various treatment clinics. © 1983 Preventive Medicine12: 397–402; printed with permission from Academic Press.

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Intervention programmes on risk factors

The Section of Preventive Medicine was an integrated part of the Department of Medicine, Malmö University Hospital, and occupied facilities close to the hospital for screening and for diagnosis and treatment of those subjects with diseases and/or risk factors detected at screening. The intervention programme was therefore an individually orientated, high-risk approach with resources set aside for both screening and subsequent treatment. The criteria for intervention and the numbers of subjects who underwent interventions were described in 1983 [13]. The results of intervention on the risk factors hyperlipidaemia [1617], impaired glucose tolerance [18–20] and alcohol overconsumption [2122] have been published previously.

Ascertainment of cases

All subjects who attended the baseline examination have been traced in national or local registers. Additionally, we used local population censuses to identify non-attenders. These were defined as: (i) subjects born in the same year as the attendees; and (ii) living in Malmö in the year when written invitations to screening were sent out. All available subjects were followed for a mean of 17 years in national registers for total and cause-specific mortality: ischaemic heart disease. The cause of death was based on autopsy in 44% of the cases, which implies that overall the diagnoses on death certificates should be reasonably trustworthy. For the long-term outcome analysis, a control group of non-invited birth cohorts was constructed [15].

Effects on mortality and interpretation of results

Twenty-five years after the start of the project, the MPP recently analysed the intervention effects of this comprehensive, multifactorial screening and intervention programme against CVD, breast cancer and high alcohol consumption [15]. The findings of the MPP are very much in line with other reports on community interventions [6–9], but are also, in certain respects, somewhat more hopeful.

No effect of intervention was shown on mortality and cardiovascular morbidity in the intervention group as a whole.

There was also a lower total mortality in men under the age of 40 at entry, probably due to a lower mortality from alcohol-related diseases.

There was also a lower total mortality in women under the age of 40 at entry due to lower mortality from cancer.

The interpretation of these findings is that risk factor screening and intervention in an urban setting such as the one in Malmö, and the use of the contemporary methods of the MPP, are not enough to reduce all-cause mortality more than implied by population time trends. On the other hand, this kind of project may show advantages for certain subgroups of subjects according to age and gender. This is important in view of the heterogeneity in the distribution and determinants of ischaemic heart disease (IHD) that has been reported when comparing different geographical areas of Malmö[2324]. People living in more socially deprived areas of Malmö have more cardiovascular risk factors and a higher incidence of IHD than found in less deprived areas [24]. The non-attenders (25–30%) in the MPP seemed to belong to these less privileged groups [15], a matter of great concern for the extrapolation of results to whole populations.

Prevention of CVD

  1. Top of page
  2. Abstract
  3. Introduction
  4. MPP – study design and outcomes
  5. Prevention of CVD
  6. Prevention of type 2 diabetes
  7. General conclusions and perspectives for the future
  8. Acknowledgements
  9. References

Population approaches

Studies on the prevention of a cardiovascular disease in a population carry specific scientific problems, as recently summarized by Thelle [25]. In individuals (high-risk approach) risk factors can be identified and intervened upon by non-pharmacological and/or pharmacological tools. The changes in risk factor levels can easily be monitored. It becomes much more complex to determine attitudes, behaviours, lifestyle changes, the risk factor burden and outcome measures such as mortality and morbidity in the whole population. The cause/effect relationship is thus harder to identify. Furthermore, the risk in healthy ‘normal’ individuals is much lower than in high-risk individuals. Clinical events will thus occur much more infrequently in such normal populations than in high-risk groups, necessitating much larger study groups to achieve sufficient statistical power. It is therefore not astonishing that the population-based intervention programmes have had problems in showing positive results [6–9]. The only other Swedish project that is comparable to the MPP is the Gothenburg Primary Preventive Trial (GPPT) [9]. In this study, middle-aged men were screened and treated for cardiovascular risk factors, but no overall beneficial effect could be detected in total or CVD mortality in comparison with a predetermined control group [9]. Dietary advice, smoking cessation and drug treatment, if necessary, for hypertension and hyperlipidaemia were all integrated parts of this programme, but there were no activities focusing on alcohol overconsumption or health problems of women such as those in the MPP. The similarities between the two studies are obvious and neither of them could show a preventive effect on cardiovascular outcomes over and above that seen in the general background population of the two cities.

