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PubMed2006

Does IQ explain socioeconomic inequalities in health? Evidence from a population based cohort study in the west of Scotland.

OBJECTIVE: To test the hypothesis that IQ is a fundamental cause of socioeconomic inequalities in health. DESIGN: Cross sectional and prospective cohort study, in which indicators of IQ were assessed by written test and socioeconomic position by self report. SETTING: West of Scotland. PARTICIPANTS: 1347 people (739 women) aged 56 in 1987. MAIN OUTCOME MEASURES: Total mortality and coronary heart disease mortality (ascertained between 1987 and 2004); respiratory function, self reported minor psychiatric morbidity, long term illness, and self perceived health (all assessed in 1988). RESULTS: In sex adjusted analyses, indices of socioeconomic position (childhood and current social class, education, income, and area deprivation) were significantly associated with each health outcome. Thus the greatest risk of ill health and mortality was evident in the most socioeconomically disadvantaged groups, as expected. After adjustment for IQ, a marked attenuation in risk occurred for poor mental health (range of attenuation in risk ratio across the five socioeconomic indicators: 15-58%), long term illness (25-53%), poor self perceived health (41-56%), respiratory function (44-66%), coronary heart disease mortality (31-111%), and total mortality (45-131%). Despite the clear reduction in the magnitude of these effects after controlling for IQ, in half of the associations examined the risk of ill health in socioeconomically disadvantaged people was still at least twice that of advantaged people. Statistical significance was lost for only 5/25 separate socioeconomic health gradients that showed significant relations in sex adjusted analyses. CONCLUSIONS: Scores from the IQ test used here did not completely explain the socioeconomic gradients in health. However, controlling for IQ did lead to a marked reduction in the magnitude of these gradients. Further exploration of the currently scant information about IQ, socioeconomic position, and health is needed.

Coronary Disease↗

PubMed1994

Insulin in ischaemic heart disease: are associations explained by triglyceride concentrations? The Caerphilly prospective study.

OBJECTIVE: To investigate the predictive value of fasting insulin concentrations for subsequent fatal or non-fatal ischaemic heart disease at five year follow up and to examine the associations between insulin and other indicators of risk. DESIGN: A prospective population study among 2512 men aged 45 to 59 at recruitment. SETTING: A whole population sample of men resident in Caerphilly, South Wales. MEASUREMENTS: At recruitment fasting blood samples were taken for measurement of plasma lipids and serum insulin. Men were re-examined at a five year follow up and ischaemic heart disease events during this period were assessed from hospital notes, death certificates, and electrocardiograms. MAIN RESULTS: Diabetic men and those men with a fasting blood glucose of > or = 8 mmol/l were excluded from all analyses. In a univariate analysis the incidence of ischaemic heart disease increased with increasing concentration of fasting insulin, such that for men in the top 20% of the insulin distribution the odds of developing ischaemic heart disease were 1.87 relative to men in the bottom 20%. On multivariate analysis this relation disappeared on adjusting for plasma triglycerides, body mass index, and evidence of ischaemic heart disease at recruitment. CONCLUSION: In this population in South Wales there was no evidence that the fasting insulin concentration is an independent risk factor for ischaemic heart disease. The univariate association between insulin and incident disease was almost entirely explained by the association of both with triglycerides and body mass index.

Follow-Up Studies↗

PubMed2005

Geographical variation in life expectancy at birth in England and Wales is largely explained by deprivation.

