Martin Shipley

INEQUALITIES IN DEATH - SPECIFIC EXPLANATIONS OF A GENERAL PATTERN

In the Whitehall study, 17 530 civil servants were classified according to employment grade, and their mortality was recorded over 10 years. There was a steep inverse relation between grade and mortality. Compared with the highest grade (administrators), men in the lowest grade had 3 times the mortality rate from coronary heart disease, from a range of other causes, and from all causes combined. This is larger than the mortality differences, nationally, between classes I and V. Smoking and other coronary risk factors are more common in the lowest grades, but these differences account for only part of the mortality difference. The similarity of the risk gradient from a range of specific diseases could indicate the operation of factors affecting general susceptibility. The inverse relation between height and mortality suggests that factors operating from early life may influence adult death rates.

Risk of stroke in non-rheumatic atrial fibrillation.

Estimates of the risk of stroke for men with non-rheumatic atrial fibrillation were obtained from two large cohort studies--the Whitehall Study of London Civil Servants and the British Regional Heart Study. The first cohort provided an estimated relative risk of stroke of 6.9 compared with controls. This increased risk confirms that of the other prospective estimate, 5.6, found in the Framingham study. In the second cohort only one of the men at risk had a stroke, and the risk estimate did not differ significantly from unity. The absolute rates of stroke in both cohorts were lower than those reported in the Framingham study, implying a lesser potential benefit from preventive measures. These lower rates should be considered in the planning of trials. The risk of stroke was significantly associated with raised systolic or diastolic blood pressure but not with age or coronary heart disease.

ALCOHOL AND MORTALITY: A U-SHAPED CURVE

In a longitudinal study of civil servants, 1422 men were classified according to their average daily alcohol intake. Over 10 years of follow-up, the mortality rate was lower in men reporting moderate alcohol intake than in either non-drinkers or heavier drinkers (greater than 34 g alcohol per day). Cardiovascular mortality was greater in non-drinkers and non-cardiovascular mortality was greater in the heavier drinkers. The heavier drinkers had higher mean blood pressures and contained a greater proportion of smokers. A multivariate analysis showed this U-shaped relationship between reported alcohol consumption and subsequent mortality to be largely independent of differences in smoking, blood pressure, plasma cholesterol, and grade of employment.

Intermittent claudication, heart disease risk factors, and mortality. The Whitehall Study.

In the Whitehall study, 18,388 subjects aged 40-64 years completed a questionnaire on intermittent claudication. Of these subjects, 0.8% (147) and 1% (175) were deemed to have probable intermittent claudication and possible intermittent claudication, respectively. Within the 17-year follow-up period, 38% and 40% of the probable and possible cases, respectively, died. Compared with subjects without claudication, the probable cases suffered increased mortality rates due to coronary heart disease and cerebrovascular disease, but the mortality rate due to noncardiovascular causes was not increased. Possible cases demonstrated increased mortality rates due to cardiovascular and noncardiovascular causes. This difference in mortality pattern may be due to chance. Possible and probable cases still showed increased cardiovascular and all-cause mortality rates after adjusting for coronary risk factors (cardiac ischemia at baseline, systolic blood pressure, plasma cholesterol concentration, smoking behavior, employment grade, and degree of glucose intolerance). Intermittent claudication is independently related to increased mortality rates. It is not a rare condition, and simple questionnaires exist for its detection. The latter can be usefully incorporated in cardiovascular risk assessment and screening programs.

PLASMA LIPIDS AND MORTALITY: A SOURCE OF ERROR

Cause-specific mortality-rates were calculated in 17 718 men aged 40-64 years who participated in the Whitehall Study. Over a 7 1/2 year follow-up, total mortality showed a J-shaped relation to the plasma cholesterol concentration measured at entry to study. This shape resulted from a strong positive relation of plasma cholesterol with deaths from coronary heart-disease (CHD) combined with an opposite (inverse) relation between plasma cholesterol and deaths from other causes. Cancer mortality was 66% higher in the group with the lowest plasma cholesterol than in the group with the highest plasma cholesterol. Further analysis showed that this inverse association between plasma cholesterol and non-CHD deaths was confined to the first 2 years of follow-up; beyond this time total mortality and cholesterol level were evenly and positively correlated. Analysis of data from the Framingham study revealed the same phenomenon, which is presumed to result from the metabolic consequences of cancer which was present but unsuspected at the time of examination.

