| 1. |
- Jujic, Amra, et al.
(författare)
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A genetic variant of the atrial natriuretic peptide gene is associated with left ventricular hypertrophy in a non-diabetic population - the Malmo preventive project study.
- 2013
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Ingår i: BMC Medical Genetics. - : BioMed Central. - 1471-2350. ; 14:64
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological studies have shown considerable heritability of blood pressure, thus suggesting a role for genetic factors. Previous studies have shown an association of a single nucleotide polymorphism rs5068 on the NPPA locus gene with higher levels of circulating atrial natriuretic peptide as well as with lower intra individual blood pressure, but up to date, no association between rs5068 and cardiac organ damage, i.e. left ventricular hypertrophy, has been accounted for in humans. Our sought explore if rs5068 is associated with left ventricular hypertrophy as measured by echocardiographic examination in a non-diabetic population. METHODS: 968 non-diabetic individuals from the Malmo Preventive Project (mean age 67 years; 31% women) were genotyped and examined with echocardiography. Logistic regression was used to adjust for covariates. RESULTS: The minor allele of rs5068 was associated with decreased prevalence of left ventricular hypertrophy (p = 0.021) after adjustment for sex and age. In the multivariate logistic analysis including; age, sex, systolic blood pressure, antihypertensive and/or cardioprotective treatment, body mass index and fasting plasma glucose, the association of rs5068 with left ventricular hypertrophy was, as expected, attenuated (p = 0.061). CONCLUSION: In a non-diabetic population, the minor allele of rs5068 was associated with lower left ventricular mass. These findings suggest that rs5068, or genetic variants in linkage disequilibrium, might affect susceptibility to left ventricular hypertrophy and support the possible protective role of natriuretic peptides.
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| 2. |
- Leosdottir, Margrét
(författare)
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Age and gender differences in risk factor burden, myocardial dysfunction and cardiovascular events in relation to glucose metabolism
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The risk of cardiovascular disease (CVD) and heart failure (HF) among individuals with diabetes is at least two times greater than in non-diabetic subjects. However, the excess risk of CVD in diabetic subjects seems to decrease with age. As the majority of patients with diabetes, CVD and HF are elderly it is important to establish the extent to which the associations between these conditions differ from those in younger populations. The overall aim of the work presented in this thesis was to study gender-related associations between glucose metabolism and myocardial dysfunction, risk factor burden and CVD events in middle-aged and elderly subjects. The hypothesis tested was that similar associations would be observed in elderly as in younger populations, although the associations would be weaker with advancing age. Data from two population-based cohort studies were used: MPP-RES (Sweden: n=18,238, mean age 69+/-6 years, range 57-86 years) and AGES-RS (Iceland: n=5,764, mean age 76+/-6 years, range 67-95). In Paper I the associations between echocardiographic indices of left ventricular diastolic dysfunction (LVDD), LV mass index (LVMI) and glucometabolic status were studied in echocardiography subcohorts from the two cohort studies (MPP-RES n=1,792; AGES-RS n=841). The MPP-RES cohort was divided into two age groups: middle-aged (57-69 years) and elderly subjects (70-80 years). All subjects were grouped according to fasting glucose level (FG, mmol/l): =<5.0; 5.1-5.5; 5.6-6.0 and 6.1-6.9 (pre-diabetic range) and >=7.0 (new-onset diabetes) and established diabetes, and trends between the groups were assessed. Few and inconsistent associations were observed in the AGES-RS cohort and in the elderly group in the MPP-RES cohort between increasing glucometabolic impairment and measures of LVDD. These observations are in contrast to previous findings in younger subjects as well as the present findings in the middle-aged group in the MPP-RES cohort, where a significant association was found between increasing LVDD and increasing glucometabolic impairment. It was concluded that changes in LV diastolic function may be more related to age than glucose metabolism in elderly subjects. In Paper II possible associations between N-terminal pro-B-type natriuretic peptide (Nt-proBNP) and FG as a continuous variable and in FG groups (as in Paper I) were assessed in the MPP-RES echocardiography subcohort. A positive correlation was found between Nt-proBNP and FG among middle-aged men. A positive correlation was also observed among elderly men, albeit non-significant. A non-significant negative correlation was observed among women in both age groups. The results indicate that caution should probably be exercised when interpreting Nt-proBNP values in subjects with impaired glucose metabolism. In Paper III the strength of the correlation between glucometabolic impairment, CVD risk factor burden and self-rated health (SRH), in middle-aged and elderly groups in the whole MPP-RES cohort (n=18,238) was compared. Correlations between increasing glucometabolic impairment and CVD risk factor burden and the proportion of subjects reporting poor SRH increased for both men and women in both age groups (p-trend <0.0001 for all). The slope of the trend curve with increasing CVD risk factor burden was significantly steeper for elderly women than for elderly men (p-interaction=0.002). The slope of the trend curve for poor SRH was significantly steeper for middle-aged than for elderly men (p-interaction=0.005), while no difference was observed between the age groups in the women. These results indicate lifelong CVD risk factor clustering and poorer SRH with increased glucometabolic impairment, being somewhat more pronounced in elderly women than in elderly men. Finally, in Paper IV we examined whether the previously observed age-related reduction in excess CVD risk for diabetic compared to non-diabetic subjects also applies to pre-diabetic conditions. The MPP-RES cohort was followed for 4.1+/-1.3 years during which 1,296 CVD events occurred. Subjects were grouped by FG, gender and age, as previously. The hazard ratios for CVD events increased with increasing FG among middle-aged men and women. No comparable increase was observed among elderly subjects, where men with FG =<5.0-6.9 and women with FG =<5.0-6.0 had HRs close to 1.0. The B-coefficients for interaction between age groups and intergroup trends were -0.17 (unadjusted p=0.01) and -0.15 (fully adjusted p=0.03) for men, and -0.13 (p=0.27) for women (irrespective of adjustment). It was concluded that FG values within the upper pre-diabetic range conveyed less excess risk of CVD events among elderly than middle-aged men and women.