STUDY OBJECTIVE: To describe the population mortality profile of England and Wales by deprivation and in each government office region (GOR) during 1998, and to quantify the influence of geography and deprivation in determining life expectancy. DESIGN: Construction of life tables describing age specific mortality rates and life expectancy at birth from death registrations and estimated population counts. Life tables were created for (a) quintiles of income deprivation based on the income domain score of the index of multiple deprivation 2000, (b) each GOR and Wales, and (c) every combination of deprivation and geography. SETTING: England and Wales.PATIENTS/ PARTICIPANTS: Residents of England and Wales, 1998. MAIN RESULTS: Life expectancy at birth varies with deprivation quintile and is highest in the most affluent groups. The differences are mainly attributable to differences in mortality rates under 75 years of age. Regional life expectancies display a clear north-south gradient. Linear regression analysis shows that deprivation explains most of the geographical variation in life expectancy. CONCLUSIONS: Geographical patterns of life expectancy identified within these data for England and Wales in 1998 are mainly attributable to variations in deprivation status as defined by the IMD 2000 income domain score.

Adolescent↗

PubMed2004

Can cardiovascular risk factors and lifestyle explain the educational inequalities in mortality from ischaemic heart disease and from other heart diseases? 26 year follow up of 50,000 Norwegian men and women.

OBJECTIVE: Investigate the degree to which smoking, physical activity, marital status, BMI, blood pressure, and cholesterol explain the association between educational level and ischaemic heart disease (IHD) mortality and other forms of cardiovascular mortality, with main focus on IHD mortality. DESIGN: Prospective health examination survey study conducted in the period 1974-78. SETTING: Oppland, Sogn og Fjordane, and Finnmark counties in Norway. PARTICIPANTS: The sample comprised 22,712 men and 21,972 women, aged 35-49 at screening. The subjects were followed up with respect to mortality throughout year 2000. MAIN RESULTS: 4342 men and 2164 women died during the follow up, 1343 men and 258 women of IHD. IHD mortality risk was higher for people with low education compared with people with high education, and people with low education had more adverse risk factors. After adjustment for smoking the IHD mortality relative risk (RR) with 95% confidence limits, in the low educational group decreased from 1.33 (1.18 to 1.50) to 1.16 (1.03 to 1.31) for men, and from 1.72 (1.23 to 2.41) to 1.58 (1.13 to 2.22) for women. Further adjustment for physical activity, marital status, BMI, blood pressure, and cholesterol reduced the RR to 1.03 (0.91 to 1.17) for men and 1.24 (0.88 to 1.75) for women. CONCLUSIONS: Unfavourable cardiovascular risk factors and high IHD mortality are more prevalent among less educated than their highly educated peers. After simultaneous adjustment for all recorded risk factors, the excess IHD mortality in the low educational groups was reduced by 91% for men and 67% for women.

Adult↗

PubMed2006

The psychosocial versus material hypothesis to explain observed inequality in disability among older adults: data from the West of Scotland Twenty-07 Study.

OBJECTIVES: The possible mechanisms for explaining health inequality are subject to debate. This study considers the roles of psychosocial and material mechanisms in observed inequalities in disability among older people. DESIGN: Cross-sectional analysis of cohort study. PARTICIPANTS: 723 respondents aged 63 years from the West of Scotland Twenty-07 Study. MAIN OUTCOME MEASURE: The Office of Population Census and Surveys Multidimensional Disability Severity Score. Respondents were dichotomised to the highest scoring tertile, and compared with the lowest and mid-tertiles combined. EXPLANATORY MEASURES: Socioeconomic position across adulthood was measured in three ways. Respondents reported perceptions of their own financial position (perceived financial hardship) across four decades of adult life. Data on possession of several indicators of material wealth (eg, ownership of television and washing machine; material conditions) during the same periods were also ascertained. Standard occupational classification was also recorded, based on longest held occupation. The relationship between the measures of socioeconomic position and disability was examined using logistic regression, adjusting for sex, morbidity and lifestyle factors. RESULTS: Perceived financial hardship and material conditions in earlier decades of life were found to be associated with reported disability. However, in the fully adjusted model, there was stronger evidence for material conditions as a predictor of disability: across four decades they remained an independent risk factor for disability after adjustment for sex, morbidity, lifestyle factors and perceived financial hardship. Those in the most deprived material conditions group had 2 1/2 times the odds of reporting severe disability than those in the reference group. After adjustment, evidence for an association between perceived financial hardship and reported disability was not convincing. CONCLUSION: The data provide evidence to support the "material" explanation for observed inequalities in reported disability among older people.

