Relation of urinary calcium and magnesium excretion to blood pressure: The International Study Of Macro- And Micro-nutrients And Blood Pressure and The International Cooperative Study On Salt, Other Factors, And Blood Pressure.

Data indicate an inverse association between dietary calcium and magnesium intakes and blood pressure (BP); however, much less is known about associations between urinary calcium and magnesium excretion and BP in general populations. The authors assessed the relation of BP to 24-hour excretion of calcium and magnesium in 2 cross-sectional studies. The International Study of Macro- and Micro-Nutrients and Blood Pressure (INTERMAP) comprised 4,679 persons aged 40-59 years from 17 population samples in China, Japan, the United Kingdom, and the United States, and the International Cooperative Study on Salt, Other Factors, and Blood Pressure (INTERSALT) comprised 10,067 persons aged 20-59 years from 52 samples around the world. Timed 24-hour urine collections, BP measurements, and nutrient data from four 24-hour dietary recalls (INTERMAP) were collected. In multiple linear regression analyses, urinary calcium excretion was directly associated with BP. After adjustment for multiple confounders (including weight, height, alcohol intake, calcium intake, urinary sodium level, and urinary potassium intake), systolic BP was 1.9 mm Hg higher per each 4.1 mmol per 24 hours (2 standard deviations) of higher urinary calcium excretion (associations were smaller for diastolic BP) in INTERMAP. Qualitatively similar associations were observed in INTERSALT analyses. Associations between magnesium excretion and BP were small and nonsignificant for most of the models examined. The present data suggest that altered calcium homoeostasis, as exhibited by increased calcium excretion, is associated with higher BP levels.

Metabolome-wide association study identifies multiple biomarkers that discriminate north and south Chinese populations at differing risks of cardiovascular disease: INTERMAP study.

Rates of heart disease and stroke vary markedly between north and south China. A (1)H NMR spectroscopy-based metabolome-wide association approach was used to identify urinary metabolites that discriminate between southern and northern Chinese population samples, to investigate population biomarkers that might relate to the difference in cardiovascular disease risk. NMR spectra were acquired from two 24-h urine specimens per person for 523 northern and 244 southern Chinese participants in the INTERMAP Study of macro/micronutrients and blood pressure. Discriminating metabolites were identified using orthogonal partial least squares discriminant analysis and assessed for statistical significance with conservative family wise error rate < 0.01 to minimize false positive findings. Urinary metabolites significantly (P < 1.2 × 10(-16) to 2.9 × 10(-69)) higher in northern than southern Chinese populations included dimethylglycine, alanine, lactate, branched-chain amino acids (isoleucine, leucine, valine), N-acetyls of glycoprotein fragments (including uromodulin), N-acetyl neuraminic acid, pentanoic/heptanoic acid, and methylguanidine; metabolites significantly (P < 1.1 × 10(-12) to 2 × 10(-127)) higher in the south were gut microbial cometabolites (hippurate, 4-cresyl sulfate, phenylacetylglutamine, 2-hydroxyisobutyrate), succinate, creatine, scyllo-inositol, prolinebetaine, and trans-aconitate. These findings indicate the importance of environmental influences (e.g., diet), endogenous metabolism, and mammalian-gut microbial cometabolism, which may help explain north-south China differences in cardiovascular disease risk.

Dietary sources of sodium in China, Japan, the United Kingdom, and the United States, women and men aged 40 to 59 years: the INTERMAP study.

