Peeters, A.

Genetic variants of FOXP3 influence graft survival in kidney transplant patients (Article)

2013-03-25T00:00:00Z

FOXP3+regulatory T cells (Treg) play a role in controlling alloreactivity. It has been shown that short (GT)ndinucleotide repeats (≤(GT)15; S) in the promoter region of the FOXP3 gene enhance the promoter activity when compared to long (GT)nrepeats (≥(GT)16; L). The present study retrospectively investigated the influence of this (GT)nFOXP3 gene polymorphism on renal allograft survival. A total of 599 consecutive first-time kidney transplant patients (median follow-up time 7.7 years) were subdivided according to their FOXP3 genotype into the S-genotype group (SG) and the L-genotype group (LG). The SG was superior to the LG in both general graft survival censored for death (logrank test, p = 0.013) and graft survival following acute rejection (p = 0.021). Multivariate analysis defined the (GT)nFOXP3 dinucleotide repeat polymorphism as an independent factor and confirmed an advantage for the SG in renal allograft survival (HR = 0.67, 95% CI 0.48-0.94, p = 0.02). This gene association study identified a beneficial effect of FOXP3 genetic variants on graft survival in kidney transplant patients.

The functional polymorphism Ala258Ser in the innate receptor gene ficolin-2 in the donor predicts improved renal transplant outcome (Article)

2012-09-15T00:00:00Z

BACKGROUND: Innate immunity plays a role in controlling adaptive immune responses. METHODS: We investigated the clinical relevance of single nucleotide polymorphisms in 22 genes encoding innate, secreted, and signaling pattern recognition receptors in a total of 520 donor-recipient pairs of postmortem, human leukocyte antigen-DR-compatible kidney transplantations. Associations with rejection incidence were tested in an a priori randomized training set and validation set. RESULTS: Polymorphisms in TLR-3 (rs3775296) in the recipients and in Ficolin-2 (rs7851696; Ala258Ser) and C1qR1 (rs7492) in the donors showed the strongest association with severe rejection. In multivariate analysis, presence of the Ficolin-2 Ala258Ser variant in the donor predicted lower incidence of severe rejection (odds ratio=0.3; 95% confidence interval, 0.1-0.9; P=0.024) and of graft loss (hazard ratio=0.5; 95% confidence interval, 0.2-1.0; P=0.046) independently of clinical risk factors. Ficolin-2 messenger RNA expression was detected in pretransplantation biopsies from 69 donor grafts. Serum and tissue Ficolin-2 levels were unaffected by genotype. Ficolin-2 protein, which bound to dying cells, was detected in donor kidneys in a passenger leukocyte-like pattern. Indeed, monocytes, monocyte-derived macrophages, and peripheral blood mononuclear cells expressed Ficolin-2. Donor grafts with the Ficolin-2 Ala258Ser variant contained significantly elevated expression of interleukin 6, having ascribed cytoprotective effects. It has been described that Ala258Ser leads to increased binding capacity of Ficolin-2 to N-acetylglucosamine. CONCLUSIONS: Presence of the Ficolin-2 Ala258Ser polymorphism in the donor independently predicts improved graft outcome. Based on mechanistic data, we propose that this functional polymorphism leads to more efficient handling of injured cells by phagocytozing cells, resulting in decreased intragraft exposure to danger signals and dampened alloimmune responses. Copyright

Age-specific trends in cardiovascular mortality rates in the Netherlands between 1980 and 2009 (Article)

2011-05-01T00:00:00Z

Recent analyses suggest the decline in coronary heart disease mortality rates is slowing in younger age groups in countries such as the US and the UK. This work aimed to analyse recent trends in cardiovascular mortality rates in the Netherlands. Analysis was of annual all circulatory, ischaemic heart disease (IHD), and cerebrovascular disease mortality rates between 1980 and 2009 for the Netherlands. Data were stratified by sex and 10-year age group (age 35-85+). The annual rate of change and significant changes in the trend were identified using joinpoint Poisson regression. For almost all age and sex groups examined the rate of IHD and cerebrovascular disease mortality in the Netherlands has more than halved between 1980 and 2009. The decline in mortality from both IHD and cerebrovascular disease is continuing for all ages and sex groups, with anacceleration in the decline apparent from the late 1990s/early 2000s. The decline in age-specific all circulatory, coronary heart disease and cerebrovascular disease mortality rates continues for all age and sex groups in the Netherlands.