Comorbidity↗

PubMed1988

Are malignant melanoma time trends explained by changes in histopathological criteria for classifying pigmented skin lesions?

The incidence of malignant melanoma in developed countries has been rising rapidly in recent years. Its causes and the reasons for this trend are uncertain. Changes in histopathological criteria for classifying pigmented skin lesions could explain the rising incidence rates. With support from the International Agency for Research on Cancer, this hypothesis is explored but not substantiated for time trends in the South Western Region, United Kingdom.

England↗

PubMed2003

Evolution of Wheat streak mosaic virus: dynamics of population growth within plants may explain limited variation.

Like many other plant RNA viruses, Wheat streak mosaic virus (WSMV) sequence diversity within and among infected plants is low given the large number of virions produced. This may be explained by considering aspects of plant virus life history. Intracellular replication of RNA viruses is predominately linear, not exponential, which means that the rate at which mutations accumulate also is linear. Bottlenecks during systemic movement further limit diversity. Analysis of mixed infections with two WSMV isolates suggests that about four viral genomes participate in systemic invasion of each tiller. Low effective population size increases the role of stochastic processes on dynamics of plant virus population genetics and evolution. Despite low pair-wise diversity among isolates, the number of polymorphic sites within the U.S. population is about the same as between divergent strains or a sister species. Characteristics of polymorphism in the WSMV coat protein gene suggest that most variation appears neutral.

Biological Evolution↗

PubMed1980

Wedged pressure recording and injection of contrast medium into the hepatic veins: a study performed on the livers of cadavers to explain clinical findings.

Portal and hepatic veins were injected with Microfil in the normal and cirrhotic livers of cadavers. Based on pathologic and anatomic studies previously reported and on the present investigation, the authors explain the background of wedged hepatic pressure recording and the findings when contrast medium is injected into a catheter wedged in a hepatic vein.

Catheterization↗

PubMed1993

High Km of GLUT-2 glucose transporter does not explain its role in insulin secretion.

Evidence indicates that the high-Km GLUT-2 function of the islet cells is essential for insulin secretion in response to glucose. To examine possible significance of the high-Km transport function of GLUT-2 in this secretory response, we have studied by computer simulation the effects of high- and low-Km glucose uptake on the steady-state intracellular glucose concentration and glucose phosphorylation in beta-cells. Our computations reveal that both the intracellular glucose concentration and the glucose phosphorylation catalyzed by glucokinase increase significantly as the extracellular glucose concentration increases from 5 to 20 mM, even with a transport Km as low as 1.5 mM, the lowest value known for GLUT-1. Our results indicate that the apparent requirement of GLUT-2 for glucose-sensitive insulin secretion cannot be explained simply by its high-Km transport function alone and suggest that an isoform-specific, direct coupling of GLUT-2 with a certain glycolytic enzyme, such as glucokinase, is essential for the secretory response.

Animals↗

PubMed2002

Load dependence of ventricular performance explained by model of calcium-myofilament interactions.

Although a simple concept of load-independent behavior of the intact heart evolved from early studies of isolated, intact blood-perfused hearts, more recent studies showed that, as in isolated muscle, the mode of contraction (isovolumic vs. ejection) impacts on end-systolic elastance. The purpose of the present study was to test whether a four-state model of myofilament interactions with length-dependent rate constants could explain the complex contractile behavior of the intact, ejecting heart. Studies were performed in isolated, blood-perfused canine hearts with intracellular calcium transients measured by macroinjected aequorin. Measured calcium transients were used as the driving function for the model, and length-dependent rate constants yielding the highest concordance between measured and model-predicted midwall stress at different isovolumic volumes were determined. These length-dependent rate constants successfully predicted contractile behavior on ejecting contractions. This, along with additional model analysis, suggests that length-dependent changes in calcium binding affinity may not be an important factor contributing to load-dependent contractile performance in the intact heart under physiological conditions.

