| 41. |
- Lind, Lars
(författare)
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A detailed lipoprotein profile in relation to intima-media thickness and echogenicity of three major arteries
- 2019
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 39:6, s. 415-421
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo investigate differences in risk‐factor profile, with special emphasis on detailed characterization of the lipoprotein profile, for intima‐media thickness (IMT) and echogenicity of the intima‐media complex (IM‐GSM) in three major arteries: the carotid, femoral and brachial arteries.MethodsIMT and IM‐GSM were measured by ultrasound in the carotid, femoral and brachial arteries in 778 subjects, all aged 75 years (50% women), in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, in which a detailed lipoprotein profile was also determined by nuclear magnetic resonance spectroscopy.ResultsFirst, IMT was considerably lower, and IM‐GSM higher, in the brachial artery compared to the other two arteries. Second, IMT and IM‐GSM in the arteries were related to each other. Third, significant different traditional risk‐factor profiles were seen for both IMT and IM‐GSM, with generally weaker relationships for IMT in the femoral and brachial arteries compared with the carotid artery. Fourth, the strength of associations between an atherogenic lipoprotein profile and IMT in the carotid artery was attenuated in the femoral artery and virtually absent in the brachial artery. Fifth, slightly different lipoprotein profiles were seen for IM‐GSM in the three arteries.ConclusionDifferences between the carotid, femoral and brachial artery IMT and IM‐GSM were seen regarding the traditional risk factors, as well as the lipoprotein profile.
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| 42. |
- Lind, Lars, et al.
(författare)
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Cardiometabolic Proteins Associated with Metabolic Syndrome
- 2019
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Ingår i: Metabolic syndrome and related disorders. - : Mary Ann Liebert Inc. - 1557-8518 .- 1540-4196. ; 17:5, s. 272-279
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although metabolic syndrome (MetS) was described in the late 80s, the molecular mechanisms underlying clustering of risk factors in certain individuals are not fully understood. The present study used targeted proteomics to establish cardiometabolic proteins related to all MetS components, thereby providing new hypotheses regarding pathways involved in the pathogenesis of MetS. Methods: In the EpiHealth study, 249 cardiometabolic proteins were measured by proximity extension assay (PEA) and related to the five MetS components [consensus-modified National Cholesterol Education Program (NCEP) criteria] in 2,444 participants aged 45-75 years (50% women). Results: Thirty-one proteins were associated with systolic blood pressure following adjustment for age and sex (P < 0.000040, taking multiple testing into account). The corresponding number of proteins significantly associated with fasting glucose, waist circumference, high-density lipoprotein cholesterol, and serum triglycerides were 58, 132, 127, and 148. Twenty-two proteins were significantly related to all 5 MetS components, and of those, 20 were with MetS as a binary outcome (n = 600, 24% of the sample) following adjustment for age, sex, fat mass, and lifestyle factors (alcohol intake, smoking, education, and exercise habits). Conclusion: Using targeted proteomics, we identified 20 proteins reflecting a range of pathways, such as immunomodulation at different levels; regulation of adipocyte differentiation; lipid, carbohydrate, and amino acid metabolism; or insulin-like growth factor signaling, to be strongly associated with MetS independently of fat mass and lifestyle factors. Whether some of these proteins are causally involved in the pathogenesis of clustering of multiple risk factors in the same individual remains to be investigated.
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| 43. |
- Lind, Lars, et al.
