The genesis of the third and fourth heart sounds. A pressure-flow study in dogs.

To examine the mechanism of mitral flow deceleration in diastole and its potential influence on the genesis of third (S3) and fourth (S4) heart sounds, we simultaneously recorded left atrial and left ventricular pressures (micromanometers), mitral flow velocity (electromagnetic catheter-tip flow velocity meter), and internal and external phonocardiograms in 25 open-chest dogs. Diastolic time intervals, transmitral pressure gradients (planimetry), maximum mitral flow velocity, and acceleration and deceleration of flow were measured under different loading conditions. It was found that deceleration of mitral flow in early and late diastole is always caused by a negative transmitral pressure gradient. After volume loading, diastolic pressures, positive (forward) and negative (backward) transmitral pressure gradients, and acceleration and deceleration of flow increased, and an S3 or S4 appeared (20:25 dogs). These sounds occurred during the phase of flow deceleration and could be recorded from the chest wall, inside the left ventricle, and directly from the epicardial surface of the freely exposed left ventricular wall. After balloon occlusion of the inferior vena cava (17:25 dogs), the opposite changes were observed and gallop sounds disappeared. The results indicate that the left ventricular pressure rise in response to filling reverses the transmitral pressure gradient and decelerates flow. Deceleration of inflow by the left ventricular wall in early and late diastole may represent a key mechanism in the genesis of S3 and S4.

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.

Apparent pulse wave velocity in the canine superior vena cava.

In order to evaluate clinically recorded jugular vein pulses it is necessary to understand the transmission process of the right atrial pressure pulse through the caval veins up to the jugular veins. The transmission speed at distinct points of the venous pressure curve was studied in the superior vena cava of 20 anaesthetised dogs. Under control conditions the propagation velocities varied from 1.2 +/- 0.49 to 2.5 +/- 1.36 m . s-1. During increased preload of the heart propagation velocities rose significantly from 2.2 to 4.2 m . s-1 per kPa as a function of mean venous pressure and from 2.3 to 5.8 m . s-1 per kPa as a function of phasic pressures. Right atrial pacing (between 60 and 120 beats . min-1) did not influence the propagation velocity of the studied distinct points. It was found that the summits of the pressure pulse propagate at only a slightly higher speed than the nadirs.

Relationship of serum sodium, potassium, calcium, and phosphorus with blood pressure. Belgian Interuniversity Research on Nutrition and Health.

During an epidemiological survey on the relationship between diet and cardiovascular risk factors, serum sodium, potassium, calcium, phosphorus, and total protein were measured in 4167 men and 3891 women with a mean age of 49 years. Several consistent and highly significant correlations were found between serum cation and phosphorus levels and blood pressure. The analysis was performed separately in the total group and in the group not receiving treatment for hypertension. A highly significant negative correlation existed between serum sodium and both systolic and diastolic blood pressure. Serum potassium correlated negatively with blood pressure only in men. Serum phosphorus correlated negatively in men and women with systolic blood pressure. Serum calcium correlated positively with systolic and diastolic blood pressure in men, but only with diastolic blood pressure in women. All these correlations were independent of serum total protein. A significant negative correlation between serum phosphorus and heart rate and a significant positive correlation between the serum calcium/phosphorus ratio and heart rate were demonstrated.

Relationship of dietary sodium, potassium, calcium, and magnesium with blood pressure. Belgian Interuniversity Research on Nutrition and Health.

From 1979 through 1984, a randomized epidemiological survey in Belgium assessed the dietary intake of sodium, potassium, calcium, and magnesium using 24-hour food records checked by trained dietitians. Dietary cation intake levels were correlated with blood pressure both in the total group (4167 men and 3891 women) and in the group not taking antihypertensive medication (3814 men and 3329 women). Serum sodium, potassium, calcium, and phosphorus were also measured. Multiple regression analysis adjusting for age, body mass index, heart rate, alcohol intake, and total caloric intake revealed a significant positive correlation between sodium intake and blood pressure in the group not treated for hypertension except for diastolic blood pressure in women. A significant negative correlation was found between dietary calcium intake and diastolic blood pressure in men and between dietary magnesium intake and systolic blood pressure in women. No independent effect of dietary potassium intake on blood pressure could be established. Significant but weak correlations were found between the dietary intake of sodium, potassium and calcium and their serum values. The study confirms the hypothesis that at the population level dietary cations are related to the regulation of blood pressure.

Epidemiological study of the relationship between calcium and blood pressure.