Actin Cytoskeleton↗

PubMed2004

Virtual electrode theory explains pacing threshold increase caused by cardiac tissue damage.

The virtual electrode polarization (VEP) effect is believed to play a key role in electrical stimulation of heart muscle. However, under certain conditions, including clinically, its existence and importance remain unknown. We investigated the influence of acute tissue damage produced by continuous pacing with strong current (40-mA, 4-ms biphasic pulses with 4-Hz frequency for 5 min) on stimulus-generated VEPs and pacing thresholds. A fluorescent optical mapping technique was used to obtain stimulus-induced transmembrane potential distribution around a pacing electrode applied to the ventricular surface of a Langendorff-perfused rabbit heart (n = 5). Maps and pacing thresholds were recorded before and after tissue damage. Spatial extents of electroporation and cell uncoupling were assessed by propidium iodide (n = 2) and connexin43 (n = 3) antibody staining, respectively. On the basis of these data, passive and active three-dimensional bidomain models were built to determine VEP patterns and thresholds for different-sized areas of the damaged region. Electrophysiological results showed that acute tissue damage led to disappearance of the VEP with an associated significant increase in pacing thresholds. Damage was expressed in electroporation and cell uncoupling within an approximately 1.0-mm-diameter area around the tip of the electrode. According to computer simulations, cell uncoupling, rather than electroporation, might be the direct cause of VEP elimination and threshold increase, which was nonlinearly dependent on the size of the damaged region. Fiber rotation with depth did not substantially affect the numerical results. The study explains failure to stimulate damaged tissue within the concepts of the VEP theory.

Acute Disease↗

PubMed1989

Varying elastance concept may explain coronary systolic flow impediment.

We measured phasic arterial coronary inflow in the blood-perfused isolated cat heart (n = 5) with a balloon in the left ventricle under well-defined conditions, i.e., constant perfusion pressure, constant vasomotor tone (maximal vasodilation), and heart rate. The normalized amplitude (A) between systolic flow (Fs) and diastolic flow (Fd) [A = (Fd - Fs)/Fd] was related to systolic left ventricular pressure (Ps, range 1.6-17 kPa, 1 kPa = 7.5 mmHg) for different isovolumic beats obtained by changes in balloon volume and for low load isobarically ejecting beats (pressure 0.2 kPa). The data were fitted to A = a + bPs with a = 0.70 +/- 0.15 (SD) and b = 0.005 +/- 0.005 kPa-1. This relation indicates a very weak effect of left ventricular systolic pressure on normalized flow amplitude. Thus the hypothesis that left ventricular pressure is the sole determinant impeding coronary flow could not be confirmed. However, our data could be explained on basis of the time-varying elastance concept (H. Suga, K. Sagawa, and A. A. Shoukas. Circ. Res. 32: 314-322, 1973). The intravascular and luminal (cavity) compartments both are assumed to be subject to a time-varying elastance. The time-varying luminal elastance is similar for isovolumic and isobaric beats. We assume that the elastance of the vascular compartment also behaves the same for these beats, and therefore coronary flow is affected similarly.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Regional myocardial flow heterogeneity explained with fractal networks.

There is marked heterogeneity in regional myocardial blood flow. To explain how the distribution of flow broadens with an increase in the spatial resolution of the measurement, we developed fractal models for vascular networks. A dichotomous branching network of vessels represents the arterial tree and connects to a similar venous network. A small difference in vessel lengths and radii between the two daughter vessels, with the same degree of asymmetry at each branch generation, predicts the dependence of the relative dispersion (mean +/- SD) on spatial resolution of the perfusion measurement reasonably well. When the degree of asymmetry increases with successive branching, a better fit to data on sheep and baboons results. When the asymmetry is random, a satisfactory fit is found. These models show that a difference in flow of 20% between the daughter vessels at a branch point gives a relative dispersion of flow of approximately 30% when the heart is divided into 100-200 pieces. Although these simple models do not represent anatomic features accurately, they provide valuable insight on the heterogeneity of flow within the heart.

