Biomedical subjects

A N Phillips

Publications and source records attributed to A N Phillips.

At least 199 records · Page 11Linked to original sources

PubMed1991

How independent are "independent" effects? Relative risk estimation when correlated exposures are measured imprecisely.

A relative risk estimate which relates an exposure to risk of disease will tend to be estimated too close to unity if that exposure is subject to random measurement error or intra-subject variability. "Independent" relative risk estimates, for the effect of one exposure after adjusting for confounding exposures, may be biased in either direction, depending on the amount of measurement imprecision in the exposure of interest and in the confounders. We describe two methods which estimate the bias in multivariate relative risk estimates due to the effect of measurement imprecision in one or more of the exposure variables in the model. Results from the two methods are compared in an example involving HDL cholesterol, triglycerides and coronary heart disease. In this example, the degree of bias in relative risk estimates is shown to be highly dependent on the amount of measurement imprecision ascribed to the exposures. It is concluded that when two exposures are substantially correlated, and one or both is subject to sizeable measurement imprecision, a study in which exposures are measured only once will be inadequate for investigating the independent effect of the exposures. Where feasible, epidemiologists should seek study populations where the correlation between the exposures is smaller.

Bias↗

PubMed1991

p24 antigenaemia, CD4 lymphocyte counts and the development of AIDS.

A cohort of 111 HIV-infected haemophiliacs has been followed for up to 11 years, during which time 33 patients have been diagnosed with AIDS. Twenty-seven of the cohort developed detectable p24 antigenaemia while remaining free of AIDS. These patients experienced an increased risk of progression to AIDS compared with those patients who were persistently p24-negative (relative risk 7.24; P less than 0.0001, Cox proportional hazards model). The relative risk was reduced to 5.42 (P less than 0.0001) after adjustment for age and cytomegalovirus seropositivity. After adjustment for the patients' declining CD4 lymphocyte count during follow-up, the relative risk fell dramatically to 1.97 and became non-significant (P = 0.2). p24-antigenaemic patients tended to develop AIDS at levels of similar CD4 lymphocyte counts to those who were persistently p24-antigen-negative (median CD4 lymphocyte counts, 70 and 50 x 10(6)/l, respectively). These results suggests that the association between p24 antigenaemia and the rate of progression to AIDS can be explained largely by a more rapid decline in CD4 lymphocyte count among patients with p24 antigenaemia than in those without. The major pathological effects of increased plasma viral load, as detected by the presence or absence of p24 antigenaemia, appear to act via progressive CD4 lymphocyte depletion.

Acquired Immunodeficiency Syndrome↗

PubMed1991

More rapid progression to AIDS in older HIV-infected people: the role of CD4+ T-cell counts.

The tendency for older people with HIV infection to progress more rapidly to AIDS than younger people was studied in a group of 111 anti-HIV-positive haemophiliacs followed for up to 10 years from seroconversion. After 7 years of seropositivity, those aged over 30 years at the time of the first positive anti-HIV test had a cumulative progression rate to AIDS of 50%, compared with only 12% for those aged 10-19 years (Kaplan-Meier estimates). Overall, the relative risk of developing AIDS by any given time after seroconversion was 1.45 for each 10 year increase in age (p = 0.002; 95% confidence limits of 1.15, 1.85; Cox proportional hazards model). After adjustment for the CD4+ T-cell count (median of 10 count measurements per patient, fitted as a time-dependent covariate), the relative risk fell to 1.31 but remained statistically significant (p less than 0.05; 95% confidence limits of 1.03, 1.67). This implies that older people may be at higher risk of progression than their younger counterparts, even if their CD4+ T-cell counts are the same. Hence, prophylaxis against opportunistic infections may be indicated at higher CD4+ T-cell counts in older people than in younger people.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Serum calcium and blood pressure.