During an epidemiological survey of 9321 male Belgian subjects, a highly significant positive correlation was found between the serum calcium level and blood pressure. The slope of the equation relating serum calcium level to blood pressure was higher in subjects who restricted their sodium intake than in subjects who did not. The slope was also significantly higher in subjects who did not take medication for hypertension compared to those who did. There was a significant and positive correlation between urinary calcium measured from 24-hour samples and blood pressure, both in the Belgian study and in a further epidemiological survey in Korea. In the Korean study, no significant correlation was found between 24-hour urinary magnesium excretion and blood pressure.

A survey of blood pressure distribution in Pygmy and Bantu populations in Cameroon.

A blood pressure survey was performed in isolated Pygmy communities and Bantu population samples living either in close relationship with the Pygmies or in separate areas within the same region. The Pygmies are still living as hunter-gatherers, whereas the Bantus rely on agriculture for food provision. Mean blood pressures in Pygmies were 130/85 mm Hg in males and 126/80 mm Hg in females and in Bantus were 137/87 mm Hg in males and 136/84 mm Hg in females. In spot urine the mean urinary sodium concentration was higher in Bantus than Pygmies (86 versus 37 mmol/L in males; 95 versus 56 mmol/L in females). In the total population urinary potassium concentration was very high (150 mmol/L), calcium concentration very low (0.4 mmol/L), and urea concentration low (6.9 g/L). After adjustment for age, height, weight, and sex, no racial differences in blood pressure were present. Blood pressure increased with age but body mass index did not. Diastolic pressure correlated significantly but negatively with urinary sodium in multiple regression analysis. Our study demonstrates that blood pressure increases with age in hunter-gatherer populations on a low to moderately high sodium diet in the presence of a low urinary excretion of calcium coupled with a low protein intake.

The relationship between cations and blood pressure in the People's Republic of China.

Blood pressure was measured in the north and in the south of the People's Republic of China in 1002 men and 1006 women. The 24-hour urinary excretion of sodium, potassium, calcium, magnesium, and creatinine was measured, and the relationship between urinary cations and blood pressure was studied. Blood pressure and 24-hour sodium excretion were higher in northern China than in southern China. With some exceptions, a positive correlation was found between urinary sodium and blood pressure and a negative one between 24-hour urinary potassium excretion and blood pressure. Urinary calcium correlated negatively and urinary magnesium did not correlate significantly with blood pressure. The sodium/potassium ratio correlated positively with blood pressure, and the calcium/magnesium ratio, negatively. This study confirms the positive within-population relationship between sodium intake and blood pressure in Oriental populations.

Findings of the International Cooperative INTERSALT Study.

INTERSALT, an international cooperative study on electrolytes and other factors related to blood pressure, found, in within-population analyses involving 10,079 persons, a significant positive association between 24-hour urinary sodium excretion and systolic blood pressure and between the sodium/potassium ratio and systolic blood pressure. These significant findings were derived from analyses for individuals from all 52 centers and from the 48 centers remaining when persons from four low sodium centers were excluded. Potassium excretion of individuals was significantly and independently related inversely to their systolic blood pressure. For men and women, both separate and combined, the relation between sodium and systolic blood pressure was stronger for older than younger adults, perhaps reflecting the result of longer exposure with age or diminished capacity to handle a sodium load. Relations between electrolyte excretion and diastolic blood pressure in individuals were weaker than for systolic blood pressure. Body mass index and heavy alcohol consumption of individuals were strongly and independently related to blood pressure. In cross-population analyses with n = 52 or n = 48, sample median sodium excretion was significantly and independently related to the slope of systolic blood pressure and diastolic blood pressure with age. Other ecological analyses yielded inconsistent results. Four isolated populations showed low sodium excretion, low sodium/potassium excretion, low body mass index, and low alcohol consumption; sample median blood pressures were low, there was little or no upward slope of blood pressure with age, and high blood pressure was rare or nonexistent.

Value of Food and Agriculture Organization data on food-balance sheets as a data source for dietary fat intake in epidemiologic studies.

The relationships between the per person supply (expressed as percent of total energy supply) of saturated fatty acids (SFAs), monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) obtained from 1979-1981 Food and Agriculture Organization (FAO) data, and the per person intake obtained from 52 individual dietary surveys performed in 19 countries, were examined. In particular, the ratio of PUFAs to SFAs (P:S) and the ratio of unsaturated fatty acids (MUFAs and PUFAs) to SFAs (U:S) obtained from both data sources were examined. Significant correlations (P less than 0.001) were found between the two data sources for the P:S, U:S, SFAs, and MUFAs and PUFAs (P less than 0.02) in 19 countries. It is concluded that the data on fat intake from the FAO are valid for use in epidemiologic studies. In view of the variability of the data, it is recommended to use them either expressed as percentage of energy or as ratios of the different components.

Serum lipid and apolipoprotein levels in a Nigerian population sample.