Public health campaigns in several countries encourage population-wide reduced sodium (salt) intake, but excessive intake remains a major problem. Excessive sodium intake is independently related to adverse blood pressure and is a key factor in the epidemic of prehypertension/hypertension. Identification of food sources of sodium in modern diets is critical to effective reduction of sodium intake worldwide. We used data from the INTERMAP Study to define major food sources of sodium in diverse East Asian and Western population samples. INTERMAP is an international, cross-sectional, epidemiologic study of 4, 680 individuals ages 40 to 59 years from Japan (four samples), People's Republic of China (three rural samples), the United Kingdom (two samples), and the United States (eight samples); four in-depth, multipass 24-hour dietary recalls/person were used to identify foods accounting for most dietary sodium intake. In the People's Republic of China sample, most (76%) dietary sodium was from salt added in home cooking, about 50% less in southern than northern samples. In Japan, most (63%) dietary sodium came from soy sauce (20%), commercially processed fish/seafood (15%), salted soups (15%), and preserved vegetables (13%). Processed foods, including breads/cereals/grains, contributed heavily to sodium intake in the United Kingdom (95%) and the United States (for methodological reasons, underestimated at 71%). To prevent and control prehypertension/hypertension and improve health, efforts to remove excess sodium from diets in rural China should focus on reducing salt in home cooking. To avoid excess sodium intake in Japan, the United Kingdom, and the United States, salt must be reduced in commercially processed foods.

Glutamic acid, the main dietary amino acid, and blood pressure: the INTERMAP Study (International Collaborative Study of Macronutrients, Micronutrients and Blood Pressure).

BACKGROUND: Data are available that indicate an independent inverse relationship of dietary vegetable protein to the blood pressure (BP) of individuals. Here, we assess whether BP is associated with glutamic acid intake (the predominant dietary amino acid, especially in vegetable protein) and with each of 4 other amino acids that are relatively higher in vegetable than animal protein (proline, phenylalanine, serine, and cystine). METHODS AND RESULTS: This was a cross-sectional epidemiological study with 4680 persons 40 to 59 years of age from 17 random population samples in China, Japan, the United Kingdom, and the United States. BP was measured 8 times at 4 visits; dietary data (83 nutrients, 18 amino acids) were obtained from 4 standardized, multipass, 24-hour dietary recalls and 2 timed 24-hour urine collections. Dietary glutamic acid (percentage of total protein intake) was inversely related to BP. Across multivariate regression models (model 1, which controlled for age, gender, and sample, through model 5, which controlled for 16 possible nonnutrient and nutrient confounders), estimated average BP differences associated with a glutamic acid intake that was higher by 4.72% of total dietary protein (2 SD) were -1.5 to -3.0 mm Hg systolic and -1.0 to -1.6 mm Hg diastolic (z scores -2.15 to -5.11). Results were similar for the glutamic acid-BP relationship with each of the other amino acids also in the model; eg, with control for 15 variables plus proline, systolic/diastolic pressure differences were -2.7/-2.0 mm Hg (z scores -2.51, -2.82). In these 2-amino acid models, higher intake (by 2 SD) of each of the other amino acids was associated with small BP differences and z scores. CONCLUSIONS: Dietary glutamic acid may have independent BP-lowering effects, which may contribute to the inverse relation of vegetable protein to BP.

Relationship of dietary linoleic acid to blood pressure. The International Study of Macro-Micronutrients and Blood Pressure Study [corrected].

Findings from observational and interventional studies on the relationship of dietary linoleic acid, the main dietary polyunsaturated fatty acid, with blood pressure have been inconsistent. The International Study of Macro-Micronutrients and Blood Pressure is an international cross-sectional epidemiological study of 4680 men and women ages 40 to 59 years from 17 population samples in China, Japan, United Kingdom, and United States. We report associations of linoleic acid intake of individuals with their blood pressure. Nutrient intake data were based on 4 in-depth multipass 24-hour dietary recalls per person and 2 timed 24-hour urine collections per person. Systolic and diastolic blood pressures were measured 8 times at 4 visits. With several models to control for possible confounders (dietary or other), linear regression analyses showed a nonsignificant inverse relationship of linoleic acid intake (percent kilocalories) to systolic and diastolic blood pressure for all of the participants. When analyzed for 2238 "nonintervened" individuals (not on a special diet, not consuming nutritional supplements, no diagnosed cardiovascular disease or diabetes, and not taking medication for high blood pressure, cardiovascular disease, or diabetes), the relationship was stronger. With adjustment for 14 variables, estimated systolic/diastolic blood pressure differences with 2-SD higher linoleic acid intake (3.77% kcal) were -1.42/-0.91 mm Hg (P<0.05 for both) for nonintervened participants. For total polyunsaturated fatty acid intake, blood pressure differences were -1.42/-0.98 mm Hg (P<0.05 for both) with 2 SD higher intake (4.04% kcal). Dietary linoleic acid intake may contribute to prevention and control of adverse blood pressure levels in general populations.

