| 1. |
- Postmus, I., et al.
(author)
-
Meta-analysis of genome-wide association studies of HDL cholesterol response to statins
- 2016
-
In: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 53:12, s. 835-45
-
Journal article (peer-reviewed)abstract
- Background In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Interindividual variation in HDL-C response to statins may be partially explained by genetic variation. Methods and results We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p<1x10(-4) from the 16 769 statin-treated participants in the first analysis stage were followed up in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (p<5x10(-8)) were between minor alleles at the CETP locus and greater HDL-C response to statin treatment. Conclusions Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels.
|
|
| 2. |
- Byberg, Liisa, et al.
(author)
-
Changes in physical activity are associated with changes in metabolic cardiovascular risk factors
- 2001
-
In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 44:12, s. 2134-2139
-
Journal article (peer-reviewed)abstract
- Aims/hypothesisTo investigate the effect of changes in physical activity on changes in metabolic cardiovascular risk factors and to investigate what factors affect the association between physical activity and cardiovascular mortality.MethodsOf the 1860 men who were 50 years of age and who were without pre-existing cardiovascular disease participating in a population-based study, 898 were re-examined 20 years later. Altogether 231 died from cardiovascular diseases during the follow-up (mean = 22.6 years). The examinations which the men underwent at 50 and 70 years of age included assessment of physical activity (self-reported at four alternative levels), anthropometry, measurements of fasting concentrations of glucose, specific insulin, proinsulin, split proinsulin and lipids.ResultsDuring the 20 years, 31 % increased their amount of physical activity while 51 % continued the same amount of exercise. Increased physical activity was associated with significant changes in several important metabolic variables, including fasting glucose, proinsulin and HDL cholesterol, independent of body weight changes. The risk of cardiovascular disease for men performing moderate, regular and athletic physical activity was 25 % (p = 0.127), 34 % (p = 0.022) and 71 % (p = 0.009) lower, respectively, compared with sedentary men. The association was attenuated by adjustment for baseline measurements of insulin, proinsulin and split proinsulin. Additional adjustment for other cardiovascular risk factors did not further attenuate the association.Conclusion/interpretationIncreased leisure time physical activity between the ages of 50 and 70 years, in the absence of active intervention, is associated with improved glucose, insulin and lipid metabolism in men. The concentrations of insulin, proinsulin and split proinsulin could mediate much of the association between a sedentary lifestyle and increased risk of cardiovascular mortality.
|
|
| 3. |
- Leon, D A, et al.
(author)
-
Failure to realise growth potential in utero and adult obesity in relation to blood pressure in 50 year old Swedish men.
- 1996
-
In: BMJ (Clinical Research Edition). - : BMJ. - 0959-8138 .- 1468-5833. ; 312:7028, s. 401-6
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To clarify the type of fetal growth impairment associated with increased blood pressure in adult life, and to establish whether this association is influenced by obesity and is mediated through impairment of insulin action.DESIGN: Cross sectional survey with retrospective ascertainment of size at birth from obstetric archives.SUBJECTS: 1333 men resident in Uppsala, Sweden, who took part in a 1970 study of coronary risk factors at age 50 and for whom birth weight was traced.MAIN OUTCOME MEASURES: Systolic and diastolic blood pressure at age 50.RESULTS: In the full study population for a 1000g increase in birth weight there was a small change in systolic blood pressure of -2.2mmHg (95% confidence interval -4.2 to - 0.3mmHg) and in diastolic blood pressure of -1.0mmHg (-2.2 to 0.1mmHg). Much stronger effects were observed among men who were born at term and were in the top third of body mass index at age 50, for whom a 1000g increase in birth weight was associated with a change of -9.1mmHg (-16.4 to-1.9mmHg) systolic and -4.2mmHg (-8.3 to -0.1mmHg) diastolic blood pressure. Men who were light at birth (<3250g) but were above median adult height had particularly high blood pressure. Adjustment for insulin concentrations reduced the associations of birth weight with systolic and diastolic blood pressure.CONCLUSIONS: A failure to realise growth potential in utero (as indicated by being light at birth but tall as an adult) is associated with raised adult blood pressure. Impaired fetal growth may lead to substantial increases in adult blood pressure among only those who become obese. Metabolic disturbances, possibly related to insulin resistance, may provide a pathway through which fetal growth affects blood pressure.
|
|
| 4. |
- Leon, D A, et al.
(author)
-
Reduced fetal growth rate and increased risk of death from ischaemic heart disease : cohort study of 15 000 Swedish men and women born 1915-29.
