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1.  Common non-synonymous substitutions in SLCO1B1 predispose to statin intolerance in routinely treated individuals with type 2 diabetes: A Go-DARTS study 
SLCO1B1 gene variants are associated with severe statin-induced myopathy. We examined whether these variants are also associated with general statin intolerance in a large population of patients with type 2 diabetes prescribed statins as part of routine clinical care.
4196 individuals were genotyped for rs4149056 (Val174Ala) and rs2306283 (Asp130Asn). Intolerance was defined by serum biochemistry and statin discontinuation, switching or dose reduction. Ala174 was associated with higher intolerance (OR=2.05, p=0.043), while Asp130 was associated with lower intolerance (OR=0.71, p= 0.026). Ala174 was associated with a reduced LDLc response (p=0.01) and 130D was associated with a greater LDLc response to statins (p=0.048) as previously reported, however this association was not present when intolerant individuals were removed.
This study suggests that common genetic variants, selected for an extreme phenotype of statin-induced myopathy also predispose to more common milder statin intolerance and may, for this reason, impact on lipid-lowering efficacy.
PMCID: PMC3353487  PMID: 21178985
2.  Sudden unexpected death in heart failure may be preceded by short term, intraindividual increases in inflammation and in autonomic dysfunction: a pilot study 
Heart  2004;90(11):1263-1268.
Objective: To see whether sudden unexpected death in chronic heart failure is preceded by intraindividual worsening in inflammation and in ECG criteria.
Design and setting: Prospective cohort study conducted in the community.
Patients: 34 patients with chronic heart failure were studied. Their mean (SD) age was 68 (8) years, 29 were men, mean (SD) left ventricular ejection fraction was 29 (9)%, and they were in New York Heart Association functional class II (n  =  20), III (n  =  11), and IV (n  =  3). The patients were examined monthly over 24 months, with sequential measurement of C reactive protein and neutrophil counts and 24 hour ambulatory ECG monitoring measuring heart rate variability, mean heart rate, and arrhythmias. Intraindividual changes in these parameters were related to subsequent cardiac deaths.
Results: During follow up, nine patients died: five patients had a sudden unexpected death (SUD) and four died of progressive heart failure (PHF). There were significant intraindividual changes in neutrophil counts (p  =  0.02), C reactive protein (p  =  0.039), and heart rate variability (p ⩽ 0.018) in those who died of SUD and PHF. In contrast no significant changes were seen in ventricular extrasystoles, ventricular tachycardia episodes, brain natriuretic peptide, or aldosterone in the SUD group, but all of these parameters did increase as expected in those who died of PHF.
Conclusions: This is preliminary evidence that SUD may be preceded by intraindividual increases in both inflammation and autonomic dysfunction. Both may be causal in genesis but, even if they are not, intraindividual increases in either may be convenient markers to identify patients at high risk of impending SUD. Larger studies are needed to confirm the observation from this pilot study.
PMCID: PMC1768533  PMID: 15486117
chronic heart failure; heart rate variability; C reactive protein; sudden cardiac death
4.  Environmental tobacco smoke and lung function in employees who never smoked: the Scottish MONICA study 
OBJECTIVES—To investigate the relation between lung function in employees and exposure to environmental tobacco smoke (ETS) at work and elsewhere.
METHODS—Never smokers in employment (301) were identified from the fourth Scottish MONICA survey. They completed a self administered health record, which included details of exposure to ETS, and attended a survey clinic for physical and lung function measurements, and for venepuncture for estimation of serum cotinine. Differences in lung function in groups exposed to ETS were tested by analysis of variance (ANOVA), the exposure-response relation by a linear regression model, and a case-control analysis undertaken with a logistic regression model.
RESULTS—Both men and women showed effects on forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC) from exposure to ETS—higher exposure going with poorer lung function. This was found at work, and in total exposure estimated from ETS at work, at home, and at other places. Linear regression showed an exposure-response relation, significant for ETS at work, total exposure, and exposure time/day, but not at home or elsewhere. Compared with those not exposed to ETS at work, those who were exposed a lot had a 254 ml (95% confidence interval (95% CI) 84 to 420) reduction in FEV1, and a 273 ml (60 to 480) reduction in FVC after adjusting for confounders. Although lung function was not significantly associated with serum cotinine in all the data, a significant inverse relation between cotinine concentration and FVC occurred in men who had had blood collected in the morning. Case-control analysis also showed a significant exposure-response relation between ETS, mainly at work, and lung function. A higher exposure measured both by self report and serum cotinine went with lower lung function.