Human metabolic phenotype diversity and its association with diet and blood pressure.

Metabolic phenotypes are the products of interactions among a variety of factors-dietary, other lifestyle/environmental, gut microbial and genetic. We use a large-scale exploratory analytical approach to investigate metabolic phenotype variation across and within four human populations, based on 1H NMR spectroscopy. Metabolites discriminating across populations are then linked to data for individuals on blood pressure, a major risk factor for coronary heart disease and stroke (leading causes of mortality worldwide). We analyse spectra from two 24-hour urine specimens for each of 4,630 participants from the INTERMAP epidemiological study, involving 17 population samples aged 40-59 in China, Japan, UK and USA. We show that urinary metabolite excretion patterns for East Asian and western population samples, with contrasting diets, diet-related major risk factors, and coronary heart disease/stroke rates, are significantly differentiated (P < 10(-16)), as are Chinese/Japanese metabolic phenotypes, and subgroups with differences in dietary vegetable/animal protein and blood pressure. Among discriminatory metabolites, we quantify four and show association (P < 0.05 to P < 0.0001) of mean 24-hour urinary formate excretion with blood pressure in multiple regression analyses for individuals. Mean 24-hour urinary excretion of alanine (direct) and hippurate (inverse), reflecting diet and gut microbial activities, are also associated with blood pressure of individuals. Metabolic phenotyping applied to high-quality epidemiological data offers the potential to develop an area of aetiopathogenetic knowledge involving discovery of novel biomarkers related to cardiovascular disease risk.

Dietary phosphorus and blood pressure: international study of macro- and micro-nutrients and blood pressure.

Raised blood pressure is a leading cause of morbidity and mortality worldwide; improved nutritional approaches to population-wide prevention are required. Few data are available on dietary phosphorus and blood pressure and none are available on possible combined effects of phosphorus, magnesium, and calcium on blood pressure. The International Study of Macro- and Micro-Nutrients and Blood Pressure is a cross-sectional epidemiologic study of 4680 men and women ages 40 to 59 from 17 population samples in Japan, China, United Kingdom, and United States. Blood pressure was measured 8 times at 4 visits. Dietary intakes were obtained from four 24-hour recalls plus data on supplement use. Dietary phosphorus was inversely associated with blood pressure in a series of predefined multiple regression models, with the successive addition of potential confounders, both nondietary and dietary. Estimated blood pressure differences per 232 mg/1000 kcal (2 SD) of higher dietary phosphorus were -1.1 to -2.3 mm Hg systolic/-0.6 to -1.5 mm Hg diastolic (n=4680) and -1.6 to -3.5 mm Hg systolic/-0.8 to -1.8 mm Hg diastolic for 2238 "nonintervened" individuals, ie, those without special diet/nutritional supplements or diagnosis/treatment for cardiovascular disease or diabetes. Dietary calcium and magnesium, correlated with phosphorus (partial r=0.71 and r=0.68), were inversely associated with blood pressure. Blood pressures were lower by 1.9 to 4.2 mm Hg systolic/1.2 to 2.4 mm Hg diastolic for people with intakes above versus below country-specific medians for all 3 of the minerals. These results indicate the potential for increased phosphorus/mineral intake to lower blood pressure as part of the recommendations for healthier eating patterns for the prevention and control of prehypertension and hypertension.

Patterns and trends of pancreatic cancer mortality rates in Arkansas, 1969-2002: a comparison with the US population.

