Effect of 35 years beta-adrenergic blockade therapy on autonomic cardiovascular modulation. A case study.

The influence of long duration beta-blockade on autonomic and cardiovascular function remains not completely understood. The aim of this study was to evaluate the effect of long duration beta-adrenergic blockade treatment for hypertension control, on autonomic cardiovascular control in a 78-year-old male patient in relation to population findings. Heart rate variability was determined in the frequency domain (Total power, low frequency power and high frequency power), during baseline (supine and standing) and during 24 hour Holter recording. Results were compared with heart rate and heart rate variability data obtained from a normal healthy male population as a function of age. Circadian rhythm remained present. Heart rate during daytime was lower compared to the population group. None of the heart rate variability parameters were different from the normal population age group. Our results show that after 35 years of beta-blockade treatment, autonomic modulation of cardiac function remains within normal limits for that age group. Blood pressure remained at the higher limits (120-150/60-80 mmHg), but under control.

Age at death from different diseases: the flemish experience during the period 2000-2004.

BACKGROUND: The age at death from different diseases is a good indicator of their relative importance at the population level. METHODS: Use was made of the mortality data provided by the Flemish Community of Belgium on all deaths, WHO ICD-10 coded, for the period 2000-2004. RESULTS: The mean age at death increases with time for nearly all diseases and for both sexes. This increase is highly significant for all-cause mortality. Deaths due to accidents and suicide cause the greatest loss of life expectancy for the individuals concerned. From the disease groups liver cirrhosis, lung and breast cancer have the greatest impact on life expectancy. Women die at higher ages than men for all diseases except lung cancer. They have a highly significantly greater loss of life expectancy due to lung cancer than men. The mean age at death during the period considered increases markedly for breast cancer (p< 0.0001). This suggests an increased efficiency of both treatment and prevention of breast cancer. CONCLUSIONS: Studying the mean age at death from different pathologies is an efficient and rapid way to evaluate the relative importance of different diseases and the changes in the health situation in a given population. Mortality continues to decline in Flanders.

On the sex ratio of all-cause and disease-specific mortality rates worldwide.

The sex ratio of mortality has important social implications but is only rarely considered. Women have lower mortality rates than men. The sex ratio of mortality is cause-specific and differs markedly between populations. Assuming that the genetic differences between the sexes are very similar between populations implies that the differences in the sex ratio cannot be explained by genetic factors. Gender differences in smoking levels exert a strong influence on the sex ratio of lung cancer, total cardiovascular and all-cause mortality. The sex ratio of mortality decreases with age. The mortality rates between the genders are highly significantly correlated (p < 0.0001) both at younger and older age classes, except for lung cancer in the 45-74 y age class. This demonstrates that identical factors influence the mortality rates of both genders, but at a lower level in women.

Trends in pancreatic cancer incidence in nine SEER Cancer Registries, 1973-2002.

BACKGROUND: The evolution of pancreatic cancer incidence in the last three decades in the United States remains unclear. This study was conducted to investigate this problem, using data from the nine registries of the Surveillance, Epidemiology, and End Results (SEER) Program. PATIENTS AND METHODS: The incidence data in 1973-2002 were age standardized to the 2000 USA standard population and analyzed by the joinpoint regression. RESULTS: For the nine registries combined, pancreatic cancer incidence in men significantly decreased by 0.62% per year from 1973 to 2002. Incidence in women increased until 1984 and slowly declined thereafter. A rise in incidence, although not statistically significant, has been noted in young and middle-aged adults (<60 years) since 1994. Changes in incidence over time substantially differed among the nine SEER registries compared. Incidence decreased in most age-, sex-, and race-specific groups of the populations covered in the nine registries during the period examined. Conversely, a statistically significant increase in incidence was observed among women in Hawaii and Iowa and among old adults (> or =60 years) in Seattle and Utah. CONCLUSIONS: Pancreatic cancer incidence significantly decreased from 1973 to 2002 in men and increased until 1984 and then declined slowly in women in the United States.

Differential evolution of mortality between Denmark and Scotland, period 1970 to 1999. A comparison with mortality data from the European Union.