Serum lipids and apoproteins have been measured in 307 men and 235 women living around Benin City in Nigeria. Total serum cholesterol values are low compared both to White Western populations and to American Blacks. HDL-cholesterol levels, however, are comparable to values in Western and Oriental men, but lower than in Western women. A highly significant correlation exists between total cholesterol and apo B and between HDL-cholesterol and apo A-I in men and women. The low serum lipid values are related to a low dietary fat intake, almost exclusively from palm oil, in the Nigerian 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.

Trends in systolic blood pressure, 24-hour sodium excretion, and stroke mortality in the elderly in Belgium.

Data from six surveys of systolic blood pressure conducted in Belgium between 1967 and 1986 were analyzed. The mean ages of the six groups of 3,328 subjects ranged from 70 to 81 years. The prevalence of systolic blood pressure levels above 159 mm Hg decreased between 1967 and 1986 from 51% to 21% in men and 66% to 22% in women; severe hypertension (systolic blood pressure greater than 220 mm Hg) nearly disappeared. During the same period, body mass index increased 1.1 kg/m2 in men and was unchanged in women; mean systolic blood pressure decreased from 159 to 142 mm Hg in men and from 171 to 147 mm Hg in women; the proportion of subjects receiving treatment for hypertension increased from 10% to 36% in men and from 18% to 41% in women; and the mean standardized 24-hour sodium excretion decreased from 265 to 188 mmol in men and from 208 to 160 mmol in women. Systolic blood pressure levels were significantly and independently related to sodium excretion in the 1967 and 1972 studies. The decrease in systolic blood pressure in Belgium was influenced by the combined effects of more and better treatment for hypertension and a decrease in sodium intake.

Normalized first derivative ofthe left apex cardiogram in assessment of left ventricular function.

The relation between the left displacement apex cardiogram and the left ventricular pressure during isovolumic contraction was studied in 30 patients with cardiac disease. Using the instantaneous relation between the first time derivative and the magnitude of both the left apex cardiogram and the left ventricular pressure, normalized derivatives were obtained. These noramized velocities were correlated with each other and with several indexes of left ventricular function. The normalized derivatives of the left apex cardiogram (dD/dt/D) and the left ventricular pressure (dP/dt/P) were similar in magnitude, standard deviation and variation coefficient. No such similarity was present when the first time derivatives of each tracing (dD/dt and dP/dt) were compared. A highly significant relation was found between normalized displacement velocity and normalized pressure velocity using both total (r = 0.76, P less than 0.001) and developed (r = 0.75, P less than 0.001) displacement and pressure. Significant correlations with several other indexes of left ventricular function (end-diastolic pressure, peak dP/dt, maximal velocity of the contractile elements at zero load[Vmax]) were also observed. It is concluded that the index dD/dt/D of the left apex cardiogram is an important noninvasive tool for assessing left ventricular function in man.

Serum LP(a) levels in African aboriginal Pygmies and Bantus, compared with Caucasian and Asian population samples.

Serum lipoprotein(a) (Lp(a)) and its correlates were studied in African Aboriginal Pygmies (n = 146) and Bantus (n = 208) from Cameroon. Geometric mean Lp(a) levels were 274 and 289 mg/l in Bantu males and females, respectively, and 220 and 299 mg/l in Pygmy males and females, the gender difference being significant in Pygmies (p = 0.024). In Pygmies 41% and 52% of the males and females, respectively, had Lp(a) levels above 300 mg/l, compared with 47% and 55% in Bantus. Overall, Lp(a) levels did not significantly differ between Pygmies and Bantus, and did not correlate with age, body mass index (BMI), systolic and diastolic blood pressure. Compared with healthy Asian and Caucasian population samples, age- and BMI-adjusted geometric Lp(a) means were 2.3- to 5.0-fold higher in Pygmy and Bantu males, and 2.9- to 3.6-fold higher in Pygmy and Bantu females (p < or = 0.05). Across the population samples studied ethnicity predicted 12% and 17% of serum Lp(a) variance in males and females, respectively.

Intramyocardial pressure in the canine heart. An experimental study.

