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Biomedical subjects

Timo Strandberg

Publications and source records attributed to Timo Strandberg.

18 recordsLinked to original sources
PubMed2026

Genetic determinants of childhood blood pressure and heart rate in relation to adult health outcomes: the consortium of childhood blood pressure.

BACKGROUND AND AIMS: To elucidate the genetic architecture of blood pressure (BP) and heart rate (HR) during early life and assess their potential relevance to adult health outcomes. METHODS: The largest genome-wide association study (GWAS) meta-analyses to date of childhood systolic BP, diastolic BP, pulse pressure, and mean arterial pressure (n = 28 425) and HR (n = 22 565) were conducted in children of European ancestry aged 4-17 years. Follow-up analyses included comparisons with adult GWAS results, polygenic risk score (PRS) analyses in independent cohorts of diverse ancestries, and a phenome-wide association study in the UK Biobank. RESULTS: Eight genome-wide significant loci were identified for childhood BP (KIAA2013, CACNB2, PLCE1, PAX2, COL4A2, RP11-236L14.1, CFDP1, TPX2) and three loci for childhood HR (CCDC141, ACHE, MYH6); all novel in children but previously reported in adults. Childhood PRSs explained up to 1.6% of BP variance and 5.2% of HR variance among children of European ancestry. Genetic correlations between childhood and adulthood BP traits were moderate (rg = 0.4-0.7), suggesting age-specific genetic effects on BP. In the UK Biobank, higher childhood BP PRS levels were significantly associated with a broad range of adult health outcomes, particularly cardiometabolic outcomes such as hypertension, angina, myocardial infarction, and cardiovascular disease-related mortality. CONCLUSIONS: These findings advance the understanding of the genetic architecture of childhood BP and HR and provide compelling genetic evidence linking childhood BP to a broad spectrum of adult health outcomes-particularly cardiometabolic conditions-which may inform targeted prevention strategies from a young age.

Humans↗
PubMed2006

Source estimation of spontaneous MEG oscillations in mild cognitive impairment.

Mild cognitive impairment (MCI) is a memory disorder often preceding Alzheimer's disease (AD). AD has been shown to be associated with abnormal generation of spontaneous electromagnetic activity. We investigated whether the cortical generation of spontaneous brain oscillations in MCI shows changes resembling those observed in AD. A minimum current estimates algorithm was applied to identify cortical sources of magnetoencephalographic (MEG) spontaneous brain oscillations in male MCI patients with a clear memory disorder and in healthy elderly controls. This data was subsequently compared to a male subsample of AD patients from an earlier study. While there were clear oscillatory abnormalities in AD patients, there was no evidence of significant changes in the alpha source distribution in MCI patients as compared to healthy controls. Deficits in the distribution of oscillatory sources in the resting state are thus likely to occur at later stages of cognitive impairment than MCI.

Aged↗
PubMed2006

Muscle symptoms associated with statins: a series of twenty patients.

The aim of this study was to examine the clinical profile of statin-induced myalgia in patients with no apparent predisposing factors. Patients who reported muscle complaints that limited daily functioning during statin use were prospectively identified among the patients of Kuusankoski District Hospital and its catchment area, a population of about 100,000, between January 2003 and July 2004. Twenty patients in whom the muscle complaints were probably attributable to the use of a statin were included in this series. There were no cases of severe myopathy or rhabdomyolysis, and the highest creatine kinase value observed was only about 1900 U/l. Of the 18 patients that were evaluable for creatine kinase level, 5 (28%) did not exhibit elevation of creatine kinase and 6 (33%) showed a minor increase only. Following discontinuation of the statin, resolution of symptoms and normalisation of creatine kinase occurred in 11 of the 13 patients with elevated creatine kinase value as well as muscle complaints. Statins may cause clinically important muscle symptoms without inducing a marked creatine kinase elevation.

Adult↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2006

[Not Available].

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Journal Article↗
PubMed2005

CYP3A5 genotype is associated with diagnosis of hypertension in elderly patients: data from the DEBATE Study.

OBJECTIVE: The aim of this study was to address the presently controversial question of whether cytochrome P450 (CYP) 3A5 polymorphism is associated with hypertension. METHOD: We studied 373 elderly (age > or =75 years) Finnish (Caucasian) patients from the ongoing DEBATE (Drugs and Evidence Based Medicine in the Elderly) trial. The patients were classified into those with a history of hypertension (n = 229) and those without a history of hypertension (n = 144) on the basis of a detailed questionnaire on each patient's medical history and an interview. The patients were genotyped for the CYP3A5 6986A/G single nucleotide polymorphism (SNP) [CYP3A5*1/*3 alleles]. RESULTS: The proportion of individuals with the CYP3A5*1/*3 genotype, i.e. CYP3A5 expressors, was significantly higher among patients with a diagnosis of hypertension than among patients without (18.3% vs 9.0%, p = 0.016). The corresponding odds ratio was 2.26 (95% CI 1.17, 4.38). The allele and genotype frequencies for the two control SNPs, ABCB1 (MDR1) 3435C/T and SLCO1B1 521T/C, did not differ between the two groups. CONCLUSION: This work lends support to the theory that the polymorphic CYP3A5 enzyme may be involved in regulation of blood pressure. The possible role of CYP3A5 as a genetic contributor to hypertension susceptibility warrants further study.

Aged↗
PubMed2004

Left ventricular hypertrophy and blood pressure as predictors of cognitive decline in old age.