Surprisingly, the WHO, the National Institute for Heart, Lung and Blood Disease (NHBLI), as well as other organizations have all recommended radical changes in lifestyle in spite of the lack of scientific evidence for a preventive effect of large-scale community studies. Included in the lifestyle advice are measures such as smoking cessation, improved diet, decreased alcohol consumption and enhanced physical activity for whole populations. Other lines of argument must have been used when these political health goals were set. Apart from cessation of smoking, the suggested lifestyle changes have a relatively weak scientific basis for effectiveness on the population level. The Swedish Council of Technology Assessment in Health Care has recently published an extensive review of population-based preventive efforts in defined communities [26]. This review identified eight large preventive projects in Europe and the USA with the whole population as target group. For inclusion, these projects should:

  • • 
    be directed towards more than one risk factor;
  • • 
    follow the changes in risk factors, morbidity and mortality in a comparable control population as well;
  • • 
    have published the results in scientific journals.

In summary, these large community projects showed no or insignificant beneficial effects in the intervention communities as compared with the control areas [26], and the review presented the following conclusions and recommendations.

Smoking, high blood pressure, unhealthy dietary habits, low physical activity and social factors seem to play a role in the development of CVD. However, the review gave no scientific basis for starting new, large population-based intervention projects with the tools that were used in the scrutinized projects.

Several attempts to prevent CVD are in progress in Sweden and elsewhere. They are seldom designed in a way that makes proper evaluation of the effects possible. The scientific competence in these projects should therefore be strengthened.

The evaluation of the intervention effects in population-based projects needs development of new methodology, not least within the social and behavioural processes involved in preventive efforts in the population.

The review deals with preventive projects with design and methods of the 1970s and 1980s, with the inherent problem of generalizing the findings to the present situation. The important task of preventing disease should be based on scientifically proven facts. The knowledge gained from these large population-based preventive projects should be looked upon as a basis for more focused studies on how CVD can and should ideally be prevented in the future.

Why did the large projects fail to show expected results? There are several explanations. The similar risk factor decrease in both intervention and control areas in most studies, which might imply seeding of information from the project area to the control area, is one major possibility. Another possibility is use of ineffective methods for diagnosis, treatment and follow-up with regard to both lifestyle and pharmacological interventions. A third is lack of knowledge of the psychological and social mechanisms involved in changing attitudes and behaviours, not only of individuals but of whole populations. In future preventive programmes, social scientists should therefore ideally be involved in both design and implementation at an early stage. Whatever the reason(s), the findings of the large population-based project call for future research with more stringent design and more effective interventions [20].

High-risk individual approach

The three well-known major risk factors for CVD – hypertension, hyperlipidaemia and smoking – have all been addressed in randomized controlled trials (RCTs). Different populations and treatment strategies have been involved, but mostly with a selection bias towards middle-aged Caucasian men and drug treatment. The overall conclusion to be drawn from a meta-analysis of antihypertensive RCTs is that a mean net diastolic blood pressure reduction of about 5 mmHg has been associated with a 40% relative reduction of stroke and a 14–18% relative reduction in the incidence of myocardial infarction [27], having the largest benefits in elderly hypertensives. Older antihypertensive drugs are equally as effective as more modern ones in elderly hypertensives [28]. The angiotensin-converting enzyme (ACE) inhibitors have additional protective properties independent of the blood pressure effect, as recently shown with ramipril in the HOPE study [29]. It should, however, be pointed out that in these cited studies, the absolute risk reduction has been rather modest, being less than 10% over a 3–5-year time period. The absolute risk is the only risk of personal importance to the patient.