(författare)
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Change in left ventricular geometry over 10 years in the elderly and risk of incident cardiovascular disease
- 2019
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 37:2, s. 325-330
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Left ventricular hypertrophy (LVH) is related to a poor prognosis. We aimed to determine how left ventricular (LV) geometry changes over time, and how this relates to future cardiovascular disease.Methods: In the Prospective Study of the Vasculature in Uppsala Seniors study, 1016 individuals were investigated with echocardiography at age 70. This was repeated after 5 and 10 years. Incident cardiovascular disease (myocardial infarction, stroke, and heart failure, n = 163) was recorded over 10 years.Results: LV mass index (LVMI) and LV end-diastolic diameter (LVEDD) progressively increased over 10 years, while LV thickness declined (P< 0.0001 for all). Adjusting for traditional cardiovascular risk factors, LVMI at baseline, but not LVEDD, was significantly associated with incident cardiovascular disease [hazard ratio (HR) 1.02, 95% confidence interval 1.003-1.03, P = 0.019]. When adding the change in LVMI, or change in LVEDD, between ages 70 and 75 years to the models and using the time between 75 and 80 as follow-up (in total 82 incident cases), neither the change in LVMI nor the change in LVEDD were significant. Using updated information on LV geometric groups, an increased risk was seen for concentric LVH as compared with the normal group following adjustment for traditional risk factors (HR 2.29, P = 0.0014, 95% confidence interval 1.38-3.82). Eccentric LVH and concentric remodeling were not associated with a statistically significant increased risk of cardiovascular disease.Conclusion: In elderly individuals without myocardial infarction, a progressive dilatation of the LV was seen over 10 years. However, the LV dilation seen over time in this age group was not associated with a major increase in risk of future cardiovascular disease.
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| 44. |
- Lind, Lars
(författare)
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Genome-Wide Association Study of the Metabolic Syndrome in UK Biobank
- 2019
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Ingår i: Metabolic Syndrome and Related Disorders. - : MARY ANN LIEBERT, INC. - 1540-4196 .- 1557-8518. ; 17:10, s. 505-511
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Tidskriftsartikel (refereegranskat)abstract
- Background: The metabolic syndrome (MetS) is a description of a clustering of cardiometabolic risk factors in the same individual. Previous genome-wide association studies (GWASs) have identified 29 independent genetic loci linked to MetS as a binary trait. This study used data from UK biobank to search for additional loci.Methods: Using data from 291,107 individuals in the UK biobank, a GWAS was performed versus the binary trait MetS (harmonized NCEP criteria).Results: In a GWAS of MetS (binary) we found 93 independent loci with P < 5 x 10(-8), of which 80 were not identified in previous GWASs of MetS. However, the majority of those loci have previously been associated with one or more of the five MetS components. Of particular interest are the genes being related to MetS (binary) in this study, but not to any of the MetS components in past studies, such as WDR48, KLF14, NAADL1, GADD45G, and OR5R1, as well as the two loci that have been associated with all five MetS components in past studies, SNX10 and C5orf67. A pathway analysis of the 93 independent loci showed the immune system, transportation of small molecules, and metabolism to be enriched.Conclusion: This GWAS of the MetS in UK biobank identified several new loci being associated with MetS. Most of those have previously been found to be associated with different components of MetS, but several loci were found not previously linked to cardiometabolic disease.
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| 45. |
- Lind, Lars, et al.
(författare)
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Lifetime change in central and peripheral haemodynamics in relation to exercise capacity
- 2019
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Ingår i: Clinical Physiology and Functional Imaging. - : WILEY. - 1475-0961 .- 1475-097X. ; 39:4, s. 261-275
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Tidskriftsartikel (refereegranskat)abstract
- Exercise capacity as well as many resting central and peripheral haemodynamic features declines by age. We aimed to investigate which haemodynamic features change the most during life and which change in parallel to exercise capacity. We performed a maximal bicycle exercise test with gas exchange in 103 healthy subjects (24 young, 55 middle-aged and 24 elderly). Endothelial function, arterial compliance/stiffness and heart rate variability (HRV) were evaluated, and the myocardium and carotid arteries were investigated by ultrasound. Exercise capacity declined by almost 50% over the lifespan. Several markers reflecting arterial compliance/stiffness and HRV, as well as carotid intima-media thickness (IMT), showed lifetime impairments by >100%, while markers of LV systolic function, diastolic blood pressure and carotid artery blood flow showed only minor changes with age. The decline in exercise capacity clusters closely with many other variables measured during the exercise test, but also to resting vital capacity, left ventricular end-diastolic diameter and resting gas exchange (VO2, VCO2) to a lesser degree. Resting vital capacity was closely related to exercise capacity in the middle-aged group. We conclude that many of the resting markers of central and peripheral haemodynamics declined during life, in parallel to the decline in exercise capacity. However, some haemodynamic features, such as LF/HF ratio at HRV, stiffness index beta of the carotid artery, and heart rate reserve at the exercise test, showed a more exaggerated decline, indicating that those are not closely linked to exercise capacity.