Mortality rates in Denmark and Scotland are high compared to rates of the other countries of the European Union (EU). Moreover, the evolution of mortality between 1970 and 1999 is very different between the two countries. Differences in lifestyle as possible explanations have been explored. Mortality rates from all causes, total cardiovascular, total cancer and lung cancer for both sexes and from female breast cancer were provided by WHO. Food supply data have been obtained from FAO and smoking rates from published data. Risk factor distribution has been obtained from the Monica survey. The initial mortality was high in both countries for all diseases explored, but highest in Scotland. Progressively the mortality rates between Scotland and Denmark have equalized, especially due to a more rapid decrease of mortality in Scotland. The decrease in all-cause mortality, both in Scotland, Denmark and the EU is almost exclusively due to a decrease of non-cancer mortality, especially TCV mortality. In conclusion, changes in smoking habits and in animal (saturated) fat intake, more pronounced in Scotland, offer the best explanation for the observed changes in mortality. Smoking and nutrition appear to be the most important determinants of mortality in industrialized countries.

Trends in obesity and energy supply in the WHO MONICA Project.

OBJECTIVE: To examine the relationship between secular trends in energy supply and body mass index (BMI) among several countries. DESIGN: Aggregate level analyses of annually reported country food data against anthropometric data collected in independent cross-sectional samples from 34 populations in 21 countries from the early 1980s to the mid-1990s. SUBJECTS: Population randomly selected participants aged 35-64 y. MEASUREMENTS: BMI data were obtained from the WHO MONICA Project. Food energy supply data were derived from the Food Balance Sheet of the Food and Agriculture Organization of the United Nations. RESULTS: Mean BMI as well as the prevalence of overweight (BMI > or =25 kg/m2) increased in virtually all Western European countries, Australia, the USA, and China. Decreasing trends in BMI were seen in Central and Eastern European countries. Increasing trends in total energy supply per capita were found in most high-income countries and China while decreasing trends existed in Eastern European countries. Between country differences in temporal trends of total energy supply per capita explained 41% of the variation of trends in mean BMI; the effect was similar upon the prevalence of overweight and obesity. Trends in percent of energy supply from total fat per capita had a slight effect on the trends in mean BMI (+7% increment in R2) when the total energy supply per capita was adjusted for, while energy supply from total sweeteners per capita had no additional effect. CONCLUSION: Increasing energy supply is closely associated with the increase of overweight and obesity in western countries. This emphasizes the importance of dietary issues when coping with the obesity epidemic.

Epidemiology: past, present and future.

Epidemiology in the past was concerned essentially by the study of infectious diseases which were the cause of huge mortalities especially since urbanisation was initiated. Epidemics of pest, typhus, cholera, influenza a.o. were common. The epidemics were halted by better hygiene, vaccination and antibiotics. Since the second world war epidemiology was dominated by an "epidemic" of new chronic diseases, especially heart disease and cancer. This was due to an increase in life span and to an increase in smoking habits and in the intake of saturated fat and a too small intake of fruit and vegetables combined with a too high intake of salt (NaCl). Gradually epidemiology evolved as the study of the causes, the distribution, the risk factors and the prevention of chronic diseases, but also including accidents, suicide, depression a.o., diseases with a mass occurrence at the population level. The importance of nutrition as a determinant of health gradually became recognized, but remains undervalued by the medical profession. Mortality at the population level follows some simple mathematical laws and can be represented accurately (r2>0.99) between the ages of 35 and 84 year by either Gompertz equations (ln mortality versus age) or by a polynomial equation (ln mortality versus age, age2). This is valid for all populations and both sexes and remains valid at times of great and rapid changes in mortality. This shows that measures for prevention should be directed towards the total population. The future of epidemiology should be directed towards the slowing of the ageing process at the population level by a healthy life style consisting of: not smoking, avoiding obesity, a fair amount of physical activity and a healthy nutrition i.e little salt, little saturated fat, an adequate amount of omega-3 fatty acids and a large amount of fruit and vegetables, with an occasional glass of red wine. This contains the secret of a long and healthy life. Conceptually it will be important to determine whether a maximum human life span, genetically determined, exists. A maximal rectangularization of the mortality curve should then be the ultimate goal. At the same time the possible re-emergence of old and new infectious diseases (SARS, Ebola, BSE, AIDS) should be kept in mind.

INTERMAP: background, aims, design, methods, and descriptive statistics (nondietary).