Treatment of hyperlipidaemia has been well documented in the 1990s for both primary prevention [3031] and secondary prevention [32–34], and seems cost-effective in specific subgroups of patients, e.g. in type 2 diabetes in a secondary preventive trial [35]. Statins have mostly been used in recent RCTs and are proven to be safe and effective [30–34]. However, the absolute risk reduction in these studies has been modest. In Malmö, the treatment of hyperlipidaemia was an integral part of the intervention programme of MPP, focusing on the special risk category of combined hypercholesterolaemia and hypertriglyceridaemia, with good results on risk factor levels [1617].

Smoking is perhaps the risk factor for CVD which theoretically should be the most cost-effective to treat, and is a very well proven risk factor for many disorders in long-term observational studies. Advice for smoking cessation has been incorporated more or less successfully in the majority of RCTs for prevention of CVD, but it should be pointed out that well-designed intervention studies on smoking cessation are few. One of the most convincing studies so far to prove the benefits of smoking cessation is the Oslo Diet and Anti-smoking Study with very favourable long-term results [36]. A more healthy diet in combination with smoking cessation was shown to decrease CVD mortality drastically. In the MPP, smoking cessation was recommended to many patients at risk, but evaluation of separate effects of quitting smoking has not been possible due to insufficient follow-up data on smoking habits.

Prevention of type 2 diabetes

  1. Top of page
  2. Abstract
  3. Introduction
  4. MPP – study design and outcomes
  5. Prevention of CVD
  6. Prevention of type 2 diabetes
  7. General conclusions and perspectives for the future
  8. Acknowledgements
  9. References

Population approach

Type 2 diabetes represents a growing public health problem in most countries, and according to new criteria published by WHO Collaboration [37] 5–10% of the adult population in Western countries would have a diagnosis of type 2 diabetes if proper screening of the entire population was implemented. Preventive efforts have been discussed for at least two decades, but so far only very few studies have tried to tackle the problem on the population level. In Stockholm, Sweden, the Diabetes Prevention Programme has been running for a few years with the aim of lowering complications in the population of intervention communities compared with that of a control area [38]. No outcome results are so far available.

High-risk and individual approaches

In the MPP an active attitude towards screening and intervention in middle-aged men with impaired glucose tolerance (IGT) has produced evidence for long-lasting beneficial effects compared with a non-randomized control group [18–20]. This has mainly been achieved by putting emphasis on promoting regular physical exercise and, to a lesser degree, dietary advice. It was shown that regular physical exercise could improve glucose metabolism and decrease morbidity and mortality, as compared with a reference group during a follow-up of 12 years. Similarly, in the USA, a screening project for IGT has developed into a RCT comparing lifestyle intervention with drug treatment (metformin) for the prevention of conversion of IGT to overt type 2 diabetes [39], but outcome results are not yet available.

In the high-risk approach for prevention of diabetes, treatment of hyperglycaemia and hypertension should also be included. This has been tried in type 2 diabetes, for hyperglycaemia in the UGDP [10] and the UKPDS [1112] studies, and for hypertensive patients in a substudy of the UKPDS [40]. The results indicate that aggressive treatment to lower hyperglycaemia and high blood pressure decreased diabetic and microvascular complications. Several other recent studies of antihypertensive treatment in the 1990s have included subanalyses of effects in type 2 diabetes patients, corroborating the UKPDS findings (e.g. data from the SHEP, HOT, CAPPP, SYST-EUR, and STOP-2 studies).

The role of prevention – need for more studies?

This review of the possibilities of preventing CVD and type 2 diabetes, with some examples chosen from the MMP, illustrates that prevention must also be evidence-based. The individually orientated approach has often used designs that allowed proper analyses of the interventional effects. With this approach, CVD can be prevented through modern effective drug treatment of high blood pressure and hyperlipidaemia and by stopping smoking. Earlier studies, using older drugs and interventions, were sometimes not successful during long-term follow-up, and at least one study showed a detrimental effect on mortality [41]. The population-based programmes of the 1970s and the 1980s have not been able to show the same effectiveness in the total population, probably due to a combination of factors. These included ineffective measures to change behaviour, too low a participation in intervention programmes, and concomitant changes in risk factor levels and CVD mortality and morbidity in the control populations. Future preventive efforts would need to develop programmes that combine the population and individual approaches, including screening for risk factors and their treatment. These programmes should preferably be evidence-based and not based only on ad hoc consensus group guidelines, which is often the case today.