Animals↗

PubMed2005

Ancestry explains the blunted ventilatory response to sustained hypoxia and lower exercise ventilation of Quechua altitude natives.

Andean high-altitude (HA) natives have a low (blunted) hypoxic ventilatory response (HVR), lower effective alveolar ventilation, and lower ventilation (VE) at rest and during exercise compared with acclimatized newcomers to HA. Despite blunted chemosensitivity and hypoventilation, Andeans maintain comparable arterial O(2) saturation (Sa(O(2))). This study was designed to evaluate the influence of ancestry on these trait differences. At sea level, we measured the HVR in both acute (HVR-A) and sustained (HVR-S) hypoxia in a sample of 32 male Peruvians of mainly Quechua and Spanish origins who were born and raised at sea level. We also measured resting and exercise VE after 10-12 h of exposure to altitude at 4,338 m. Native American ancestry proportion (NAAP) was assessed for each individual using a panel of 80 ancestry-informative molecular markers (AIMs). NAAP was inversely related to HVR-S after 10 min of isocapnic hypoxia (r = -0.36, P = 0.04) but was not associated with HVR-A. In addition, NAAP was inversely related to exercise VE (r = -0.50, P = 0.005) and ventilatory equivalent (VE/Vo(2), r = -0.51, P = 0.004) measured at 4,338 m. Thus Quechua ancestry may partly explain the well-known blunted HVR (10, 35, 36, 57, 62) at least to sustained hypoxia, and the relative exercise hypoventilation at altitude of Andeans compared with European controls. Lower HVR-S and exercise VE could reflect improved gas exchange and/or attenuated chemoreflex sensitivity with increasing NAAP. On the basis of these ancestry associations and on the fact that developmental effects were completely controlled by study design, we suggest both a genetic basis and an evolutionary origin for these traits in Quechua.

Adult↗

PubMed2002

Dynamics of cerebral blood flow regulation explained using a lumped parameter model.

The dynamic cerebral blood flow response to sudden hypotension during posture change is poorly understood. To better understand the cardiovascular response to hypotension, we used a windkessel model with two resistors and a capacitor to reproduce beat-to-beat changes in middle cerebral artery blood flow velocity (transcranial Doppler measurements) in response to arterial pressure changes measured in the finger (Finapres). The resistors represent lumped systemic and peripheral resistances in the cerebral vasculature, whereas the capacitor represents a lumped systemic compliance. Ten healthy young subjects were studied during posture change from sitting to standing. Dynamic variations of the peripheral and systemic resistances were extracted from the data on a beat-to-beat basis. The model shows an initial increase, followed approximately 10 s later by a decline in cerebrovascular resistance. The model also suggests that the initial increase in cerebrovascular resistance can explain the widening of the cerebral blood flow pulse observed in young subjects. This biphasic change in cerebrovascular resistance is consistent with an initial vasoconstriction, followed by cerebral autoregulatory vasodilation.

Blood Pressure↗

PubMed1994

Clinical tests explain blunted cortisol responsiveness but not mild hypercortisolism in amenorrheic runners.