Discontinuation of calcineurin inhibitors treatment allows the development of FOXP3+ regulatory T-cells in patients after kidney transplantation (Article)

2011-01-01T00:00:00Z

This study investigated specific gene expression profiles in patients with donor-specific cytotoxic-hyporesponsiveness, reflected by cytotoxic T-lymphocyte precursor frequency (CTLpf). The effect of calcineurin inhibitor (CNI) withdrawal was studied on markers for cytotoxicity (perforin, granzyme B), apoptosis (Fas,FasL), Th1 and Th2 cytokines (IL-2, IL-10), Th1 and Th2 transcription factors (T-bet, GATA 3), Th17 transcription factor and cytokine (RORγt, IL-17), and for immune regulation/activation (CD25, FOXP3). Peripheral blood samples from renal allograft recipients (n=18) more than twoyr after transplantation with stable renal function were analyzed before and fourmonths after CNI withdrawal. Additionally, systolic and diastolic blood pressure, cholesterol, serum creatinine and proteinuria were evaluated, and no significant differences were measured before and after CNI withdrawal. However, CNIs' discontinuation influenced peripheral gene expression profiles. After CNI withdrawal, the mRNA expression of Granzyme B, Perforin, Fas, FasL, T-bet, GATA3 and CD25 were significantly lower than during CNI treatment. After CNI discontinuation, donor-specific CTLpf decreased, while FOXP3 expression discriminated between detectable and non-detectable donor-specific cytolysis reactivity; FOXP3 transcript values were highest in absence of donor-specific cytotoxicity (p<0.01). Our study shows CNI withdrawal in stable kidney transplant recipients twoyr after transplantation is safe. Moreover, discontinuation of CNIs' treatment allows FOXP3+ regulatory T-cells development, resulting in a significant decrease of anti-donor immune reactivity.

Living healthier for longer: Comparative effects of three heart-healthy behaviors on life expectancy with and without cardiovascular disease (Article)

2009-12-01T00:00:00Z

Background. Non-smoking, having a normal weight and increased levels of physical activity are perhaps the three key factors for preventing cardiovascular disease (CVD). However, the relative effects of these factors on healthy longevity have not been well described. We aimed to calculate and compare the effects of non-smoking, normal weight and physical activity in middle-aged populations on life expectancy with and without cardiovascular disease. Methods. Using multi-state life tables and data from the Framingham Heart Study (n = 4634) we calculated the effects of three heart healthy behaviours among populations aged 50 years and over on life expectancy with and without cardiovascular disease. For the life table calculations, we used hazard ratios for 3 transitions (No CVD to CVD, no CVD to death, and CVD to death) by health behaviour category, and adjusted for age, sex, and potential confounders. Results. High levels of physical activity, never smoking (men), and normal weight were each associated with 20-40% lower risks of developing CVD as compared to low physical activity, current smoking and obesity, respectively. Never smoking and high levels of physical activity reduced the risks of dying in those with and without a history of CVD, but normal weight did not. Never-smoking was associated with the largest gains in total life expectancy (4.3 years, men, 4.1 years, women) and CVD-free life expectancy (3.8 and 3.4 years, respectively). High levels of physical activity and normal weight were associated with lesser gains in total life expectancy (3.5 years, men and 3.4 years, women, and 1.3 years, men and 1.0 year women, respectively), and slightly lesser gains in CVD-free life expectancy (3.0 years, men and 3.1 years, women, and 3.1 years men and 2.9 years women, respectively). Normal weight was the only behaviour associated with a reduction in the number of years lived with CVD (1.8 years, men and 1.9 years, women). Conclusions. Achieving high levels of physical activity, normal weight, and never smoking, are effective ways to prevent cardiovascular disease and to extend total life expectancy and the number of years lived free of CVD. Increasing the prevalence of normal weight could further reduce the time spent with CVD in the population.