Does Autonomic Function Link Social Position to Coronary Risk? The Whitehall II Study

Background—Laboratory and clinical studies suggest that the autonomic nervous system responds to chronic behavioral and psychosocial stressors with adverse metabolic consequences and that this may explain the relation between low social position and high coronary risk. We sought to test this hypothesis in a healthy occupational cohort. Methods and Results—This study comprised 2197 male civil servants 45 to 68 years of age in the Whitehall II study who were undergoing standardized assessments of social position (employment grade) and the psychosocial, behavioral, and metabolic risk factors for coronary disease previously found to be associated with low social position. Five-minute recordings of heart rate variability (HRV) were used to assess cardiac parasympathetic function (SD of N-N intervals and high-frequency power [0.15 to 0.40 Hz]) and the influence of sympathetic and parasympathetic function (low-frequency power [0.04 to 0.15 Hz]). Low employment grade was associated with low HRV (age-adjusted trend for each modality, P≤0.02). Adverse behavioral factors (smoking, exercise, alcohol, and diet) and psychosocial factors (job control) showed age-adjusted associations with low HRV (P<0.03). The age-adjusted mean low-frequency power was 319 ms2 among those participants in the bottom tertile of job control compared with 379 ms2 in the other participants (P=0.004). HRV showed strong (P<0.001) linear associations with components of the metabolic syndrome (waist circumference, systolic blood pressure, HDL cholesterol, triglycerides, and fasting and 2-hour postload glucose). The social gradient in prevalence of metabolic syndrome was explained statistically by adjustment for low-frequency power, behavioral factors, and job control. Conclusions—Chronically impaired autonomic function may link social position to different components of coronary risk in the general population.

Body mass index and associations of sodium and potassium with blood pressure in INTERSALT.

This report further examines the relation of body mass index (BMI) to associations of 24-hour urinary sodium, potassium, and sodium-potassium ratio with blood pressure in INTERSALT, a 52-center international study of electrolytes and blood pressure. Analyses without adjustment for BMI indicated average systolic pressure greater by 6.00 mm Hg per 100 mmol higher sodium and diastolic by 2.52 mm Hg. With adjustment for BMI, these values were reduced to 3.14 and 0.14 mm Hg, respectively. For the sodium-potassium ratio, blood pressure associations were stronger when not adjusted for BMI, and for potassium, adjustment generally had little effect. To explore possible interactions of these variables with BMI in relation to blood pressure, the 52 centers were divided into two groups of 26 based on whether the center median for BMI was less than or greater than or equal to 24.5 kg/m2, and individuals within each of the 52 centers were classified into lower- or higher-BMI groups based on individual BMI less than or greater than or equal to 24.1 kg/m2. Sodium and the sodium-potassium ratio were positively and significantly and potassium inversely and significantly related to systolic pressure in all four of these subgroups, and the sodium-potassium ratio and potassium were related to diastolic pressure in two and three subgroups, respectively. Electrolyte-blood pressure associations did not differ significantly between the two subgroups of centers or between the two subgroups based on individuals.(ABSTRACT TRUNCATED AT 250 WORDS)

Higher blood pressure in adults with less education. Some explanations from INTERSALT.

An inverse association between social class and disease has frequently been reported; education, an indicator of social class, was negatively related to blood pressure in several studies. Reasons are not clear. INTERSALT, an international study on electrolytes and blood pressure, obtained data on years of education for 10,079 adults in 52 centers in 32 countries. Data presented here are for 47 centers, omitting five where the population in the sample had no education or no differences in educational level. Regression coefficients were calculated for the education-blood pressure association in each center. An inverse association was found for men in 28 centers and for women in 38. Center coefficients were combined to give a studywide estimate of that association. When adjusted only for age, systolic pressure in men was 1.3 mm Hg higher for 10 fewer years of education (p less than 0.05) and for women 4.5 mm Hg higher (p less than 0.001). However, when adjusted also for five lifestyle factors (24-hour sodium and potassium excretion, body mass index, alcohol intake, and smoking), these estimates were reduced by about one half, and the inverse association was no longer significant for men. Similar findings were obtained for diastolic pressure. Those with less education had on average higher sodium excretion, lower potassium excretion, greater body mass, and higher alcohol intake, all factors tending to increase blood pressure. Improvement of these factors, which help explain the differences in blood pressure related to years of education, has the potential to reduce the blood pressure disadvantage associated with lower socioeconomic status.

Hyperglycaemia and coronary heart disease: the Whitehall study.

Abstract In a 5-yr follow-up of 18,403 male London civil servants, aged 40–64 yr, coronary heart disease mortality has been examined in relation to baseline levels of blood glucose concentration measured 2 hr after a 50 g oral glucose load. When deciles of the blood sugar distribution were considered, no trend of age-adjusted 5-yr CHD mortality rates was apparent. There was also no significant trend in the prevalence of Minnesota-Coded ECG abnormalities with deciles of blood sugar. However, for individuals with blood sugars above the 98th centile (106 mg/dl for ages 40–59 yr; 110 mg/dl for ages 40–64 yr) there was approximately a doubling of CHD mortality, this increase being independent of age and blood pressure. The prevalence of ECG abnormalities (Whitehall Criteria) was also increased above the 90th centile of blood sugar.

Confounding of occupation and smoking: Its magnitude and consequences

In a recent contribution to this journal, Sterling and Weinkam discuss the importance of the confounding of occupation and smoking when considering the contribution of smoking to mortality risk. In this report we provide estimates of the potential magnitude of this effect using data from a cohort study. It is shown that failing to consider possible confounding by socio-economic factors can lead to over-estimating of the strength of the relationship between smoking and mortality. The implications of these findings for the interpretation of results derived from observational studies are discussed.