Change in paternal grandmothers' early food supply influenced cardiovascular mortality of the female grandchildren.

BACKGROUND: This study investigated whether large fluctuations in food availability during grandparents' early development influenced grandchildren's cardiovascular mortality. We reported earlier that changes in availability of food - from good to poor or from poor to good - during intrauterine development was followed by a double risk of sudden death as an adult, and that mortality rate can be associated with ancestors' childhood availability of food. We have now studied transgenerational responses (TGR) to sharp differences of harvest between two consecutive years' for ancestors of 317 people in Överkalix, Sweden. RESULTS: The confidence intervals were very wide but we found a striking TGR. There was no response in cardiovascular mortality in the grandchild from sharp changes of early exposure, experienced by three of the four grandparents (maternal grandparents and paternal grandfathers). If, however, the paternal grandmother up to puberty lived through a sharp change in food supply from one year to next, her sons' daughters had an excess risk for cardiovascular mortality (HR 2.69, 95% confidence interval 1.05-6.92). Selection or learning and imitation are unlikely explanations. X-linked epigenetic inheritance via spermatozoa seemed to be plausible, with the transmission, limited to being through the father, possibly explained by the sex differences in meiosis. CONCLUSION: The shock of change in food availability seems to give specific transgenerational responses.

Migration and mortality trajectories: a study of individuals born in the rural community of Överkalix, Sweden.

Migration may result in exposure to factors that are both beneficial and harmful for good health. How the act of migration is associated with mortality, or whether the socio-economic condition of migrants prior to migration influences their mortality trajectory, is not well understood. In the present study, a cohort of 413 randomly selected individuals born in the rural community of Överkalix, Sweden, between 1890 and 1935 were followed from birth to either death or old age. Around 50% of the study-population moved away from Överkalix at one time or another. To adjust for a potential bias resulting from self-selection among the migrants, the father's occupational status was used together with parents' and grandparents' longevity. Overall, migration could not be shown to predict mortality when the backgrounds of the migrants were taken into account. Nonetheless, socio-economic background conditions appeared to moderate the association, decreasing the mortality rates for migrants with relatively good pre-migratory socio-economic conditions, while increasing it for migrants with poorer pre-migratory conditions. However, further scrutiny revealed that this effect modification mainly affected the female migrants' mortality. In conclusion, the study suggests that there is no general association between migration and mortality, but that migrants with better socio-economic resources are more likely to improve their mortality trajectories than migrants with poorer resources. Better pre-migratory conditions hence appear to be important for avoiding health-adverse circumstances and gaining access to health beneficial living conditions when moving to foreign environments - especially for women.

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 11­12 and 18­19 years after intervention. RESULTS: At follow-up 11­12 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 0.06­0.89, P = 0.033). After 18­19 years, the RRR was 66% (hazards ratio 0.34, confidence interval 0.13­0.88, 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.

Transgenerational response to nutrition, early life circumstances and longevity.

Nutrition might induce, at some loci, epigenetic or other changes that could be transmitted to the next generation impacting on health. The slow growth period (SGP) before the prepubertal peak in growth velocity has emerged as a sensitive period where different food availability is followed by different transgenerational response (TGR). The aim of this study is to investigate to what extent the probands own childhood circumstances are in fact the determinants of the findings. In the analysis, data from three random samples, comprising 271 probands and their 1626 parents and grandparents, left after exclusions because of missing data, were utilized. The availability of food during any given year was classified based on regional statistics. The ancestors' SGP was set at the ages of 8-12 years and the availability of food during these years classified as good, intermediate or poor. The probands' childhood circumstances were defined by the father's ownership of land, the number of siblings and order in the sibship, the death of parents and the parents' level of literacy. An earlier finding of a sex-specific influence from the ancestors' nutrition during the SGP, going from the paternal grandmother to the female proband and from the paternal grandfather to the male proband, was confirmed. In addition, a response from father to son emerged when childhood social circumstances of the son were accounted for. Early social circumstances influenced longevity for the male proband. TGRs to ancestors' nutrition prevailed as the main influence on longevity.

Sex-specific, male-line transgenerational responses in humans.

Transgenerational effects of maternal nutrition or other environmental 'exposures' are well recognised, but the possibility of exposure in the male influencing development and health in the next generation(s) is rarely considered. However, historical associations of longevity with paternal ancestors' food supply in the slow growth period (SGP) in mid childhood have been reported. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we identified 166 fathers who reported starting smoking before age 11 years and compared the growth of their offspring with those with a later paternal onset of smoking, after correcting for confounders. We analysed food supply effects on offspring and grandchild mortality risk ratios (RR) using 303 probands and their 1818 parents and grandparents from the 1890, 1905 and 1920 Overkalix cohorts, northern Sweden. After appropriate adjustment, early paternal smoking is associated with greater body mass index (BMI) at 9 years in sons, but not daughters. Sex-specific effects were also shown in the Overkalix data; paternal grandfather's food supply was only linked to the mortality RR of grandsons, while paternal grandmother's food supply was only associated with the granddaughters' mortality RR. These transgenerational effects were observed with exposure during the SGP (both grandparents) or fetal/infant life (grandmothers) but not during either grandparent's puberty. We conclude that sex-specific, male-line transgenerational responses exist in humans and hypothesise that these transmissions are mediated by the sex chromosomes, X and Y. Such responses add an entirely new dimension to the study of gene-environment interactions in development and health.

Outcomes of comprehensive lifestyle modification in inpatient setting.

OBJECTIVE: To examine the effectiveness of a 4-week inpatient non-pharmacological risk factor modification programme for individuals with the metabolic syndrome. The aim of the program was to reduce patients' over risks for stroke and myocardial infarction. METHODS: A prospective clinical study including 2468 patients--1096 men and 1372 women--with and average age of 50 +/- 10 years. The patients were referred to the programme from primary care units and hospitals where treatment options were exhausted. RESULTS: All risk factor levels for stroke and myocardial infarction decreased. The reduction of weight among men was 4.7 +/- 2.6 kg and 3.8 +/- 1.8 kg among women from an initial weight of 96 +/- 17 kg and 85 +/- 16 kg, respectively. The patients systolic and diastolic blood pressure decreased by 15/10 mmHg for men and 14/9 mmHg among women from initial average for the whole population of 148/90 +/- 19/11 mmHg and 146/87 +/- 19/12 mmHg, respectively. The greatest decrease in weight and blood pressure occurred in men and women with an initial body mass index of > or = 30 and with a diastolic blood pressure of > or = 90; in this group, the average reductions in weight were 5.8 +/- 2.4 kg for men and 4.4 +/- 1.7 kg for women; the reductions in systolisk/diastolisk blood pressure were 22/15 +/- 16/9 mmHg (p < 0.001) for both men and women. A reduction of medication (DDD) although not a goal was also achieved. CONCLUSION: The results prove the value of a comprehensive and highly structured inpatient approach to lifestyle modification. PRACTICE IMPLICATIONS: The results should give cause to trials with half-way strategies integrating features from the inpatient programme into the design of risk factor interventions.