Donor-derived mesenchymal stem cells remain present and functional in the transplanted human heart (Article)

2009-01-01T00:00:00Z

Mesenchymal stem cells (MSC) are characterized by their multilineage differentiation capacity and immunosuppressive properties. They are resident in virtually all tissues and we have recently characterized MSC from the human heart. Clinical heart transplantation offers a model to study the fate of transplanted human MSC. In this study, we isolated and expanded MSC from heart tissue taken before, and 1 week up to 6 years after heart transplantation. MSC from posttransplantation tissue were all of donor origin, demonstrating the longevity of endogenous MSC and suggesting an absence of immigration of recipient MSC into the heart. MSC isolated from transplanted tissue showed an immunophenotype that was characteristic for MSC and maintained cardiomyogenic and osteogenic differentiation capacity. They furthermore preserved their ability to inhibit the proliferative response of donor-stimulated recipient peripheral blood mononuclear cells. In conclusion, functional MSC of donor origin remain present in the heart for several years after transplantation.

Lifetime risk and projected population prevalence of diabetes (Article)

2008-12-01T00:00:00Z

Aims/hypothesis: With incidence rates for diabetes increasing rapidly worldwide, estimates of the magnitude of the impact on population health are required. We aimed to estimate the lifetime risk of diabetes, the number of years lived free of, and the number of years lived with diabetes for the Australian adult population from the year 2000, and to project prevalence of diabetes to the year 2025. Methods: Multi-state life-tables were constructed to simulate the progress of a cohort of 25-year-old Australians. National mortality rates were combined with incidence rates of diabetes and the RR of mortality in people with diabetes derived from the Australian Diabetes, Obesity and Lifestyle study (a national, population-based study of 11,247 adults aged ≥25 years). Results: If the rates of mortality and diabetes incidence observed over the period 2000-2005 continue, 38.0% (95% uncertainty interval 36.6-38.9) of 25-year-olds would be expected to develop diabetes at some time throughout their life. On average, a 25-year-old Australian will live a further 56 years, 48 of these free of diabetes. On average, a 45-year-old person with diabetes can expect to live 6 years less than a person free of diabetes. The prevalence of diabetes is projected to rise from 7.6% in 2000 to 11.4% by 2025. Conclusions/interpretation: If we maintain current diabetes incidence rates, more than a third of individuals will develop diabetes within their lifetime and in Australia there will an additional 1 million cases of diabetes by the year 2025.

Susceptibility of human mesenchymal stem cells to tacrolimus, mycophenolic acid, and rapamycin (Article)

2008-11-15T00:00:00Z

BACKGROUND.: Mesenchymal stem cells (MSC) have multilineage differentiation and immunomodulatory capacities and are potentially useful for therapeutic applications, such as tissue regeneration and control of alloreactivity. MSC are present in most tissues including the transplantable organs. It is therefore unavoidable that MSC will be exposed to immunosuppressive drugs in a clinical transplantation setting. The molecular targets of these drugs are expressed in MSC, but the effect of their inhibition on MSC functioning is unknown. METHODS.: MSC were isolated and expanded from heart tissue and the effects of the calcineurin inhibitor tacrolimus, the cell cycle inhibitor mycophenolic acid (MPA), and the mammalian target of rapamycin inhibitor on MSC survival, proliferation, differentiation, and immunosuppressive capacity were examined. RESULTS.: Short-term exposure to the immunosuppressants did not induce toxicity or apoptosis in MSC, but high-dose tacrolimus induced toxicity after 7 days. MPA and rapamycin inhibited MSC proliferation at therapeutic doses. The immunosuppressants had differential effects on the differentiation capacity of MSC. Tacrolimus reduced the expression of troponin T type 2 and desmin during cardiomyogenic differentiation of MSC, whereas MPA decreased the deposition of calcified minerals during osteogenic differentiation. Rapamycin stimulated lipid production during adipogenic differentiation. Unexpectedly, MSC had adverse effects on the immunosuppressive efficacy of tacrolimus and rapamycin. There was no such effect of MSC on the function of MPA. Preincubation of MSC with tacrolimus increased the immunosuppressive capacity of MSC. DISCUSSION.: This study demonstrates that therapeutic concentrations of immunosuppressive drugs affect MSC function. MSC affect the efficacy of immunosuppressive medication. These findings are important for potential clinical use of MSC in combination with immunosuppressants.