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| 3. |
- Leosdottir, Margrét, et al.
(författare)
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Age and gender differences in the association between Nt-proBNP and glucometabolic disturbances.
- 2011
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Ingår i: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 45, s. 294-300
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Tidskriftsartikel (refereegranskat)abstract
- Abstract Objectives. Glucometabolic disturbances are associated with myocardial dysfunction. Brain natriuretic peptides (BNP) are used for detecting myocardial dysfunction in clinical practice. However, studies on elderly subjects and gender-specific analyses are sparse. Design. We examined cross-sectional associations between Nt-proBNP and 1) fasting plasma glucose (FPG), and 2) categories of glucometabolic disturbances, in middle-aged and older subjects (1266 men, 526 women), applying multivariate linear regression analysis. Results. FPG was positively correlated with Nt-proBNP among middle-aged men (p = 0.04) and negatively albeit non-significantly (p = 0.1) among middle-aged women. Weaker non-significant correlations were seen among older subjects. Middle-aged men with new-onset and prevalent diabetes had higher Nt-proBNP than the reference group (FPG ≤5.0 mmol/L): 9.53 (p = 0.002) and 8.23 (p = 0.02) vs. 5.71 pmol/L. No differences in Nt-proBNP between categories of glucometabolic disturbance were observed among older men or women. Conclusions. The results indicate an age- and gender difference in the ability of Nt-proBNP to identify myocardial dysfunction in relation to glucometabolic disturbances. Therefore, Nt-proBNP should be used with caution as a general surrogate marker for myocardial dysfunction in this setting.
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| 4. |
- Leosdottir, Margret, et al.
(författare)
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Myocardial structure and function by echocardiography in relation to glucometabolic status in elderly subjects from 2 population-based cohorts : a cross-sectional study
- 2010
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Ingår i: American Heart Journal. - : Elsevier BV. - 1097-6744 .- 0002-8703. ; 159:3, s. 4-420
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Left ventricular (LV) diastolic dysfunction has been associated with impaired glucometabolic status. However, studies of older subjects are lacking. We examined associations between echocardiographic indices of LV diastolic function and LV mass index (LVMI) and glucometabolic status among middle-aged and elderly subjects free from heart disease, hypothesizing that the associations would be comparative to younger cohorts.METHODS: We examined the Age Gene/Environment Susceptibility Reykjavik Study (Iceland; n = 607, 76 +/- 6 years) and the Malmö Preventive Project Re-Examination Study (MPP-RES) cohorts (Sweden; n = 1,519, 67 +/- 6 years), evaluating associations with multivariable regression analysis.RESULTS: In the Age Gene/Environment Susceptibility Reykjavik Study, LVMI was positively correlated with glycosylated hemoglobin (HbA1c) (P = .001). Otherwise, echocardiographic variables were not associated with glucometabolic status. In the MPP-RES, LVMI increased with increasing glucometabolic disturbance among both older (70-80 years) and middle-aged (57-69 years) subjects. Among older subjects, HbA1c was positively correlated with 2 variables reflecting LV diastolic function: late transmitral peak flow velocity (A) (P = .001) and early transmitral peak flow velocity (E)/early diastolic peak tissue velocity (Em) (P = .046). In middle-aged MPP-RES subjects, increasing glucometabolic disturbance was correlated with increasing late diastolic peak tissue velocity (Am) (P = .002) and, after age adjustment, with increasing A (P = .001) and decreasing Em/Am (P = .009). With age adjustment, Am and A were positively correlated with fasting glucose and HbA1c.CONCLUSIONS: Contrary to our hypothesis, in 2 independent cohorts of older individuals, associations between glucometabolic status and LV diastolic function were generally weak. These contrast with previous reports, as well as with observations among middle-aged subjects in the present study. Changes in LV diastolic function may be more age-related than associated with glucose metabolism in older subjects.
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| 5. |
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| 6. |
- Leosdottir, Margrét, et al.