Blood pressure (BP) above optimal (< or =120/< or =80 mmHg) is established as a major cardiovascular disease (CVD) risk factor. Prevalence of adverse BP is high in most adult populations; until recently research has been sparse on reasons for this. Since the 1980s, epidemiologic studies confirmed that salt, alcohol intake, and body mass relate directly to BP; dietary potassium, inversely. Several other nutrients also probably influence BP. The DASH feeding trials demonstrated that with the multiple modifications in the DASH combination diet, SBP/DBP (SBP: systolic blood pressure, DBP: diastolic blood pressure) was sizably reduced, independent of calorie balance, alcohol intake, and BP reduction with decreased dietary salt. A key challenge for research is to elucidate specific nutrients accounting for this effect. The general aim of the study was to clarify influences of multiple nutrients on SBP/DBP of individuals over and above effects of Na, K, alcohol, and body mass. Specific aims were, in a cross-sectional epidemiologic study of 4680 men and women aged 40-59 years from 17 diverse population samples in China, Japan, UK, and USA, test 10 prior hypotheses on relations of macronutrients to SBP/DBP and on role of dietary factors in inverse associations of education with BP; test four related subgroup hypotheses; explore associations with SBP/DBP of multiple other nutrients, urinary metabolites, and foods. For these purposes, for all 4680 participants, with standardized high-quality methods, assess individual intake of 76 nutrients from four 24-h dietary recalls/person; measure in two timed 24-h urine collections/person 24-h excretion of Na, K, Ca, Mg, creatinine, amino acids; microalbuminuria; multiple nutrients and metabolites by nuclear magnetic resonance and high-pressure liquid chromatography. Based on eight SBP/DBP measurements/person, and data on multiple possible confounders, utilize mainly multiple linear regression and quantile analyses to test prior hypotheses and explore relations of multiple dietary and urinary variables to SBP/DBP of individuals. The 4680 INTERMAP participants are equally divided across four age/gender strata: diverse in ethnicity, education, occupation, physical activity; use of cigarettes, alcohol; diagnosed high BP, CVD, diabetes; CVD family history; women vary in parity, use of contraceptive medication and hormone replacement therapy.

Higher blood pressure in middle-aged American adults with less education-role of multiple dietary factors: the INTERMAP study.

Extensive evidence exists that an inverse relation between education and blood pressure prevails in many adult populations, but little research has been carried out on reasons for this finding. A prior goal of the INTERMAP Study was to investigate this phenomenon further, and to assess the role of dietary factors in accounting for it. Of the 4680 men and women aged 40-59 years, from 17 diverse population samples in Japan, People's Republic of China, UK, and USA, a strong significant inverse education-BP relation was manifest particularly for the 2195 USA participants, independent of ethnicity. With participants stratified by years of education, and assessment of 100+ dietary variables from four 24-h dietary recalls and two 24-h urine collections/person, graded relationships were found between education and intake of many macro- and micronutrients, electrolytes, fibre, and body mass index (BMI). In multiple linear regression analyses with systolic BP (SBP) and diastolic BP (DBP) of individuals the dependent variables (controlled for ethnicity, other possible nondietary confounders), BMI markedly reduced size of education-BP relations, more so for women than for men. Several nutrients considered singly further decreased size of this association by > or =10%: urinary 24-h Na and K excretion, Keys dietary lipid score, vegetable protein, fibre, vitamins C and B6, thiamin, riboflavin, folate, calcium, magnesium, and iron. Combinations of these dietary variables and BMI attenuated the education-SBP inverse coefficient by 54-58%, and the education-DBP inverse coefficient by 59-67%, with over half these effects attributable to specific nutrients (independent of BMI). As a result, the inverse education-BP coefficients ceased to be statistically significant. Multiple specific dietary factors together with body mass largely account for the more adverse BP levels of less educated than more educated Americans. Special efforts to improve eating patterns of less educated strata can contribute importantly to overcoming this and related health disparities in the population.

On the relationship between human all-cause mortality and age.

Many equations can be used to study the relationship between mortality rates and age: Gompertz, Weibull, logistic, polynomial and age-period-cohort equations a.o. All these equations result in highly significant correlations between ln mortality rates and age in the age range 35-84 years. This applies to all developed countries and is independent of the differences in causes of death between populations. The best fit is obtained by a second-degree polynomial equation (R2 > 0.99), closely followed by the Gompertz equation. This equation is preferred in view of its extreme simplicity. A highly significant correlation exists between the intercept and the slope of the Gompertz equations, pointing to a crossing-over age. Beyond that age, around 85 years, populations with high mortality rates have a lower mortality, due to selective survival of the strongest individuals. The polynomial age 2 term may be positive or negative, an expression of the acceleration or de-acceleration of mortality at higher ages and is significantly more often positive in women. The equations used are very useful for the study of the aging process and for examining the relationship between possible causal factors and mortality rates in populations.

Evolution of all-causes and cardiovascular mortality in the age-group 75-84 years in Europe during the period 1970-1996; a comparison with worldwide changes.