The relation between non-occupational physical activity and years lived with and without disability (Article)

2008-09-15T00:00:00Z

Objectives: The effects of non-occupational physical activity were assessed on the number of years lived with and without disability between age 50 and 80 years. Methods: Using the GLOBE study and the Longitudinal Study of Aging, multi-state life tables were constructed yielding the number of years with and without disability between age 50 and 80 years. To obtain life tables by level of physical activity (low, moderate, high), hazard ratios were derived for different physical activity levels per transition (non-disabled to disabled, non-disabled to death, disabled to non-disabled, disabled to death) adjusted for age, sex and confounders. Results: Moderate, compared to low non-occupational physical activity reduced incidence of disability (HR 0.66, 95% CI 0.51 to 0.86), increased recovery (HR 1.95, 95% CI 1.32 to 2.87), and represents a gain of disability-free years and a loss of years with disability (male 3.1 and 1.2; female 4.0 and 2.8 years). Performing high levels of non-occupational physical activity further reduced incidence, and showed a higher gain in disability-free years (male 4.1; female 4.7), but a similar reduction in years with disability. Conclusion: Among 50–80-year-olds promoting physical activity is a fundamental factor to achieve healthy ageing. In 2025 1.2 billion people worldwide will be aged 60 years and over.1 Living longer is a societal achievement, but also a source of concern as prevalence of major chronic diseases and disability increase with age. A rising share of older age groups in the population will increase the burden of morbidity and will put an upward pressure on costs. The number of older people with severe disability may be 40% to 75% higher by 2030 because of population ageing.2 Health and long-term care spending is projected to almost double by 2050 across members of the Organization of Economic Cooperation and Development (OECD). In the approach of "healthy" ageing, however, these consequences might be mitigated. Physical activity is an important candidate tool to achieve healthy ageing. Physical activity reduces mortality,3 extends life expectancy4 and delays the onset of chronic diseases, including cardiovascular disease (CVD), cancer and diabetes.3–5 Increasing evidence exists that physical activity also delays the onset of disability,6–22 and increases the chances8 15 22–24 and duration of recovery from disability.23 Although an active lifestyle has been found to increase life expectancy in some studies and to reduce disability in others, its overall effect on health is still largely unknown. There are limited data about the effects of physical activity on the number of years with and without disability and these effects are not easy to predict. The effects of risk factors for both disability and death, such as physical activity, can follow different directions.25 Therefore, it is unclear whether the extra years gained by engaging in a physically active lifestyle will be free of disability or will add to the time lived with disability. The aim of this study is to assess the effects of non-occupational physical activity on life expectancy and the number of years lived with and without disability in 50–80-year-olds.

Human heart, spleen, and perirenal fat-derived mesenchymal stem cells have immunomodulatory capacities (Article)

2007-08-01T00:00:00Z

Mesenchymal stem cells (MSCs) have important tissue repair functions and show potent immunosuppressive capacities in vitro. Although usually isolated from the bone marrow, MSCs have been identified in other tissues, including the skin and liver. In the present study, we isolated and characterized MSCs from human heart, spleen, and perirenal adipose tissue. MSCs from these different tissue sites were similar to those derived from bone marrow in that they expressed comparable levels of the cell-surface markers CD90, CD105, CD166, and HLA class I, were negative for CD34, CD45, HLA class II, CD80, and CD86 expression, and were capable of osteogenic and adipogenic differentiation. Like bone marrow-derived MSCs, MSCs from these different tissue sources inhibited the proliferation of alloactivated peripheral blood mononuclear cells (PBMCs), giving 85%, 79%, 79%, and 81% inhibition, respectively. Also in line with bone marrow-derived MSCs they inhibited proliferative responses of PBMCs to phytohemagglutinin, a nonspecific stimulator of lymphocyte proliferation, and reduced-memory T lymphocyte responses to tetanus toxoid. The results of this study demonstrate that MSCs from various tissues have similar immunophenotypes, in vitro immunosuppressive properties, and differentiation potential.