Little is known about trends in pancreatic cancer mortality in individual states of the US and its whole population. This study aimed to describe the patterns and trends of pancreatic cancer mortality in Arkansas, 1969-2002, using the US national rates as a reference. Joinpoint regression analyses were performed to evaluate trends in age-standardized mortality rates of pancreatic cancer by age group, sex, and race, using data obtained from the National Center for Health Statistics. Throughout the period examined, mortality decreased in young and middle-aged people (<60 years) and men but increased in old people (>/=60 years) and women. A continuous fall in mortality occurred among whites except for a transient rise in the late 1970s. For blacks, mortality rates did not cease to increase until 1995. Unlike in Arkansas, a monotonic upward or downward trend in mortality by age group and sex was not observed in the US. A decline of mortality stopped in 1997 for US whites. Recent decreasing trends were more pronounced in Arkansas blacks than in US blacks. Changes of pancreatic cancer mortality in the last three decades in Arkansas remarkably differed by age, sex, and race and were different in patterns from those of the US population.

Differences in breast cancer mortality worldwide: unsolved problems.

Breast cancer mortality remains a major cause of female mortality. Between 1970 and 2000 both important increases and decreases in breast cancer mortality rates occurred. Large differences in breast cancer mortality exist among countries worldwide. Contradictory findings concerning the role of lifestyle, especially nutrition, remain to be explained. Possible explanations for the observed mortality differences will be explored. Breast cancer mortality rates have been correlated with other causes of mortality; both cancer and noncancer, using data obtained from 47 countries worldwide (World Health Organization). They have also been correlated with dietary data, especially concerning fat (animal and vegetal) intake (Food and Agricultural Organization). Highly significant correlations existed between breast cancer mortality and mortality from other cancers (e.g. colon, stomach) obtained from both sexes. These correlations have been confirmed over a period of more than 40 years. Highly significant positive correlations also existed with the intake of animal (saturated) fat, covering a period of 30 years. In multivariate regression, only the relationship with the colon, prostate cancer and total energy intake remained significant. Ecological data point to nutritional factors, especially animal fat, as major promoters of breast cancer mortality worldwide. This contrasts with the results of most cohort studies. These contradictory results and the relationship between breast cancer mortality and other causes of mortality remain to be explained. More refined and standardized dietary data are necessary.

Association between protein intake and blood pressure: the INTERMAP Study.

BACKGROUND: Findings from epidemiological studies suggest an inverse relationship between individuals' protein intake and their blood pressure. METHODS: Cross-sectional epidemiological study of 4680 persons, aged 40 to 59 years, from 4 countries. Systolic and diastolic blood pressure was measured 8 times at 4 visits. Dietary intake based on 24-hour dietary recalls was recorded 4 times. Information on dietary supplements was noted. Two 24-hour urine samples were obtained per person. RESULTS: There was a significant inverse relationship between vegetable protein intake and blood pressure. After adjusting for confounders, blood pressure differences associated with higher vegetable protein intake of 2.8% kilocalories were -2.14 mm Hg systolic and -1.35 mm Hg diastolic (P<.001 for both); after further adjustment for height and weight, these differences were -1.11 mm Hg systolic (P<.01) and -0.71 mm Hg diastolic (P<.05). For animal protein intake, significant positive blood pressure differences did not persist after adjusting for height and weight. For total protein intake (which had a significant interaction with sex), there was no significant association with blood pressure in women, nor in men after adjusting for dietary confounders. There were significant differences in the amino acid content of the diets of persons with high vegetable and low animal protein intake vs the diets of persons with low vegetable and high animal protein intake. CONCLUSIONS: Vegetable protein intake was inversely related to blood pressure. This finding is consistent with recommendations that a diet high in vegetable products be part of healthy lifestyle for prevention of high blood pressure and related diseases.

Dynamics of cardiovascular and all-cause mortality in Western and Eastern Europe between 1970 and 2000.