- 1998
-
In: BMJ (Clinical Research Edition). - : BMJ. - 0959-8138 .- 1468-5833. ; 317:7153, s. 241-5
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To establish whether fetal growth rate (as distinct from size at birth) is associated with mortality from ischaemic heart disease.DESIGN: Cohort study based on uniquely detailed obstetric records with 97% follow up over the entire life course and linkage to census data in adult life.SUBJECTS: All 14 611 babies delivered at the Uppsala Academic Hospital, Sweden, during 1915-29 followed up to end of 1995.MAIN OUTCOME MEASURES: Mortality from ischaemic heart disease and other causes.RESULTS: Cardiovascular disease showed an inverse association with birth weight for both men and women, although this was significant only for men. In men a 1000 g increase in birth weight was associated with a proportional reduction in the rate of ischaemic heart disease of 0.77 (95% confidence interval 0.67 to 0.90). Adjustment for socioeconomic circumstances at birth and in adult life led to slight attenuation of this effect. Relative to the lowest fourth of birth weight for gestational age, mortality from ischaemic heart disease in men in the second, third, and fourth fourths was 0.81 (0.66 to 0.98), 0.63 (0.50 to 0.78), and 0.67 (0.54 to 0.82), respectively. The inclusion of birth weight per se and birth weight for gestational age in the same model strengthened the association with birth weight for gestational age but removed the association with birth weight.CONCLUSION: This study provides by far the most persuasive evidence of a real association between size at birth and mortality from ischaemic heart disease in men, which cannot be explained by methodological artefact or socioeconomic confounding. It strongly suggests that it is variation in fetal growth rate rather than size at birth that is aetiologically important.
|
|
| 5. |
- Lithell, H O, et al.
(author)
-
Relation of size at birth to non-insulin dependent diabetes and insulin concentrations in men aged 50-60 years.
- 1996
-
In: BMJ (Clinical Research Edition). - : BMJ. - 0959-8138 .- 1468-5833. ; 312:7028, s. 406-10
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To establish whether the relation between size at birth and non-insulin dependent diabetes is mediated through impaired beta cell function or insulin resistance.DESIGN: Cohort study.SETTING: Uppsala, Sweden.SUBJECTS: 1333 men whose birth records were traced from a cohort of 2322 men born during 1920-4 and resident in Uppsala in 1970.MAIN OUTCOME MEASURES: Intravenous glucose tolerance test at age 50 years and non-insulin dependent diabetes at age 60 years.RESULTS: There was a weak inverse correlation (r=-0.07, P=0.03) between ponderal index at birth and 60 minute insulin concentrations in the intravenous glucose tolerance test at age 50 years. This association was stronger (r=-0.19, P=0.001) in the highest third of the distribution of body mass index than in the other two thirds (P=0.01 for the interaction between ponderal index and the body mass index). Prevalence of diabetes at age 60 years was 8% in men whose birth weight was less than 3250 g compared with 5% in men with birth weight 3250 g or more (P=0.08; 95% confidence interval for difference -0.3% to 6.8%). There was a stronger association between diabetes and ponderal index: prevalence of diabetes was 12% in the lowest fifth of ponderal index compared with 4% in the other four fifths (P=0.001; 3.0% to 12.6%).CONCLUSION: These results confirm that reduced fetal growth is associated with increased risk of diabetes and suggest a specific association with thinness at birth. This relation seems to be mediated through insulin resistance rather than through impaired beta cell function and to depend on an interaction with obesity in adult life.
|
|
| 6. |
- McGurnaghan, S. J., et al.
(author)
-
Development and validation of a cardiovascular risk prediction model in type 1 diabetes
- 2021
-
In: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 64, s. 2001-2011
-
Journal article (peer-reviewed)abstract
- Aims/hypothesis We aimed to report current rates of CVD in type 1 diabetes and to develop a CVD risk prediction tool for type 1 diabetes. Methods A cohort of 27,527 people with type 1 diabetes without prior CVD was derived from the national register in Scotland. Incident CVD events during 199,552 person-years of follow-up were ascertained using hospital admissions and death registers. A Poisson regression model of CVD was developed and then validated in the Swedish National Diabetes Register (n = 33,183). We compared the percentage with a high 10 year CVD risk (i.e., >= 10%) using the model with the percentage eligible for statins using current guidelines by age. Results The age-standardised rate of CVD per 100,000 person-years was 4070 and 3429 in men and women, respectively, with type 1 diabetes in Scotland, and 4014 and 3956 in men and women in Sweden. The final model was well calibrated (Hosmer- Lemeshow test p > 0.05) and included a further 22 terms over a base model of age, sex and diabetes duration (C statistic 0.82; 95% CI 0.81, 0.83). The model increased the base model C statistic foam 0.66 to 0.80, from 0.60 to 0.75 and from 0.62 to 0.68 in those aged <40, 40-59 and >= 60 years, respectively (alp values <0.005). The model required minimal calibration in Sweden and had a C statistic of 0.85. Under current guidelines, >90% of those aged 20-39 years and 100% of those >= 40 years with type 1 diabetes were eligible for statins, but it was not until age 65 upwards that 100% had a modelled risk of CVD >= 10% in 10 years. Conclusions/interpretation A prediction tool such as that developed here can provide individualised risk predictions. This 10 year CVD risk prediction tool could facilitate patient discussions regarding appropriate statin prescribing. Apart from 10 year risk, such discussions may also consider longer-term CVD risk, the potential for greater benefits from early vs later statin intervention. the potential impact on quality of life of an early CVD event and evidence on safety, all of which could influence treatment decisions, particularly in younger people with type 1 diabetes.
|
|