Interleukin-21: An interleukin-2 dependent player in rejection processes (Article)

2007-06-01T00:00:00Z

BACKGROUND. Interleukin (IL)-21 is the most recently described cytokine that signals via the common cytokine receptor (γc), is produced by activated CD4+ T-cells, and regulates expansion and effector function of CD8+ T-cells. MATERIALS. To explore the actions of IL-21 with other γc-dependent cytokines in alloreactivity, mRNA expression of IL-21, IL-21R α-chain, and IL-2 proliferation and cytotoxicity was measured after stimulation in mixed lymphocyte reactions. Additionally, IL-21 and IL-21R α-chain expression was studied in biopsies of heart transplant patients. RESULTS. Analysis of mRNA expression levels of allostimulated T-cells showed a 10-fold induction of IL-21 and IL-21R α-chain. Interestingly, induction of IL-21 was highly dependent on IL-2 (as in the presence of anti-IL-2, anti-IL-2R α-chain, and the immunosuppressive drugs cyclosporine A, tacrolimus, and rapamycin) the transcription of IL-21 was almost completely inhibited, whereas in the presence of exogenous IL-2 the mRNA expression of IL-21 was even more upregulated. IL-21 functioned as a costimulator for IL-2 to augment proliferation and cytotoxic responses, while blockade of the IL-2 route abrogated these functions of IL-21. Blockade of the IL-21 route by anti-IL-21R α-chain monoclonal antibodies inhibited the proliferation of alloactivated T-cells. Also, in vivo alloreactivity was associated with IL-21/IL-21R α-chain expression. After heart transplantation, the highest intragraft IL-21, IL-21R α-chain, and IL-2 mRNA expression levels were measured during acute rejection (P<0.001, P=0.01, P=0.03). CONCLUSION. IL-21 is a critical cytokine for IL-2 dependent immune processes. Blockade of the IL-21 pathway may provide a new perspective for the treatment of allogeneic responses in patients after transplantation.

Primary prevention of cardiovascular disease: Cost-effectiveness comparison (Article)

2007-01-01T00:00:00Z

Objectives: The aim of this study was to evaluate the cost-effectiveness of four risk-lowering interventions (smoking cessation, antihypertensives, aspirin, and statins) in primary prevention of cardiovascular disease. Methods: Using data from the Framingham Heart Study and the Framingham Offspring study, we built life tables to model the benefits of the selected interventions. Participants were classified by age and level of risk of coronary heart disease. The effects of risk reduction are obtained as numbers of death averted and life-years saved within a 10-year period. Estimates of risk reduction by the interventions were obtained from meta-analyses and costs from Dutch sources. Results: The most cost-effective is smoking cessation therapy, representing savings in all situations. Aspirin is the second most cost-effective (€2,263 to €16,949 per year of life saved) followed by antihypertensives. Statins are the least cost-effective (€73,971 to €190,276 per year of life saved). Conclusions: A cost-effective strategy should offer smoking cessation for smokers and aspirin for moderate and high levels of risk among men 45 years of age and older. Statin therapy is the most expensive option in primary prevention at levels of 10-year coronary heart disease risk below 30 percent and should not constitute the first choice of treatment in these populations. Copyright

Physical activity and life expectancy with and without diabetes: life table analysis of the Framingham Heart Study (Article)

2006-01-01T00:00:00Z

OBJECTIVE: Physical activity is associated with a reduced risk of developing diabetes and with reduced mortality among diabetic patients. However, the effects of physical activity on the number of years lived with and without diabetes are unclear. Our aim is to calculate the differences in life expectancy with and without type 2 diabetes associated with different levels of physical activity. RESEARCH DESIGN AND METHODS: Using data from the Framingham Heart Study, we constructed multistate life tables starting at age 50 years for men and women. Transition rates by level of physical activity were derived for three transitions: nondiabetic to death, nondiabetic to diabetes, and diabetes to death. We used hazard ratios associated with different physical activity levels after adjustment for age, sex, and potential confounders. RESULTS: For men and women with moderate physical activity, life expectancy without diabetes at age 50 years was 2.3 (95% CI 1.2-3.4) years longer than for subjects in the low physical activity group. For men and women with high physical activity, these differences were 4.2 (2.9-5.5) and 4.0 (2.8-5.1) years, respectively. Life expectancy with diabetes was 0.5 (-1.0 to 0.0) and 0.6 (-1.1 to -0.1) years less for moderately active men and women compared with their sedentary counterparts. For high activity, these differences were 0.1 (-0.7 to 0.5) and 0.2 (-0.8 to 0.3) years, respectively. CONCLUSIONS: Moderately and highly active people have a longer total life expectancy and live more years free of diabetes than their sedentary counterparts but do not spend more years with diabetes.