There has so far been no population-based study published on primary prevention of diabetes. Such a study – although difficult to design and carry out – should have high priority. The current epidemic of obesity and lower physical activity will probably have a deleterious influence on incidence of type 2 diabetes [37]. The individually orientated studies on prevention of diabetic complications have given promising results [1112]. Better treatment of diabetes mellitus with better glycaemic control and control of blood pressure was shown to protect against macrovascular [1240] and microvascular [1140] complications. These data need to be translated into more overall effective care of the diabetic patient in primary care and in hospitals, as recently shown in the HOPE diabetes substudy [42].

Future preventive programmes, whether they are directed towards CVD or type 2 diabetes, or both, have to use behavioural sciences to a larger extent than the programmes discussed in this review. Effective measures must be developed to influence lifestyle very early, probably as early as at day-care centres and schools. Means for worksite lifestyle influences should also be implemented. Genetic markers will probably help us in directing specific preventive efforts to targeted subjects with a strong hereditary component of their disease risk, and at the same time allow us to avoid intervention where it is not deemed effective.

The new millennium might prove to be very prosperous for researchers engaged in prevention of cardiovascular diseases and diabetes mellitus. A difficult problem still unanswered is how to reach non-participants in preventive programmes. Previous studies, including the MPP, have shown that non-participants are selected towards negative health and social deprivation with an overall higher risk profile [154344]. Therefore, future prevention programmes need to incorporate new methods to reach a larger fraction of the population, especially those in socially deprived areas.

General conclusions and perspectives for the future

  1. Top of page
  2. Abstract
  3. Introduction
  4. MPP – study design and outcomes
  5. Prevention of CVD
  6. Prevention of type 2 diabetes
  7. General conclusions and perspectives for the future
  8. Acknowledgements
  9. References

In summary, prevention of CVD and type 2 diabetes still represents a great challenge with the potential to reduce a considerable proportion of the global burden of disease [12]. An individual approach has to be combined with population-based approaches, but the entire programme should be based on evidence. Eventually, it might well prove to be true that population-based approaches for a whole country turn out to be similarly or even more cost-effective than individual approaches to reduce IHD risk, e.g. by influencing lipid levels [4546]. A proper evaluation of large-scale community or national projects will, however, always be much more difficult than the corresponding evaluation of individually targeted projects. New, and hopefully more effective, intervention methods on different structural levels, from the individual to the society, will sooner or later replace old methods, and the concept of evidence-based prevention, which we advocate, will eventually be realized.

Our own experiences from the MPP [15], in addition to the experiences from the Gothenburg Primary Prevention trial [9], have led us to believe that a hospital-based prevention programme alone is not effective for primary prevention of cardiovascular disease in a local population. Individual screening efforts in the primary health care setting are also problematic for many reasons, not least because of the high numbers of at-risk individuals found [47] and the lack of long-term effects [4849]. Opportunistic individual screening of cardiovascular risk factors in patients seeking medical care for various reasons and at different health care levels might be a more realistic and cost-effective approach for the future, but this has to be proven in new end-point studies. Improved quality assurance of secondary prevention [50] and screening of members of families with a high burden of CVD [34] are other ways which seem to be potentially cost-effective, even though only minor segments of the total population are reached.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. MPP – study design and outcomes
  5. Prevention of CVD
  6. Prevention of type 2 diabetes
  7. General conclusions and perspectives for the future
  8. Acknowledgements
  9. References

This study was supported by the Swedish Medical Research Council and the Swedish Society of Medicine. Figure 1 has been reproduced by kind permission of Academic Press, © 1983 Preventive Medicine: 1983; 12: 397–402.

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  1. Top of page
  2. Abstract
  3. Introduction
  4. MPP – study design and outcomes
  5. Prevention of CVD
  6. Prevention of type 2 diabetes
  7. General conclusions and perspectives for the future
  8. Acknowledgements
  9. References
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Received 10 March 2000; revision received 26 July 2000; accepted 10 August 2000.