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| 46. |
- Lind, Lars, et al.
(författare)
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Longitudinal effects of aging on plasma proteins levels in older adults : associations with kidney function and hemoglobin levels
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 14:2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: A targeted proteomics chip has been shown to be useful to discover novel associations of proteins with cardiovascular disease. We investigated how these proteins change with aging, and whether this change is related to a decline in kidney function, or to a change in hemoglobin levels.MATERIAL AND METHODS: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, including 1,016 participants from the general population aged 70 at baseline, 84 proteins were measured at ages 70, 75, 80. At these occasions, glomerular filtration rate (eGFR) was estimated and the hemoglobin levels were measured.RESULTS: Sixty-one of the 84 evaluated proteins changed significantly during the 10-year follow-up (multiple testing-adjusted alpha = 0.00059), most showing an increase. The change in eGFR was inversely related to changes of protein levels for the vast majority of proteins (74%). The change in hemoglobin was significantly related to the change in 40% of the evaluated proteins, with no obvious preference of the direction of these relationships.CONCLUSION: The majority of evaluated proteins increased with aging in adults. Therefore, normal ranges for proteins might be given in age-strata. The increase in protein levels was associated with the degree of reduction in eGFR for the majority of proteins, while no clear pattern was seen for the relationships between the proteins and the change in hemoglobin levels. Studies on changes in urinary proteins are warranted to understand the association between the reduction in eGFR and increase in plasma protein levels.
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| 47. |
- Lind, Lars
(författare)
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Population-based cardiovascular cohort studies in Uppsala
- 2019
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Ingår i: Upsala Journal of Medical Sciences. - : TAYLOR & FRANCIS LTD. - 0300-9734 .- 2000-1967. ; 124:1, s. 16-20
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Tidskriftsartikel (refereegranskat)abstract
- The first population-based cohort study in Uppsala with the aim to study cardiovascular disease was initiated in 1970 (ULSAM). This cohort of 2300 middle-aged men has since then been followed in a longitudinal fashion for almost 50 years. This study has been followed by the PIVUS study, investigating 1000 men and women at ages 70, 75, and 80. A very detailed examination has also been performed in 500 subjects aged 50 years, the POEM study. In recent years, a high-throughput study conducted in 13000 subjects has also been performed, named EpiHealth. Uppsala also collects data in 5,000 subjects in the nationwide SCAPIS study. Taken together, these cardiovascular-oriented studies constitute a very rich source for cardiovascular epidemiological research in Uppsala. This review summarizes the design of these studies and highlights some of the important results published based on data from these studies.
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| 48. |
- Lind, Lars, et al.
(författare)
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Proof of principle study of a detailed whole-body image analysis technique, "Imiomics", regarding adipose and lean tissue distribution
- 2019
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- This "proof-of-principle" study evaluates if the recently presented "Imiomics" technique could visualize how fat and lean tissue mass are associated with local tissue volume and fat content at high/unprecedented resolution. A whole-body quantitative water-fat MRI scan was performed in 159 men and 167 women aged 50 in the population-based POEM study. Total fat and lean mass were measured by DXA. Fat content was measured by the water-fat MRI. Fat mass and distribution measures were associated to the detailed differences in tissue volume and fat concentration throughout the body using Imiomics. Fat mass was positively correlated (r > 0.50, p < 0.05) with tissue volume in all subcutaneous areas of the body, as well as volumes of the liver, intraperitoneal fat, retroperitoneal fat and perirenal fat, but negatively to lung volume. Fat mass correlated positively with volumes of paravertebral muscles, and muscles in the ventral part of the thigh and lower limb. Fat mass was distinctly correlated with the fat content in subcutaneous adipose tissue at the trunk. Lean mass was positively related to the large skeletal muscles and the skeleton. The present study indicates the Imiomics technique to be suitable for studies of fat and lean tissue distribution, and feasible for large scale studies.