Blood pressure in adulthood and life expectancy with cardiovascular disease in men and women: life course analysis. (Article)

2005-08-01T00:00:00Z

Limited information exists about the consequences of hypertension during adulthood on residual life expectancy with cardiovascular disease. We aimed to analyze the life course of people with high blood pressure levels at age 50 in terms of total life expectancy and life expectancy with and without cardiovascular disease compared with normotensives. We constructed multistate life tables for cardiovascular disease, myocardial infarction, and stroke using data from 3128 participants of the Framingham Heart Study who had their 50th birthday while enrolled in the study. For the life table calculations, we used hazard ratios for 3 transitions (healthy to death, healthy to disease, and disease to death) by categories of blood pressure level and adjusted by age, sex, and confounders. Irrespective of sex, 50-year-old hypertensives compared with normotensives had a shorter life expectancy, a shorter life expectancy free of cardiovascular disease, myocardial infarction, and stroke, and a longer life expectancy lived with these diseases. Normotensive men (22% of men) survived 7.2 years (95% confidence interval, 5.6 to 9.0) longer without cardiovascular disease compared with hypertensives and spent 2.1 (0.9 to 3.4) fewer years of life with cardiovascular disease. Similar differences were observed in women. Compared with hypertensives, total life expectancy was 5.1 and 4.9 years longer for normotensive men and women, respectively. Increased blood pressure in adulthood is associated with large reductions in life expectancy and more years lived with cardiovascular disease. This effect is larger than estimated previously and affects both sexes similarly. Our findings underline the tremendous importance of preventing high blood pressure and its consequences in the population.

Relation between trends in late middle age mortality and trends in old age mortality--is there evidence for mortality selection? (Article)

2005-01-01T00:00:00Z

STUDY OBJECTIVE: To test whether mortality selection was a dominant factor in determining trends in old age mortality, by empirically studying the existence of a negative correlation between trends in late middle age mortality and trends in old age mortality among the same cohorts. DESIGN AND METHODS: A cohort approach was applied to period data on total and cause specific mortality for Denmark, England and Wales, Finland, France, the Netherlands, Norway, and Sweden, in 1950-1999. The study described and correlated mortality trends for five year centralised cohorts from 1895 to 1910 at ages 55-69, with the trends for the same cohorts at ages 80-89. The research distinguished between circulatory diseases, cancers, and diseases specifically related to old age. MAIN RESULTS: All cause mortality changes at ages 80-89 were strongly positively correlated with all cause mortality changes at ages 55-69, especially among men, and in all countries. Virtually the same correlations were seen between all cause mortality changes at ages 80-89 and changes in circulatory disease mortality at ages 55-69. Trends in mortality at ages 80-89 from infectious diseases, pneumonia, diabetes mellitus, symptoms, or external causes showed no clear negative correlations with all cause mortality trends at ages 55-69. CONCLUSIONS: The consistently positive correlations seen in this study suggest that trends in old age mortality in north western Europe in the late 20th century were determined predominantly by the prolonged effects of exposures carried throughout life, and not by mortality selection.

Adult obesity and the burden of disability throughout life (Article)