AIMS: Important changes in cardiovascular and all-cause mortality rates are occurring in Western and Eastern Europe, each with their own dynamics. Differences in trends will be analysed and possible causes are discussed. METHODS AND RESULTS: Mortality data for cardiovascular and all-cause mortality rates from different countries were obtained from WHO and were analysed for the period 1970-2000. The annual changes in cause-specific mortality rates were calculated using linear and polynomial regression models. Mortality rates declined almost linearly for ischaemic heart disease, stroke, and total cardiovascular diseases between 1970 and 2000 in Western Europe. In both men and women, the decline for these diseases varied between 50 and 65% or approximately 2%/year in this period. In contrast, in Eastern Europe cardiovascular mortality rates reached a maximum in the period 1990-94, followed by a decline of approximately 3%/year in Poland, 2%/year in Hungary, and 5%/year in the Baltic states. The changes in cardiovascular mortality rates were reflected in all-cause mortality rates in both Western and Eastern Europe. CONCLUSION: Over the past 30 years, mortality rates in cardiovascular diseases increased or decreased very rapidly. The causes are complex but changes in diet appear to play a major role. The more recent declines in Western Europe also reflect improvements in modern cardiovascular treatment.

Milk consumption in relation to incidence of prostate, breast, colon, and rectal cancers: is there an independent effect?

Milk contains a wide variety of ingredients, such as nutrients, hormones, and chemical contaminants. Whether milk consumption is associated with the risk of prostate, breast, colon, and rectal cancers is unclear and was evaluated in this study. Data on milk consumption for 9 time periods (1964-1994) and incidence rates of prostate, female breast, colon, and rectal cancers, mostly around 1993-1997, in 38 countries were obtained from the Food and Agriculture Organization and World Health Organization, respectively. Milk consumption was strongly correlated with incidence rates of prostate cancer (r = 0.65-0.69; all P < 0.0001) and breast cancer (r = 0.64-0.74; all P < 0.0001) in all the nine time periods examined. A modest positive correlation was found for colon and rectal cancers in both sexes (all P < 0.05, except for rectal cancer in the first three time periods). The previous findings remained essentially unchanged after adjustment for vegetable, alcohol, and cigarette consumption but disappeared after further adjustment for non-milk fat consumption, except for breast cancer in the last three time periods. The present study does not support an overall substantial effect of milk consumption on the risk of prostate, breast, colon, and rectal cancers at the population level.

On the relationship between all-cause, cardiovascular, cancer and residual mortality rates with age.

BACKGROUND: The existence of a highly significant linear relationship between the natural logarithm (ln) all-cause mortality rate and age at the population level is firmly established (r>0.99). The slope and intercept of the equation, however, vary markedly between populations. Whether this relationship also applies to specific disease entities has not been established. METHODS: Use was made of mortality rates for all-cause, total cardiovascular, total cancer and residual diseases. The midpoint of 5-year age classes between the ages of 35 and 84 years, obtained for both sexes, were analysed. The mean of the three latest available years, from the period 1997-1999 were used. RESULTS: The relationship also applies to a slightly lesser degree to the relationship between total cardiovascular mortality rate, consisting predominantly of ischemic heart disease and stroke, and age (r>0.99). Marginally better relationships are obtained using a second-degree polynomial equation between ln all-cause mortality rate and age, age as independent variables. Total ln cancer mortality rate, however, behaves differently with a significant negative deviation of the mortality rate from linearity at older ages. Residual mortality (non-cancer, non-cardiovascular) mortality shows a mirror pattern to cancer mortality. This residual mortality expressed as a percentage of all-cause mortality varies markedly between populations. The level of some major constituents of the residual mortality rates (respiratory diseases, pneumonia, ill-defined causes and senility) also varies markedly. CONCLUSIONS: The magnitude of the variation suggests misclassification or misdiagnosis of several important disease entities, for example, between senility and stroke or between pneumonia and lung cancer. This questions the validity of disease-specific mortality rates especially at older ages, making their comparison between countries less reliable.

On the sex ratio of mortality: evolution during the period 1970-1999.

In the industrialized world large differences between male and female age-specific mortality rates exist, favouring the female sex.These differences vary over time and depend on the type of disease. This study intends to define the problem by determining the male/female (M/F) ratio of mortality for different disease groups and 2 time periods, 1970 and 1999.