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| 49. |
- Lind, Lars, et al.
(författare)
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Proteomic profiling of endothelium-dependent vasodilation
- 2019
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Ingår i: Journal of Hypertension. - 0263-6352 .- 1473-5598. ; 37:1, s. 216-222
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Tidskriftsartikel (refereegranskat)abstract
- Objective: As endothelial dysfunction is an early event in atherosclerosis formation, we investigated if proteins previously related to cardiovascular disease also were related to endothelial function using a novel targeted proteomics approach.Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 850970, all aged 70 years), endothelium-dependent vasodilation (EDV) in the forearm was assessed by intraarterial infusion of acetylcholine. Flow-mediated vasodilation (FMD) was investigated in the brachial artery by ultrasound. The same investigations were carried out in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (n = 375-461, all aged 50 years). After strict quality control, 84 cardiovascular-related proteins measured by the proximity extension assay were studied in relation to EDV and FMD in PIVUS (discovery sample) and POEM (validation sample).Results: Of the 15 proteins being significantly related to EDV in PIVUS (false discovery rate < 0.025), seven could be replicated in POEM at nominal significance and same effect direction when adjusted for sex and storage time. Of those, only cathepsin D remained significant following further adjustment for traditional cardiovascular risk factors (beta, -0.08; 95% confidence interval, -0.16, -0.01; P = 0.033; change in ln-transformed EDV per 1-SD increase in protein level). No protein was significantly related to FMD.Conclusion: Using a discovery/validation approach in two samples, our results indicate an inverse association between plasma cathepsin D levels and endothelial-dependent vasodilation.
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| 50. |
- Lind, Lars, et al.
(författare)
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Relationship between endothelium-dependent vasodilation and fat distribution using the new "imiomics" image analysis technique
- 2019
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Ingår i: NMCD. Nutrition Metabolism and Cardiovascular Diseases. - : Elsevier BV. - 0939-4753 .- 1590-3729. ; 29:10, s. 1077-1086
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: We investigated how vasoreactivity in the brachial artery and the forearm resistance vessels were related to fat distribution and tissue volume, using both traditional imaging analysis and a new technique, called “Imiomics”, whereby vasoreactivity was related to each of the >2M 3D image elements included in the whole-body magnetic resonance imaging (MRI).Methods and results: In 326 subjects in the Prospective investigation of Obesity, Energy and Metabolism (POEM) study (all aged 50 years), endothelium-dependent vasodilation was measured by acetylcholine infusion in the brachial artery (EDV) and flow-mediated vasodilation (FMD). Fat distribution was evaluated by dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). EDV, but not FMD, was significantly related to total fat mass, liver fat, subcutaneous (SAT) and visceral (VAT) adipose tissue in a negative fashion in women, but not in men. Using Imiomics, an inverse relationship was seen between EDV and a local tissue volume of SAT in both the upper part of the body, as well as the gluteo-femoral part and the medial parts of the legs in women. Also the size of the liver, heart and VAT was inversely related to EDV. In men, less pronounced relationships were seen. FMD was also significantly related to local tissue volume of upper-body SAT and liver fat in women, but less so in men.Conclusion: EDV, and to a lesser degree also FMD, were related to liver fat, SAT and VAT in women, but less so in men. Imiomics both confirmed findings from traditional methods and resulted in new, more detailed results.
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