BACKGROUND: In spite of the increase in longevity in the past century, studies of mortality patterns in elderly populations are scarce. We investigated cardiovascular and all-cause mortality patterns in age-group 75-84 years in Europe in the period 1970-1996. Methods Mortality data for the age-group 75-84 years were obtained from WHO and standardized according to the old European population standard. Tables were produced showing mortality rates per country around the year 1995 and trends were calculated over the period 1970-1996 using linear regression analysis. Results In both men and women aged 75-84 all-cause and cardiovascular mortality rates were higher in Central and Eastern Europe compared with Western Europe. For the last 3 available years, all-cause mortality rates differed by a factor 2/2.5 (men, women) when comparing the country with the highest with that of the lowest rate. For total cardiovascular mortality this factor was about 4/5 (men, women). During the period 1970-1996, all-cause and total cardiovascular mortality rates declined in most European countries. The decline in all causes of mortality was almost exclusively due to a decline in total cardiovascular disease mortality, especially stroke. Increases in total cardiovascular mortality were observed in some central European countries and Greece. CONCLUSION: Major changes, mainly a decline, occurred in all-cause and cardiovascular mortality in subjects aged 75-84 in Europe. Therefore a passive attitude to health problems in the elderly is not warranted.

Alcohol drinkers overreport their energy intake in the BIRNH study: evaluation by 24-hour urinary excretion of cations. Belgian Interuniversity Research on Nutrition and Health.

OBJECTIVE: Alcohol drinkers are generally considered to underreport their alcohol intake, but little is known about whether they correctly report their energy intake (EI). We assessed the validity of the reported energy intake of alcohol drinkers using the 24-hour urinary (U) excretion of potassium (K) and sodium (Na) as biomarkers. METHODS: A total of 2,124 men and 1,998 women 25 to 74 years of age with a 24-hour urine collection, a random sample of the Belgian Interuniversity Research on Nutrition and Health (BIRNH). were studied. Dietary intake (D), including alcohol consumption, was assessed by a one-day food record. Basal metabolic rate (BMR) was predicted from age, gender and weight. As a measure for the degree of reporting error, D-K/U-K, D-Na/U-Na, EI/U-K, Non-alcohol EI/U-Na (NAEI/U-Na), EI/U-Na, EI/U-creatinine and EI/BMR ratios were calculated and compared among non-, moderate and heavy drinkers in both genders. RESULTS: EI, NAEI and all seven ratios examined generally increased with the level of alcohol intake in both genders. After adjustment for age, body mass index, smoking and educational level, most ratios were significantly higher in moderate drinkers (p < 0.02 to p < 0.0001) and in heavy drinkers (all p < 0.0001) than in non-drinkers. These differences were most significant in male heavy drinkers. The exceptions were D-K/U-K, D-Na/U-Na and NAEI/U-Na in moderate and female heavy drinkers and EI/U-K in male moderate drinkers. The estimated amount of the overreporting of EI by heavy drinkers was 27.8% in men and 13.7% in women. CONCLUSIONS: This study provides evidence that EI and NAEI obtained from the BIRNH study was overreported among alcohol drinkers, especially among male heavy drinkers. It also indicates that EI from alcohol replaced EI from food.

All-cause and cardiovascular mortality worldwide: lessons from geopathology.

Highly significant age-specific differences in all-cause and cardiovascular mortality rates are reported throughout the world. Male mortality is always higher than female mortality, but the sex ratio of mortality rates decreases with age. In most Western countries, all-cause mortality rates have been decreasing during the last 25 years. This decrease is almost uniquely due to a decrease in cardiovascular mortality. It is of crucial importance to try to determine the causes of these differences in mortality at the population level. Many factors may influence mortality: the level of medical care, genetic factors, nutrition, smoking habits, pollution, stress, socioeconomic factors, level of physical activity, etc. Of all the factors considered, nutritional habits and smoking combined with a high saturated fat intake appear to offer the most logical explanation for the existing differences in mortality. The intake of saturated fat has been linked to both cardiovascular and cancer mortality. Based on the modifications in the intercept and slope of the regression lines derived from the Gompertz equation (log mortality versus age) applied to a given population at a specific time, it has been possible to show that nutritional factors influence the aging process. The Gompertz equations point to the existence of a maximum age for the human race. Caution should be exercised when extrapolating population findings to individual subjects, in whom specific factors, e.g., genetic factors, may prevail.

Epidemiology of cancer mortality.