CONCLUSION—The exposure-response relation shows a reduction in pulmonary function of workers associated with passive smoking, mainly at work. These findings endorse current policies of strictly limiting smoking in shared areas, particularly working environments.

Keywords: passive smoking; working environments; lung function
PMCID: PMC1740185  PMID: 11511742
5.  Plasma vitamin C and food choice in the third Glasgow MONICA population survey 
STUDY OBJECTIVE—To determine the contribution of different foods to the estimated intakes of vitamin C among those differing in plasma vitamin C levels, and thereby inform dietary strategies for correcting possible deficiency.
DESIGN—Cross sectional random population survey.
SETTING—North Glasgow, Scotland, 1992.
PARTICIPANTS—632 men and 635 women, aged 25 to 74 years, not taking vitamin supplements, who participated in the third MONICA study (population survey monitoring trends and determinants of cardiovascular disease).
MEASUREMENTS AND MAIN RESULTS—Dietary and sociodemographic information was collected using a food frequency and lifestyle questionnaire. Plasma vitamin C was measured in non-fasted venous blood samples and subjects categorised by cut points of 11.4 and 22.7 µmol/l as being of low, marginal or optimal vitamin C status. Food sources of dietary vitamin C were identified for subjects in these categories. Plasma vitamin C concentrations were compared among groups classified according to intake of key foods. More men (26%) than women (14%) were in the low category for vitamin C status; as were a higher percentage of smokers and of those in the older age groups. Intake of vitamin C from potatoes and chips (fried potatoes) was uniform across categories; while the determinants of optimal versus low status were the intakes of citrus fruit, non-citrus fruit and fruit juice. Optimal status was achieved by a combined frequency of fruit, vegetables and/or fruit juice of three times a day or more except in older male smokers where a frequency greater than this was required even to reach a marginal plasma vitamin C level.
CONCLUSION—Fruit, vegetables and/or fruit juice three or more times a day increases plasma vitamin C concentrations above the threshold for risk of deficiency.

Keywords: vitamin C; food frequency; fruit; vegetables
PMCID: PMC1731679  PMID: 10814656
6.  Comparison of the prediction by 27 different factors of coronary heart disease and death in men and women of the Scottish Heart Health Study: cohort study. 
BMJ : British Medical Journal  1997;315(7110):722-729.
OBJECTIVE: To compare prediction by 27 different factors in men and women of coronary heart disease events, coronary deaths, and deaths from all causes. DESIGN: Cohort study. SETTING: Scottish population study. SUBJECTS: In 1984-7 random sampling of residents aged 40-59 produced 11,629 men and women who generated survey clinic questionnaires, examination findings, and blood and urine specimens. MAIN OUTCOME MEASURES: Subsequent death, coronary artery surgery, and myocardial infarction. Risks were calculated for each category of factor or fifth of continuous variables. 27 factors were ranked by descending age adjusted hazard ratio of the top to bottom class in each factor, by sex and end point. RESULTS: Follow up averaged 7.6 years, during which the 5754 men had 404 coronary events, 159 coronary deaths, and 383 deaths and the 5875 women 177, 47, and 208 respectively. The rankings for factors for the three end points were mainly similar in men and women, although hazard ratios were often higher in women. Classical risk factors ranked better for predicting coronary risk than newer ones. Yet strong prediction of coronary risk was no guarantee of significant prediction of all cause mortality. Findings included an anomalous coronary protective role for type A behaviour in women; raised plasma fibrinogen as a strong predictor of all end points; and an unexpectedly powerful protective relation of dietary potassium to all cause mortality. CONCLUSIONS: These initial unifactorial rankings and comparisons must be interpreted with caution until potential interaction, confounding, and problems of measurement and causation are further explored.
PMCID: PMC2127508  PMID: 9314758
7.  Passive smoking by self report and serum cotinine and the prevalence of respiratory and coronary heart disease in the Scottish heart health study. 