BACKGROUND AND AIMS: The relationships between blood pressure (BP) and cognition are complex and are still partly unclear. The impact of history of hypertension, present BP levels, and left ventricular hypertrophy (LVH) on cognition was investigated in a 10-year follow-up study of an aged population. METHODS: The population-based sample consisted of 75-, 80- and 85-year-old individuals at baseline (N=650). Their history of hypertension was investigated, and present BP values were recorded several times. Echocardiographic examinations were performed twice at 3-year intervals, and electrocardiography (ECG) at entry. Cognitive function was assessed by the Mini-Mental State Examination (MMSE) at baseline and at 10 years, and by the Clinical Dementia Rating (CDR) at baseline, at 1, 5 and 10 years. RESULTS: At baseline, elderly individuals with impaired cognition or dementia had lower BP, but thicker left ventricle posterior wall (LVPW), greater cardiac mass, and more often signs of LVH in ECG than those without cognitive deficits. Echocardiographic LVH, but not BP, predicted cognitive decline in a 5-year follow-up. Patients who died demented within 5 years were characterized by low BP and thin LVPW. Baseline BP and echocardiographic variables were not significantly different between those who had and had not cognitive decline at 10 years, but declining BP tended to precede cognitive deficits. CONCLUSIONS: Results indicate that, the closer cognitive decline, the lower the BP, and suggest that, although LVH is a risk factor of cognitive decline, it loses its predictive value in old age.

Aged↗
PubMed2004

Effect of 12-month statin therapy on antioxidant potential of LDL and serum antioxidant vitamin concentrations.

BACKGROUND: Statins are known to cause short-term reduction in serum lipid-soluble antioxidant concentrations, but their long-term effects are not known. AIM: We randomised 104 subjects with CHD and hypercholesterolaemia to receive either atorvastatin or simvastatin treatment for 52 weeks and measured the antioxidant potential of LDL and serum antioxidant vitamin concentrations. METHOD: Initial daily dose for both statins was 20 mg. RESULTS: LDL antioxidant capacity and serum alpha-tocopherol, gamma-tocopherol and beta-carotene concentrations decreased by 22%-35% with both statins during the first 12 weeks' therapy (P < 0.01 for all). After 52 weeks' therapy, the concentrations of serum gamma-tocopherol in the simvastatin group and serum beta-carotene in both treatment groups returned to baseline levels, while the concentrations of serum gamma-tocopherol in the atorvastatin group and LDL anti-oxidant capacity and serum alpha-tocopherol in both treatment groups remained reduced (P < 0.001 for all). The LDL antioxidant capacity:LDL-cholesterol and the serum alpha-tocopherol:LDL-cholesterol ratios were significantly elevated with both statins after 12 and 52 weeks (P < 0.001 for all). Statistically significant increases were also observed for corresponding ratios of the less abundant vitamins gamma-tocopherol and beta-carotene. CONCLUSIONS: Some of the decreases in serum lipid soluble antioxidant vitamins reported in short-term statin interventions may become attenuated when therapy continues longer. The relative antioxidant capacity of LDL particles increased during the 52-week treatment, suggesting that the oxidation resistance of LDL particles did not become impaired and that their atherogenicity did not increase.

Atorvastatin↗
PubMed2004

Lipid-lowering response to statins is affected by CYP3A5 polymorphism.

Individuals expressing the polymorphic CYP3A5 enzyme might show a more than average efficiency in the metabolism of lovastatin, simvastatin and atorvastatin. We studied whether the expression of CYP3A5 is associated with an impaired lipid-lowering response to statins in 69 Caucasian patients. Lovastatin, simvastatin and atorvastatin were significantly less effective in CYP3A5 expressors than in non-expressors. The mean serum total cholesterol concentration at 1 year was 23% higher (P = 0.0014) and the mean serum low-density lipoprotein cholesterol concentration was 24% higher (P = 0.036) in subjects possessing the CYP3A5*1 allele (CYP3A5 expressors, n = 7) than in subjects homozygous for the CYP3A5*3 allele (non-expressors, n = 39). The mean percentage reduction in serum total cholesterol from baseline was significantly smaller in CYP3A5 expressors than in non-expressors (17% versus 31%, P = 0.026). No association between hypolipidemic efficacy and CYP3A5 polymorphism was observed among 23 subjects taking statins that are not dependent on CYP3A5 (fluvastatin, pravastatin). These findings suggest that CYP3A5 may be a genetic determinant of interindividual differences in response to certain statins.

Aged↗
PubMed2003

Benefits of optimising drug treatment in home-dwelling elderly patients with coronary artery disease.

Coronary artery disease (CAD) is prevalent in the elderly and often leads to disability. Consequently, strategies for optimising the prevention and treatment of CAD in the elderly are important from both the individual and societal perspectives. Although it is common knowledge that the elderly are heavy consumers of drugs, there is evidence to show that there is under-prescribing of evidence-based medical therapies in the home-dwelling elderly coronary patient and there may be overuse of some non-evidence-based (antioxidants) and purely symptomatic treatments. In particular, aspirin (acetylsalicylic acid), beta-adrenoceptor antagonists, ACE inhibitors and HMG-CoA reductase inhibitors are under-utilised. Although the evidence base is largely drawn from trials including patients younger than 75 years, it is reasonable to assume that the data applies to patients aged over 75 years and that better use of evidence-based medicines would provide benefits to the home-dwelling aged patient. Evidence from the few multifactorial studies available suggest possible benefits including reduction of cardiovascular events, less disability and better quality of life in old age. At the societal level, this would be reflected in fewer hospitalisations and institutionalisations, which means decreased cost of elderly care.

Adrenergic beta-Antagonists↗
PubMed2002

[ASA therapy or not?].

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Anti-Inflammatory Agents, Non-Steroidal↗