The level in each sex of site-specific cancers mortality is highly variable among 40 countries worldwide and somewhat less in the EU. The mortality ratio of the country worldwide with the highest upon that of the lowest cancer rate varied from 6 to 24 times in men and 6 to 17 times in women. In the EU it ranked from 3 to 10 in men and from 2 to 9 in women. Total cancer mortality had a smaller ratio (2 to 4) suggesting external and/or internal feedback mechanisms. The changes in site-specific cancer mortality rates worldwide over the years are also markedly different. A decreasing pattern since 1980 is more frequent in stomach and rectum cancer rates in each sex, in male lung cancer and in endometrium cancer. An increasing pattern is more often seen in prostate cancer, breast cancer, female lung cancer and male colon cancer. The most significant positive correlations of cardiovascular diseases are observed with rectum cancer in each sex and with endometrium cancer. Only male lung cancer correlates significantly with cardiovascular diseases. Prostate, breast and colon cancer are not positively and significantly related to cardiovascular diseases. The comparison of cancer mortality data from Belgium, The Netherlands and Denmark between 1955 and 1993 are consistent with previous results. The reliability of cancer mortality data and the role of genetic and environmental factors are discussed in two addenda. Finally it can be concluded that colon and rectum cancer behave differently at the population level. Colorectal cancer mortality data will provide misleading epidemiological results.

Blood pressure and urinary cations in a low-fat intake Chinese population sample.

BACKGROUND: The relationship between cation intake and blood pressure (BP) in populations with specific dietary habits such as a low fat intake, remains unclear. A low fat intake has been prevalent during human evolution. METHODS: The average of 6 BP readings and heart rate (HR) recordings has been calculated. Dietary intake was measured using the 24 h recall-method. A 24 h urine sample was collected. RESULTS: A highly significant correlation was found between the sodium/potassium ratio (Na/K), after adjustment for age, weight, height, heart rate, alcohol intake and sex and systolic blood pressure (SBP), diastolic blood pressure (DBP) and pulse pressure (PP). The same applies to the sodium/creatinine (Na/Cr) and potassium/creatinine (K/Cr) ratios, with a positive correlation for Na/Cr and a negative one for K/Cr. The partial regression coefficient was in absolute value about 4-5 times greater for K/Cr than for Na/Cr. Age correlates highly significantly and independently with both SBP and DBP. CONCLUSION: If a Na/K ratio of 1 is considered optimal, by achieving that goal mean SBP could be reduced by about 6 mm Hg and mean DBP by 3 mm Hg in this normotensive population.

Haptoglobin polymorphism as a risk factor for coronary heart disease mortality.

OBJECTIVES: the aim of our study was to evaluate the independent role of the haptoglobin (Hp) polymorphism as a risk factor for coronary heart disease (CHD) mortality. METHODS: within the framework of the longitudinal part of the Belgian Interuniversity Research on Nutrition and Health (BIRNH) survey, a nested case-control study design was performed through matching the 107 deaths from CHD, occurring within a 10-year follow-up period, with three controls for age and gender. RESULTS: the distribution of the Hp types was found to be in Hardy-Weinberg equilibrium. Conditional logistic regression analysis for matched sets revealed that the Hp polymorphism was significantly associated with CHD death. Rather surprisingly, the finding was that Hp 1-1 individuals were at doubled risk for CHD mortality compared with the others, the odds ratio being 2.09 (95% CI: 1.22-3.60). The association was independent from other classical cardiovascular risk factors and the Hp concentration, and of comparable magnitude between men and women. Moreover, evaluating the interaction term in a multiplicative model showed that the Hp type did not play a synergistic role in the prognostic value of established cardiovascular risk factors. CONCLUSION: in contrast to the findings from cross-sectionally based studies, the results from this longitudinal study show that Hp 1-1 individuals are at elevated risk for CHD mortality.

Queen Margrethe II and mortality in Danish women.

All-cause mortality in women is declining in all western European countries, apart from in Danish women. All-cause mortality in Danish women, age-adjusted to 45-74 years was compared with all-cause mortality in women in Scotland and with the mean of the other countries of the European Union for 1970-96. The decline of all-cause mortality in Danish women stopped in 1978 whereas the decline continued in Scotland. In 1996, all-cause mortality was 48% higher in Denmark than that of the mean for the European Union countries. Many Danish women are smokers. Halting of the decline in mortality occurred about 5 years after the ascension to the throne of Denmark by Queen Margrethe II. The queen is very popular in Denmark and a known cigarette smoker. As a role model for women, the Queen's example could offer an explanation for the unusual mortality in Danish women.