2004-01-01T00:00:00Z

OBJECTIVE: To analyze the prevalence of disability throughout life and life expectancy free of disability, associated with obesity at ages 30 to 49 years. RESEARCH METHODS AND PROCEDURES: We used 46 and 20 years of mortality follow-up, respectively, for 3521 Original and 3013 Offspring Framingham Heart Study participants 30 to 49 years and classified as normal weight, overweight, or obese at baseline. Disability measures were available between 36 and 46 years of follow-up for 1352 Original participants and at 20 years of follow-up for 2268 Offspring participants. We measured the odds of disability in the Original cohort after 46 years follow-up, and we estimated life expectancy with and without disability from age 50. Two disability measures were used, one representing limitations with mobility only and the second representing limitations with activities of daily living (ADL). RESULTS: Obesity at ages 30 to 49 years was associated with a 2.01-fold increase in the odds of ADL limitations 46 years later. Nonsmoking adults who were obese between 30 and 49 years lived 5.70 (95% confidence interval, 4.11 to 7.35) (men) and 5.02 (95% confidence interval, 3.36 to 6.61) (women) fewer years free of ADL limitations from age 50 than their normal-weight counterparts. There was no significant difference in the total number of years lived with disability throughout life between those obese or normal weight, due to both higher disability prevalence and higher mortality in the obese population. DISCUSSION: Obesity in adulthood is associated with an increased risk of disability throughout life and a reduction in the length of time spent free of disability, but no substantial change in the length of time spent with disability.

The Polymeal: a more natural, safer, and probably tastier (than the Polypill) strategy to reduce cardiovascular disease by more than 75% (Article)

2004-01-01T00:00:00Z

OBJECTIVE: Although the Polypill concept (proposed in 2003) is promising in terms of benefits for cardiovascular risk management, the potential costs and adverse effects are its main pitfalls. The objective of this study was to identify a tastier and safer alternative to the Polypill: the Polymeal. METHODS: Data on the ingredients of the Polymeal were taken from the literature. The evidence based recipe included wine, fish, dark chocolate, fruits, vegetables, garlic, and almonds. Data from the Framingham heart study and the Framingham offspring study were used to build life tables to model the benefits of the Polymeal in the general population from age 50, assuming multiplicative correlations. RESULTS: Combining the ingredients of the Polymeal would reduce cardiovascular disease events by 76%. For men, taking the Polymeal daily represented an increase in total life expectancy of 6.6 years, an increase in life expectancy free from cardiovascular disease of 9.0 years, and a decrease in life expectancy with cardiovascular disease of 2.4 years. The corresponding differences for women were 4.8, 8.1, and 3.3 years. CONCLUSION: The Polymeal promises to be an effective, non-pharmacological, safe, cheap, and tasty alternative to reduce cardiovascular morbidity and increase life expectancy in the general population.

Deprivation and systematic stroke prevention in general practice: an audit among general practitioners in the Rotterdam region, The Netherlands (Article)

2003-12-01T00:00:00Z

BACKGROUND: To investigate differences in quality of preventive care provided by general practitioners (GPs) to patients at risk of stroke living in deprived and non-deprived neighbourhoods in the Rotterdam region. METHODS: A 'deprivation score' was used to categorize neighbourhoods according to their deprivation status. Data on the process of patient care were collected by means of chart review and interviews with GPs. Cases of stroke (n=188) were retrospectively audited by an expert panel with guideline-based review criteria. To measure differences in quality of patient care between neighbourhoods, deprivation scores were related to scores for sub-optimal care. RESULTS: After adjustment for socio-demographic characteristics, patients in deprived neighbourhoods had an increased risk (OR 1.95 (95% CI: 0.98-3.90)) of having received sub-optimal preventive care if compared with patients in non-deprived neighbourhoods. This excess risk was limited to women (OR 3.57 (95% CI: 1.39-9.16) vs OR 1.01 (95% CI: 0.41-2.48) in men). Adjustment for socio-demographic characteristics and risk factor distribution did not change the OR for women to receive sub-optimal care significantly (OR 3.21 (95% CI: 1.24-8.31)). Sub-optimal care originated mainly from deficiencies in follow-up of treated hypertensive and diabetes patients and evaluation of patients' cardiovascular risk profile. Among treated hypertensive women in deprived neighbourhoods who received sub-optimal care, the mean number of deficiencies related to follow-up was almost double that of the corresponding group in non-deprived neighbourhoods. CONCLUSION: Quality of care to prevent stroke in general practice differs considerably between deprived and non-deprived neighbourhoods. Patients in deprived neighbourhoods, and women in particular, have almost twice the risk of receiving sub-optimal preventive care.