(författare)
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The association between glucometabolic disturbances, traditional cardiovascular risk factors and self-rated health by age and gender: A cross-sectional analysis within the Malmo Preventive Project
- 2011
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 10:118
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Tidskriftsartikel (refereegranskat)abstract
- Background: The increased risk of cardiovascular disease (CVD) in diabetic compared to non-diabetic subjects seems to decrease with age. Whether this age-related reduction applies to CVD risk factors, and whether it is limited to established diabetes mellitus (DM) or also applies to pre-diabetic conditions are not well known. Methods: Using a cross-sectional design we compared the strength of the correlation between glucometabolic disturbances (by grouping), CVD risk factor burden and self-rated health, in two age groups: middle-aged (57-69 years) and older (70-86 years) subjects, (63% men), participating in the Malmo Preventive Project Re-examination Study (n = 18,238). Simple (unadjusted) logistic regression analysis was applied to estimate between-group differences and trends. Interaction analysis was applied to estimate differences between age groups. Results: CVD risk factor burden and the proportion of subjects reporting poor self-rated health increased with increasing glucometabolic disturbance for men and women in both age groups (p-trend < 0.0001 for all). The slope of the trend curve with increasing CVD risk factor burden was significantly steeper for older women than for older men (p-interaction = 0.002). The slope of the trend curve for poor self-rated health was significantly steeper for middle-aged than for older men (p-interaction = 0.005), while no difference was observed between the age groups among women (p-interaction = 0.97). Conclusions: We found no reduction in risk factor accumulation with increasing glucometabolic disturbance between middle-aged and older subjects. Our results indicate life-long CVD risk factor clustering with increased glucometabolic disturbance, and suggest that previously observed age-related reduction in excess CVD risk for subjects with DM might be due to a survival bias. However, our observations indicate more pronounced risk factor clustering and worse self-rated health with increased glucometabolic disturbance in older women than in older men.
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| 7. |
- Nilsson, Peter, et al.
(författare)
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Telomeres and cardiovascular disease risk: an update 2013.
- 2013
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Ingår i: Translational Research. - : Elsevier BV. - 1878-1810 .- 1931-5244. ; 162:6, s. 371-380
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Tidskriftsartikel (refereegranskat)abstract
- Leukocyte telomere length (LTL) has been regarded as a potential marker of biologic aging because it usually shortens in a predictable way with age. Recently, a growing interest in cardiovascular aging has led to a number of new epidemiologic studies investigating LTL in various disease conditions. Some methodological problems exist because there are different methods available to determine LTL, and standardization is much needed. For example, in the majority of studies, patients with early-onset coronary heart disease have been shown to have shorter LTL. In addition, patients with diabetes mellitus complications tend to have shorter LTL than control subjects. On the other hand, increased left ventricular hypertrophy or mass is associated with longer LTL, and studies investigating hypertension have reported both shorter and longer LTL than found in normotensive control subjects. There is, therefore, a need for longitudinal studies to elucidate these complicated relationships further, to provide estimations of telomere attrition rates, and to overcome analytical problems when only cross-sectional studies are used. The understanding of cardiovascular aging and telomere biology may open up new avenues for interventions, such as stem cell therapy or agents that could retard this aging process over and beyond conventional risk factor control.
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| 8. |
- Popov, Sergej, et al.
(författare)
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Salt-inducible kinase 1 influences Na+,K+-ATPase activity in vascular smooth muscle cells and associates with variations in blood pressure
- 2011
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 29:12, s. 2395-2403
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES:Essential hypertension is a complex condition whose cause involves the interaction of multiple genetic and environmental factors such as salt intake. Salt-inducible kinase 1 (SIK1) is a sucrose-nonfermenting-like kinase isoform that belongs to the AMPK (5' adenosine monophosphate-activated protein kinase) family. SIK1 activity is increased by high salt intake and plays an essential role in regulating the plasma membrane Na(+),K(+)-ATPase. The objective of this study was to examine whether SIK1 is present in vascular smooth muscle cells (VSMCs) and endothelial cells, whether it affects VSMC Na(+),K(+)-ATPase activity and whether human SIK1 (hSIK1) represents a potential candidate for blood pressure regulation.METHODS:Localization of SIK1 was performed using immunohistochemistry, mRNA and western blot. Functional assays (Na(+),K(+)-ATPase activity) were performed in VSMCs derived from rat aorta. Genotype-phenotype association studies were performed in three Swedish and one Japanese population-based cohorts.RESULTS:SIK1 was localized in human VSMCs and endothelial cells, as well as a cell line derived from rat aorta. A nonsynonymous single nucleotide polymorphism in the hSIK1 gene exon 3 (C→T, rs3746951) results in the amino acid change (15)Gly→Ser in the SIK1 protein. SIK1-(15)Ser was found to increase plasma membrane Na(+),K(+)-ATPase activity in cultured VSMC line from rat aorta. Genotype-phenotype association studies in three Swedish and one Japanese population-based cohorts suggested that T allele (coding for (15)Ser) was associated with lower blood pressure (P = 0.005 for SBP and P = 0.002 for DBP) and with a decrease in left ventricular mass (P = 0.048).CONCLUSION:The hSIK1 appears to be of potential relevance within VSMC function and blood pressure regulation.
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