The association between serum calcium and blood pressure was examined in a sample of 7,735 healthy middle-aged British men (The British Regional Heart Study). There was a small but significant correlation between serum calcium and both systolic and diastolic blood pressure (r = 0.15 and 0.11, respectively; P less than 0.0001) after adjusting for age. This association was diminished after adjustment for serum albumin, but remained significant (r = 0.10 and 0.07; P less than 0.0001). This finding is consistent with results from previous studies. To assess whether the association between serum calcium and blood pressure is independent of the levels of other blood constituents, 20 biochemical and haematological factors were examined to identify possible confounding factors. The association between calcium and blood pressure disappeared after adjustment for serum globulins and haematocrit in addition to age and serum albumin. Thus, these factors appear to mediate the weak association between serum calcium and both systolic and diastolic blood pressure. There does not appear to be an independent relationship between serum calcium and blood pressure.

Adult↗

PubMed1990

ABO blood group and ischaemic heart disease in British men.

OBJECTIVE: To establish whether ABO blood group is related to ischaemic heart disease on an individual and geographic basis in Britain. DESIGN: Prospective study of 7662 men with known ABO blood group selected from age-sex registers in general practices in 24 British towns. MEASUREMENTS: ABO blood group, standard cardiovascular risk factors, social class, and presence or absence of ischaemic heart disease determined at entry to study. END POINTS: Eight year follow up of fatal and nonfatal ischaemic heart disease events achieved for 99% of study population. RESULTS: Towns with a higher prevalence of blood group O had higher incidences of ischaemic heart disease. In individual subjects, however, the incidence of ischaemic heart disease was higher in those with group A than in those with other blood groups (relative risk 1.21, 95% confidence limits 1.01 to 1.46). Total serum cholesterol concentration was slightly higher in subjects of blood group A. No other cardiovascular risk factor (including social class) was related to blood group. CONCLUSIONS: Blood group A is related to the incidence of ischaemic heart disease in individual subjects. Geographic differences in the distribution of ABO blood groups do not explain geographic variation in rates of ischaemic heart disease in Britain. The findings do not support the view that ABO blood group and social class are related.

ABO Blood-Group System↗

PubMed1990

Prognostic scores for detecting a high risk group: estimating the sensitivity when applied to new data.

The sensitivity of a prognostic scoring system will tend to be exaggerated if the scoring system is both derived and validated on the same data. This paper provides, by analogy to regression with error in an explanatory variable, an intuitive basis for the methodological results of Copas which seek to estimate the degree of such exaggeration. There was good agreement between Copas' results and those achieved in a series of cross-validation exercises where logistic regression models predicting the risk of ischaemic heart disease were derived using data from the prospective British Regional Heart Study. When truly important variables were included, the exaggeration of the sensitivity increased as the number of cases of disease available decreased. It is concluded that Copas' method, which is easy to implement in practice, may be helpful in realistically anticipating the extent of such exaggeration, and that it can be usefully employed before pursuing a scoring system on newly collected data.

Adult↗

PubMed1989

Concentrations of high density lipoprotein cholesterol, triglycerides, and total cholesterol in ischaemic heart disease.

OBJECTIVE: To assess the roles of serum concentrations of total cholesterol, high density lipoprotein cholesterol, and triglycerides in predicting major ischaemic heart disease. DESIGN: Men recruited for the British regional heart study followed up for a mean of 7.5 years. SETTING: General practices in 24 British towns. PATIENTS: 7735 Middle aged men. END POINT: Predictive value of serum concentrations of lipids. MEASUREMENTS AND MAIN RESULTS: At initial screening serum concentrations of total cholesterol, high density lipoprotein cholesterol, and triglycerides were determined from non-fasting blood samples. Altogether 443 major ischaemic heart disease events (fatal and non-fatal) occurred during the study. Men in the highest fifth of the distribution of total cholesterol concentration (greater than or equal to 7.2 mmol/l) had 3.5 times the risk of ischaemic heart disease than did men in the lowest fifth (less than 5.5 mmol/l) after adjustment for high density lipoprotein cholesterol concentration and other risk factors. Men in the lowest fifth of high density lipoprotein cholesterol concentration (less than 0.93 mmol/l) had 2.0 times the risk of men in the highest fifth (greater than or equal to 1.33 mmol/l) after adjustment for total cholesterol concentration and other risk factors. Men in the highest fifth of triglyceride concentration (greater than or equal to 2.8 mmol/l) had only 1.3 times the risk of those in the lowest fifth (less than 1.08 mmol/l) after adjustment for total cholesterol concentration and other risk factors; additional adjustment for high density lipoprotein cholesterol concentration made the association with ischaemic heart disease disappear. CONCLUSIONS: Serum concentration of total cholesterol is the most important single blood lipid risk factor for ischaemic heart disease in men. High density lipoprotein cholesterol concentration is less important, and triglyceride concentrations do not have predictive importance once other risk factors have been taken into account.