Improvements in treatment of coronary heart disease and cessation of stroke mortality rate decline. (Article)

2003-07-01T00:00:00Z

BACKGROUND AND PURPOSE: Many countries observed rapidly declining stroke mortality rates during 1970-1990, followed by a slowing or a cessation of this decline. This slowing was seen for both sexes and all ages. Here we test the hypothesis that improvements in coronary heart disease (CHD) survival can explain this slowing through an increase in the number of CHD survivors at an increased risk for stroke. METHODS: We created multistate life-table models based on the survival experience of 46 years of follow-up of the Framingham Heart Study cohort. Improvements in survival after CHD were modeled by decreasing mortality rates for those with CHD. We analyzed whether improved CHD survival could result in a >3% increase in annual stroke mortality rates, which would be enough to eliminate the previously observed decline. RESULTS: CHD survival improvements led to an increase in the number of stroke deaths but also a concomitant increase in the total population size. Under no circumstances was there an annual increase in stroke mortality rates approaching 3% for both sexes and for younger and older age groups. CONCLUSIONS: The hypothesis that increases in the numbers of people with CHD, as a consequence of improvements in CHD survival, explain the observed slowing of the stroke mortality rate decline must be rejected. The true explanation is also likely to be a factor that changed markedly around 1990, but with more direct effects on stroke mortality.

Obesity in adulthood and its consequences for life expectancy: a life-table analysis (Article)

2003-01-01T00:00:00Z

BACKGROUND: Overweight and obesity in adulthood are linked to an increased risk for death and disease. Their potential effect on life expectancy and premature death has not yet been described. OBJECTIVE: To analyze reductions in life expectancy and increases in premature death associated with overweight and obesity at 40 years of age. DESIGN: Prospective cohort study. SETTING: The Framingham Heart Study with follow-up from 1948 to 1990. PARTICIPANTS: 3457 Framingham Heart Study participants who were 30 to 49 years of age at baseline. MEASUREMENTS: Mortality rates specific for age and body mass index group (normal weight, overweight, or obese at baseline) were derived within sex and smoking status strata. Life expectancy and the probability of death before 70 years of age were analyzed by using life tables. RESULTS: Large decreases in life expectancy were associated with overweight and obesity. Forty-year-old female nonsmokers lost 3.3 years and 40-year-old male nonsmokers lost 3.1 years of life expectancy because of overweight. Forty-year-old female nonsmokers lost 7.1 years and 40-year-old male nonsmokers lost 5.8 years because of obesity. Obese female smokers lost 7.2 years and obese male smokers lost 6.7 years of life expectancy compared with normal-weight smokers. Obese female smokers lost 13.3 years and obese male smokers lost 13.7 years compared with normal-weight nonsmokers. Body mass index at ages 30 to 49 years predicted mortality after ages 50 to 69 years, even after adjustment for body mass index at age 50 to 69 years. CONCLUSIONS: Obesity and overweight in adulthood are associated with large decreases in life expectancy and increases in early mortality. These decreases are similar to those seen with smoking. Obesity in adulthood is a powerful predictor of death at older ages. Because of the increasing prevalence of obesity, more efficient prevention and treatment should become high priorities in public health.

A cardiovascular life history (Article)

2002-03-01T00:00:00Z

AIMS The objective of this paper is to measure the potential burden of cardiovascular disease within the original Framingham Heart Study cohort by transforming its well-described epidemiological measures into time-based health policy measures, such as life years lost to or lived with the disease. METHODS AND RESULTS We constructed multi-state life tables of the Framingham Heart Study cohort to calculate dwelling times with a history of cardiovascular disease. Age-specific probabilities determined transitions from healthy through disease to death. For this synthetic cohort, from age 50 men (women) live on average 26 (32) years; 20 (26) free of cardiovascular disease. Allowing occupancy of more than one disease state, 50-year-old males (females) live 2 X 9 (1 X 2) years with a history of myocardial infarction, 0 X 93 (1 X 2) with a history of stroke, and 0 X 67 (0 X 93) with congestive heart failure. Having ever suffered acute myocardial infarction, stroke or congestive heart failure, life expectancy is reduced by 9 (13), 12 (15) or 16 (16) years, respectively in 60-year-old men (women). CONCLUSIONS Transforming occurrence probabilities into time-based health measures, the prevalence of cardiovascular disease is remarkable: from age 50, 20% of remaining life expectancy is lived with the disease. Such measures are integral to appropriate health planning and assessment of the potential population health value of various treatment and prevention strategies.