To investigate mechanisms of blunted adrenocortical responsiveness to exercise and mild hypercortisolism in amenorrheic runners, adrenocorticotropic hormone [ACTH-(1-24) 0.25 mg Cortrosyn] stimulation tests were performed in the presence and absence of overnight dexamethasone (1 mg) suppression (DX and NDX condition, respectively) in six eumenorrheic sedentary women (ES), nine eumenorrheic runners (ER), and nine amenorrheic runners (AR). Before the NDX stimulation test, plasma cortisol was higher (P < 0.001) in AR than in ER and ES. The cortisol response to the NDX stimulation test was blunted (P < 0.001) in AR but reached similar (P > 0.7) peak levels in all groups. Dexamethasone suppressed (P < 0.001) cortisol to similar (P > 0.5) levels (approximately 20 nmol/l) in all groups. In AR, cortisol responses to the DX test were larger (P < 0.03) than to the NDX test and similar (P > 0.6) in the three groups, again reaching comparable (P > 0.8) peak levels. The blunted cortisol response to stimulation in AR in the presence of their mild hypercortisolism appears to be due to a normal limitation in maximal adrenal secretory capacity. Extrapituitary modulators of adrenal responsiveness to ACTH may explain the mild hypercortisolism observed in AR, but limitations of these tests prevent a central negative-feedback defect or an intrinsic adrenal abnormality from being excluded until results of additional studies with even lower doses of dexamethasone and submaximal doses of ACTH-(1-24) are available.

Adolescent↗

PubMed1997

Guinea pig pulmonary hypertension caused by cigarette smoke cannot be explained by capillary bed destruction.

Chronic exposure to cigarette smoke is known to produce pulmonary hypertension in humans and in animal models, but the etiology of this process is controversial. To evaluate whether alterations in the structure of the pulmonary capillary bed or the peribronchiolar arterioles could be correlated with the pulmonary arterial pressure (Ppa), we examined the pulmonary vasculature in guinea pigs that had developed pulmonary hypertension after being exposed to cigarette smoke for 6 mo. The smoke-exposed animals had a significant increased Ppa compared with the control (air-exposed) animals (14.4 +/- 2.4 vs. 9.9 +/- 0.9 cmH2O). In the smoke-exposed animals, there was an increased percentage of muscularized peribronchiolar arterioles (33.5 +/- 5.8% smoke exposed vs. 56.1 +/- 5.8% control), and the capillary diameter and density were significantly decreased in both the center and periphery of the lobule (center diameter 8.8 +/- 1.9, periphery diameter 10.0 +/- 2.0 microns, center density 79 +/- 5, and periphery density 84 +/- 4 in smoked exposed vs. center diameter 7.7 +/- 1.9, periphery diameter 8.6 +/- 2.0 microns, center density 73 +/- 6, and periphery density 77 +/- 6 in controls). Neither group showed any correlation between these values and the Ppa. We conclude that although chronic exposure to cigarette smoke produces alteration of the capillary bed and pulmonary arterioles secondary to emphysematous air-space enlargement, these structural findings cannot explain the increase in Ppa. It appears that pulmonary hypertension due to chronic cigarette smoke exposure is a result of a primary alteration of capillary or muscular arteriolar vascular structure but instead may be secondary to alterations of the dynamic properties of the vascular bed with subsequent increase in vascular resistance.

Animals↗

PubMed1999

Critical closing pressure explains cerebral hemodynamics during the Valsalva maneuver.

The Valsalva maneuver (VM), a voluntary increase in intrathoracic pressure of approximately 40 mmHg, has been used to examine cerebral autoregulation (CA). During phase IV of the VM there are pronounced changes in mean arterial blood pressure (MABP), pulse interval, and cerebral blood flow (CBF), but the changes in CBF are of a much greater magnitude than those seen in MABP, a finding to date attributed to either a delay in activation of the CA mechanism or the inability of this mechanism to cope with the size and speed of the blood pressure changes involved. These changes in CBF also precede those in MABP, a pattern of events not explained by the physiological process of CA. Measurements of CBF velocity (transcranial Doppler) and MABP (Finapres) were performed in 53 healthy volunteers (aged 31-80 yr). By calculating beat-to-beat values of critical closing pressure (CCP) during the VM, we have found that this parameter suddenly drops at the start of phase IV, providing a coherent explanation for the large increase in CBF. If CCP is included in the estimation of cerebrovascular resistance, a temporal pattern more consistent with an autoregulatory response to the MABP overshoot is also found. CCP is intricately involved in the control of CBF during the VM and should be considered in the assessment of CA.

Adult↗