Adult↗

PubMed1989

Migration and geographic variations in ischaemic heart disease in Great Britain.

The British Regional Heart Study seeks to explain the geographic variations in cardiovascular disease in Great Britain. A strong geographic gradient in the risk of a major ischaemic heart disease (IHD) event was found in 7735 middle-aged men who were followed up for 6.5 years. Regardless of where they were born, men examined in Scotland experienced the highest IHD risk, while those examined in the South of England had the lowest. The place of examination (ie, residence) was a more important determinant of the risk of a major IHD event than the place of birth. It seems unlikely that the geographic differences in IHD risk among middle-aged British men can be directly explained by their genetic inheritance or by their prenatal and postnatal diet.

Adult↗

PubMed1989

Sample size requirements for prospective studies, with examples for coronary heart disease.

Methods of determining the required number of disease cases for estimation of relative odds in prospective studies are evaluated, with examples from coronary heart disease. Data from a British prospective study of coronary heart disease are used in simulation exercises to assess the reliability of estimation formulae for both continuous and categorical risk factors. For continuous risk factors, a univariate formula based on estimation of the standardized relative odds (Whittemore A. S. JAMA 1981; 76: 27-32 [1]), gives reliable estimation of the required number of disease cases, provided the risk factor has a near normal distribution. An extension of the formula to adjustment for other risk factors, was less satisfactory, perhaps because of departures from multivariate normality. For categorical risk factors, an adaption of a univariate method for case control studies (Smith PG, Day NE. Int J Epidemiol 1984; 13: 356-365 [2]), gives reliable estimates of the number of cases required. However, this depends on approximate prior knowledge of the relative odds. In general, prospective studies of coronary heart disease risk factors should aim for at least 400 cases to enable sufficient accuracy of estimation.

Adult↗

PubMed1989

Short stature, lung function and risk of a heart attack.

In a large prospective study of cardiovascular disease in 7735 middle-aged men--the British Regional Heart Study--the 443 subjects who experienced a major ischaemic heart disease event within 7.5 years of follow-up were on average 1.6 cm shorter than the other men (p less than 0.001). The risk of heart attack was approximately twice as great in the shortest quintile of men compared with the tallest quintile. When a number of recognized risk factors for ischaemic heart disease were taken into account--age, social class, serum total cholesterol, HDL-cholesterol, systolic blood pressure, cigarette smoking--there was a marked reduction in the risk of heart attack associated with height. When a measure of lung function (FEV1 not standardized for height) was adjusted for in addition to these risk factors, the height-related risk of heart attack disappeared. Indeed, FEV1 alone was sufficient to account for most of the association between height and the risk of heart attack.

Adult↗

PubMed1988

Prediction of men at high risk of heart attack and its relevance to pilots.

In this paper we have extrapolated from data on the general population of middle-aged men and made suggestions for risk prediction and prevention policy in aircrew. As suggested previously, it would be helpful in future if data on the risk of heart attack in pilots could be generated from a central recording system covering both current pilots and those who retire for whatever reason. Indefinite follow-up information on ischaemic events would also be particularly helpful.

