Gunnar Kaati

All-cause mortality of patients with dyslipidemia up to 19 years after a multidisciplinary lifestyle modification programme: a randomized trial

Background: Many studies have shown that individual lifestyle factors are associated with cardiovascular mortality and all-cause mortality. Observational studies of comprehensive programmes have reported risk reductions. The objectives were to assess the long-term all-cause mortality by diagnosis in patients referred to a lifestyle modification programme, aimed at combating coronary heart disease and stroke. Methods: A randomized trial with 325 patients referred to the centre between 1988 and 1989 for dyslipidemia, hypertension, type 2 diabetes and coronary heart disease; 239 patients were randomized to the programme, 86 randomized to usual care. Cases were admitted to the centre in groups of 30 for a 4-week residential comprehensive activity, in total 114 full-time hours, focusing on food preferences and selections, and physical exercise. The activities were repeated during a 4-day revisit to the centre 1 year and 5 years after the 4-week intervention. Controls were referred back to their doctors, mainly in primary care, for usual care. Main outcome measure was all-cause mortality during 11–12 and 18–19 years after intervention. Results: At follow-up 11–12 years after referral, the relative risk reduction (RRR) was 76% with the intention-to-treat analysis among cases admitted for dyslipidemia (hazards ratio 0.24, confidence interval 0.06–0.89, P = 0.033). After 18–19 years, the RRR was 66% (hazards ratio 0.34, confidence interval 0.13–0.88, P = 0.026). No RRR was found for the other three diagnoses. Conclusion: Patients admitted for dyslipidemia reached a real long-term RRR of all-cause mortality. They had by definition a need for this programme.

The quality and use of knowledge in health policy-making: a case study

A decision-making process about a healthcare programme is examined. The main objective of the programme was to reduce the high levels of risk factors for diseases such as coronary heart disease in individuals that conventional medical care could not handle well. The programme was ended after 10 years of operation. Why was this programme stopped and not another? Was the decision to end based on unsatisfactory performance of the programme and/or that there were better alternative uses of the resources? To answer the questions three models of decision-making will be applied to the process; special attention will be paid to the nature of knowledge on which the decision was based as well as to the logic of the process itself. The knowledge component of the process was deficient in a number of ways; nevertheless no other information was asked for by the participants. The role of the main body of the politicians in the decision-making process was extremely small. There were no traces of political ideology or a rational policy-making framework informing the decision; in fact the process was governed more by the enigmatic views of the political leadership and/or of the administrative leadership. To conclude, there is discussion of the implications of the results, especially whether the standard of knowledge, as well as the want of a systemic approach to health policy, was an aberration or reflected more common decision-making practices.

Paternal grandparental exposure to crop failure or surfeit during a childhood slow growth period and epigenetic marks on third generational growth-, glucoregulatory and stress genes

This latest in our series of papers describes transgenerational methylation related to mid-childhood food availability in 19th century Överkalix, Sweden. Failed vs. bountiful crops differentially influenced methylation in grandchildren of paternal grandparents exposed to feast or famine during their Slow Growth Period (SGP), a sensitive period preceding the pre-pubertal growth spurt. In this case-study of 8 tracked 75-year old progeny with differential ancestral exposure, we found in 40 posited gene ontology pathways 39 differentially methylated CpG regions (DMRs) related to famine, excess food and food-insecurity stress, 9 of which with DMRs above 5%. Three pathways named “insulin processing”, “adipose development” and “hypothalamus development” were sentinel with DMRs >14%. This is the first demonstration of a human transgenerational inheritance of epigenetic marks following childhood exposure to variable food availability indicating early developmental origins of adult disease.