During 11 acute open-chest experiments with dogs, intramyocardial pressure was measured in the anterior wall of the left ventricle with a miniature pressure transducer mounted on a 1.6 mm diameter needle. Pressures were measured at the subendocardium (+/- 10 mm), midwall (+/- 7.5 mm), and subepicardium (+/- 5 mm). Simultaneous recordings of left ventricular pressure and two measures of intramyocardial pressure were made during control, acute volume overload, and after administration of verapamil. Maximal amplitude of the subendocardial pressure was higher and the maximal amplitude of the subepicardial pressure was lower than maximal left ventricular pressure for all interventions (p less than 0.001 and p less than 0.01). During volume overload left ventricular pressure increased more than intramyocardial pressure (left ventricular pressure 34%, subendocardial pressure 6%, midwall pressure 14%, and subepicardial pressure 14%). After the administration of verapamil intramyocardial pressure decreased more than left ventricular pressure (left ventricular pressure 16%, subendocardial pressure 26%, midwall pressure 13%, subepicardial pressure 32%). Positive and negative first derivatives of subendocardial pressure were higher than those of left ventricular pressure during control and after verapamil (between p less than 0.01 and p less than 0.001). Positive and negative first derivatives of subepicardial pressure were lower than those of left ventricular pressure during all interventions (p less than 0.001). The timing of the C-point (onset of mechanical contraction) and the positive first derivative of all tracings was synchronous within 8 msec in all interventions. The 0-point (crosspoint of the tangent to the diastolic plateau and the tangent to the relaxation slope; early diastole) of intramyocardial pressure came later than the 0-point of left ventricular pressure, indicating longer relaxation times in the myocardium (subendocardial pressure: control, p less than 0.001, volume, p less than 0.05, verapamil, no significance; midwall pressure: between p less than 0.05 and p less than 0.001; subepicardial pressure: between p less than 0.01 and p less than 0.001).

Coffee consumption and serum cholesterol: an epidemiological study in Belgium.

In a Belgian population group of 15,954 male and 2116 female soldiers and their spouses the relationship between coffee drinking and serum cholesterol has been studied. A moderate but highly significant monotonic positive relationship between coffee drinking and both serum total and non-high density lipoprotein (HDL)-cholesterol was observed in men (p less than 0.001) even when adjusted for the confounding effects of age, body mass index, smoking, alcohol, and dietary fat and cholesterol intake. Men drinking at least three cups of coffee daily had a mean level of serum total cholesterol about 4 mg/dl and of non-HDL-cholesterol about 3 mg/dl higher than those who did not drink coffee. No significant effect of coffee drinking on HDL-cholesterol was observed in men. In women coffee-drinking did not influence any of the measured serum lipids.

Fish consumption is inversely associated with male lung cancer mortality in countries with high levels of cigarette smoking or animal fat consumption.

BACKGROUND: A striking difference in fish consumption and lung cancer mortality (LCM) exists among populations worldwide. This study investigated the relation between fish consumption and LCM at the population level. METHODS: Sex-specific LCM data, mostly around 1993 and fish consumption data for 10 periods 1961-1994 in 36 countries were obtained from WHO and FAO, respectively. RESULTS: A significant inverse correlation exists between log fish consumption and LCM rate in 9 out of the 10 time periods (r = -0.34 to r = -0.46, P = 0.044 to P = 0.005). After adjusting for smoking and other confounders, log fish consumption (% of total energy [% E]) was inversely and significantly associated with LCM rate (per 100 000 per year) in all 10 time periods (beta = -26.3 to beta = -36.7; P = 0.0039 to P < 0.0001). The stratified analysis showed that this inverse relation was significant only in countries with above median level of smoking (>2437 cigarettes/adult/year) or animal fat minus fish fat consumption (22.4% E). An increase in fish consumption by 1% E was calculated to reduce mean male LCM rate of the populations examined in the age class of 45-74 years by 8.4%. In women, no significant relation between fish consumption and LCM could be established. CONCLUSIONS: Fish consumption is associated with a reduced risk from LCM, but this possible protective effect is clear-cut only in men and in countries with high levels of cigarette smoking or animal fat consumption.

The sex ratio of mortality and its secular trends.

BACKGROUND: The mortality level from all causes is different between populations and it has decreased for both men and women in most countries in the last decades. However, there is a difference in the male/female sex ratio of mortality between populations and its time trends and the reasons for these differences remain unclear. METHODS: The sex ratio of all-cause mortality and the main causes of death, i.e. total cardiovascular disease and cancer, for 30 populations in 1988 (mean of 1987-1989), and the time trends of the sex ratio for 27 populations are analysed. RESULTS: Large differences in the sex ratio of mortality exist among the studied populations. The sex ratio of all-cause, total cardiovascular and cancer mortality markedly increased in most countries during recent decades. CONCLUSIONS: The sex ratio of all-cause mortality and its time trends correlated significantly and positively with the sex ratio of mortality and its time trends from total cardiovascular disease and cancer. The differences of the sex ratio of mortality and their time trends between populations cannot be explained by genetic factors. They could be attributed to differences in life style. A different exposure and different reaction to the risk factors of cardiovascular diseases and cancer, e.g. saturated fat intake, alcohol intake and smoking habits, between men and women are considered to be the main causes for these differences in the sex ratio of mortality.