Adult↗

PubMed1988

Parental death from heart disease and the risk of heart attack.

In the British Regional Heart Study, 7735 men aged 40-59 years were asked at initial screening whether their father or mother was alive or dead and to what cause any death had been attributed. They were followed up for the occurrence of major ischaemic heart disease events. At screening the men reported that 23% of the fathers and 43% of the mothers were alive and that 19% of the fathers and 11% of the mothers had died of heart trouble. In a sample of parental deaths, the death certificate was obtained and it was found that a son's report of a parental death from 'heart trouble' was a reliable indication that death had been certified to ischaemic heart disease. However, about half of the parental deaths certified as ischaemic heart disease were not reported as 'heart trouble' by their sons. A major ischaemic heart disease event was experienced by 336 men over an average follow-up of 6.2 years. Men who said their father had died from 'heart trouble' were at twice the risk of a major ischaemic heart disease event compared with men whose fathers were still alive and 1.5 times the risk of men who reported their father to be dead from another or unknown cause, even after accounting for age, systolic blood pressure, serum total cholesterol, cigarette smoking and serum HDL-cholesterol. For men with mother dead from heart trouble, the corresponding figures were 1.3 and 1.0.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

The role of risk factors in heart attacks occurring in men with pre-existing ischaemic heart disease.

The importance of three risk factors--serum total cholesterol, systolic blood pressure, and cigarette smoking--on the risk of new major ischaemic heart disease events in men who already have evidence of ischaemic heart disease was assessed. Data from the initial examination in a large prospective study of cardiovascular disease in middle aged men (the British Regional Heart Study) were used to separate 7710 men into three groups on the basis of a resting electrocardiogram, a standardised chest pain questionnaire, and recall of a doctor's diagnosis of angina or of a previous heart attack: (group 1) no evidence of ischaemic heart disease (75%), (group 2) evidence of ischaemic heart disease short of a definite myocardial infarction (20%), (group 3) definite myocardial infarction (6%). In the average follow up period of 7.5 years, 443 men suffered a new major event caused by ischaemic heart disease (fatal or non-fatal myocardial infarction or sudden cardiac death). Age standardised event rates were determined for each of the three groups for varying levels of the established risk factors. Cigarette smoking is strongly associated with the event rate in group 1 but in men with existing heart disease, especially group 3, differences in risk between the smoking categories were smaller. The strong relation between systolic blood pressure and event rate persisted in groups 1 and 2 but not in group 3. The positive association between serum concentration of total cholesterol and the event rate was strongest in group 1 and weaker in groups 2 and 3, though it remained highly significant. These observations, taken together with the results of previous prospective studies and intervention trials, suggest that the important association between serum total cholesterol and the risk of heart attack persists in men with pre-existing ischaemic heart disease, including myocardial infarction. Therefore, in these men the reduction of serum total cholesterol concentration may be at least as important as it is in men without evidence of ischaemic heart disease.

Adult↗

PubMed1987

Social class differences in ischaemic heart disease in British men.

To examine why ischaemic heart disease (IHD) mortality rates in Britain are higher in manual than in non-manual workers 7735 middle-aged men in the British Regional Heart Study were followed up for 6 years, during which time 336 men experienced a major IHD event (fatal or non-fatal myocardial infarction or sudden cardiac death). The prevalence rates of IHD at screening, were higher in manual workers. Also, the attack rate of major IHD events during follow-up was 44% higher in manual workers. Marked differences in cigarette smoking contributed substantially to the increased risk of IHD in manual workers, who also had higher levels of blood pressure, were more obese, and took much less physical activity in leisure time. Adjustment for differences in these risk factors narrowed the gap between manual and non-manual workers in attack rates of IHD. Since the risk of IHD in Great Britain is high in all social classes, there would seem to be little justification for any overall policy for prevention of IHD to focus on social class. However, anti-smoking strategies might well take into account the social class differences described.