STUDY OBJECTIVE--To explore the relationship between self reported environmental tobacco smoke exposure (or passive smoking), the serum cotinine concentration, and evidence of respiratory or coronary disease in men and women who have never smoked. DESIGN--Cross sectional random population survey identifying disease markers and relating them to measures of passive smoking. Disease markers were previous medical diagnoses, response to standard symptom questionnaires, and electrocardiographic signs. SETTING--Samples of men and women aged 40-59 years drawn from general practitioner lists in 22 local government districts of Scotland, between 1984 and 1986. PARTICIPANTS--A total of 786 men and 1492 women who reported never having smoked tobacco, and who had serum cotinine concentrations below 17.5 ng/ml, the cut off point for smoking "deceivers", took part. RESULTS--Fewer than one third of never smokers reported no recent exposure to environmental tobacco smoke and the same proportion had no detectable cotinine. Women had lower cotinine values than men but reported more exposure to smoke. The correlation between the measures of exposure was poor. Self-reported exposure showed strong, statistically significant, dose response relationships with respiratory symptoms and with the coronary disease markers. These relationships were weak or absent for serum cotinine, except for diagnosed coronary heart disease. Here the dose response gradient was as strong as that for self report, with an odds ratio of 2.7 (95% CI 1.3, 5.6) for the highest v the lowest exposure group, adjusted for age, housing tenure, total cholesterol, and blood pressure, and not explained by fibrinogen. CONCLUSIONS--The validity of different measures of tobacco smoke exposure needs further investigation. The gradient of diagnosed coronary heart disease with both self reported exposure and serum cotinine was, however, surprisingly strong, statistically significant, and unexplained by other factors. These findings reinforce current policies to limit passive tobacco smoke exposure.
PMCID: PMC1060097  PMID: 7798040
9.  Geographical clustering of risk factors and lifestyle for coronary heart disease in the Scottish Heart Health Study. 
British Heart Journal  1990;64(3):199-203.
A large cross sectional study, the Scottish Heart Health Study, of 10,359 men and women from 22 districts of Scotland was undertaken to try to explain the geographical variation of coronary heart disease mortality. Analysis by district showed that of the classic risk factors only cigarette smoking was strongly associated with heart disease mortality among both men and women. Mean diastolic blood pressure was weakly associated with rates among men and high density lipoprotein cholesterol showed a strong negative association among women. Total cholesterol showed a weak negative association with heart disease mortality, but, because the serum concentrations of cholesterol were uniformly high in all districts, a strong association with mortality would not be expected. In both men and women many dietary factors showed moderate or strong associations with mortality from coronary heart disease in a district--of these a low consumption of vitamin C was most notable. Other factors associated with heart disease included alcohol consumption and serum triglycerides among men, and obesity, physical activity, and serum triglycerides among women. Many factors associated with heart disease showed strong intercorrelations. Clustering of risk factors (including smoking, alcohol, and diet among men, and smoking, diet, and obesity among women) was associated with much of the regional variation in heart disease mortality in Scotland.
PMCID: PMC1024372  PMID: 2206712
10.  Urinary electrolyte excretion, alcohol consumption, and blood pressure in the Scottish heart health study. 
BMJ : British Medical Journal  1988;297(6644):329-330.
As part of a study of risk factors for coronary heart disease 24 hour urine collections were obtained from 7354 men and women aged 40-59 selected at random from 22 districts throughout Scotland (Scottish heart health study). The mean of two standardised measurements of blood pressure was related to the reported consumption of alcohol and measurements of height, weight, pulse rate, and electrolyte excretion. Several significant correlations were found with both systolic and diastolic pressure, but only the coefficients for age, body mass index, and pulse rate were greater than 0.1. Alcohol consumption showed a weak positive correlation with blood pressure in men. Sodium excretion showed a weak positive correlation with blood pressure in both sexes, and potassium excretion showed weak negative correlations. In multiple regression analysis age, pulse rate, body mass index, alcohol consumption, and potassium excretion had significant independent effects but sodium excretion did not. Although measuring blood pressure twice on one occasion and 24 hour urinary sodium excretion only once may have weakened any potential correlation, the most likely explantation of these results is that the relation between sodium and blood pressure in the population is weak and that potassium and alcohol are of greater importance.
PMCID: PMC1834048  PMID: 3416163

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