Adult↗

PubMed1987

Alcohol and ischaemic heart disease in middle aged British men.

The relation between alcohol intake and ischaemic heart disease was examined in a large scale prospective study of middle aged men drawn from general practices in 24 British towns. After an average follow up of 6.2 years 335 of the 7729 men had experienced a myocardial infarction (fatal or non-fatal) or sudden cardiac death. No significant relation was found between reported alcohol intake and the incidence of such events. Though the group of light daily drinkers had the lowest incidence of ischaemic heart disease events, it also contained the lowest proportion of current smokers, had the lowest mean blood pressure, had the lowest mean body mass index, and contained the lowest proportion of manual workers. These characteristics are more likely to account for the apparent protective effect of alcohol against ischaemic heart disease than a direct effect of alcohol. Compared with the effects of established risk factors alcohol seems to be quite unimportant in the development of ischaemic heart disease.

Adult↗

PubMed1987

A scoring system to identify men at high risk of a heart attack.

A scoring system for identification of men at high risk of a heart attack within 5 years of screening is presented. The full scoring system includes an electrocardiogram and blood cholesterol measurement and the top fifth of the distribution of this full score yields 59% of the major ischaemic heart disease events occurring in the 5 years after screening. An intermediate scoring system, without an electrocardiogram but retaining blood cholesterol, yields 58% of cases from the top fifth of the score distribution. A basic (GP) score, without electrocardiogram or blood cholesterol measurement, yields 54% of cases and is recommended for use in opportunistic screening in general practice. This high risk strategy would increase public awareness of the size of the problem, help to prevent premature death and provide a useful complement to the population strategies of health education and government policy.

Adult↗

PubMed1986

Identifying men at high risk of heart attacks: strategy for use in general practice.

A strategy was devised for identifying men at high risk of acute myocardial infarction or sudden ischaemic death. A risk score was devised using cigarette smoking, mean blood pressure, recall of ischaemic heart disease or diabetes mellitus diagnosed by a doctor, history of parental death from "heart trouble," and the presence of angina reported on a questionnaire. The top fifth of the score distribution identified 53% of ischaemic heart disease cases--that is, men who subsequently experienced major ischaemic heart disease over the next five years. The addition of serum total cholesterol concentration and electrocardiographic evidence only slightly improved prediction (to 59%) and would have considerably increased the cost and effort of screening. Using this risk score on an opportunistic basis could be particularly valuable in general practice. Management of this high risk group is regarded as appropriate medical care and is complementary to the population approach to preventing ischaemic heart disease. Such a strategy for reducing the incidence of and mortality from ischaemic heart disease in men at high risk would also increase professional and public awareness of the need for preventive action.

Adult↗

PubMed1986

High density lipoprotein cholesterol is not a major risk factor for ischaemic heart disease in British men.

The concentration of high density lipoprotein cholesterol (HDL cholesterol) in serum was measured at initial examination in a large prospective study of men aged 40-59 drawn from general practices in 24 British towns. After an average follow up of 4.2 years 193 cases of major ischaemic heart disease had been registered in 7415 men in whom both HDL cholesterol and total cholesterol values had been measured. The mean HDL cholesterol concentration was lower in the men with ischaemic heart disease ("cases") compared with other men, but the difference became small and non-significant after adjustment for age, body mass index, blood pressure, cigarette smoking, and concentration of non-HDL cholesterol. The higher mean concentration of non-HDL cholesterol in "cases" remained highly significant after adjustment for other factors. Men in the highest fifth of non-HDL cholesterol values had over three times the risk of major ischaemic heart disease compared with men in the lowest fifth. Multivariate analysis showed that non-HDL cholesterol was a more powerful predictor of risk than the HDL to total cholesterol ratio. These British findings were compared with six other prospective studies. All the larger studies showed similar results, suggesting that HDL cholesterol is not a major risk factor in the aetiology of ischaemic heart disease.

Adult↗