| 551. |
- Neisius, Ulf, et al.
(författare)
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Association of central and peripheral pulse pressure with intermediate cardiovascular phenoytpes.
- 2012
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Ingår i: Journal of Hypertension. - 1473-5598. ; 30:1, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We assessed the relationship between pulse pressure and intermediate cardiovascular phenotypes in a middle-aged cohort with high prevalence of hypertension. BACKGROUND: It has been suggested that central pulse pressure (cPP) is a better predictor of cardiovascular outcome than peripheral pulse pressure (pPP), particularly in the elderly. Yet, it is unclear if cPP provides additional prognostic information to pPP in younger individuals. METHODS: In 535 individuals we assessed cPP and pPP as well as the intermediate cardiovascular phenotypes pulse wave velocity (PWV; SphygmoCor, Complior, PulsePen), carotid intima-media thickness (C-IMT; carotid ultrasound), left-ventricular mass index (LVMI; echocardiography) and urinary albumin : creatinine ratio (ACR). cPP was derived noninvasively from brachial blood pressure by pulse wave analysis (PWA; SphygmoCor) based on radial pulse wave tonometry and a validated transfer function. RESULTS: The cohort contained 331 hypertensive participants of whom 84% were treated. The average age was 46 ± 16 years. When compared to pPP, cPP had stronger associations with PWV (r = 0.471 vs. r = 0.372; P < 0.01), C-IMT (r = 0.426 vs. r = 0.235; P < 0.01) and LVMI (r = 0.385 vs. r = 0.189; P < 0.01), but equal association with ACR (r = 0.236 vs. r = 0.226; P = n.s.). In contrast, after adjustment for age, mean arterial pressure, heart rate and hypertension status there was no significant difference between cPP and pPP for prediction of PWV (adjusted R, 0.399 vs. 0.413; P = 0.066), C-IMT (adjusted R, 0.399 vs. 0.413; P = 0.487) and LVMI (adjusted R, 0.181 vs. 0.170; P = 0.094) in multivariate analysis. CONCLUSION: In our middle-aged cohort with high prevalence of hypertension cPP is more closely correlated with cardiovascular phenotypes than pPP. When adjusted for relevant cofactors, however, cPP does not provide additional information beyond pPP.
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| 552. |
- Nessler, Jadwiga, et al.
(författare)
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Serum biomarkers and clinical outcomes in heart failure patients treated de novo with carvedilol
- 2013
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Ingår i: Cardiology Journal. - 1898-018X. ; 20:2, s. 144-151
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of inflammatory and hemodynamic stress biomarkers in heart failure (HF) patients treated de novo with beta-blockers has been poorly studied. Methods: A total of 86 patients (age 56 +/- 9 years, 81 men) with left ventricular ejection fraction (LVEF) < 40% and previously not treated with beta-blockers were initiated on carvedilol. At baseline and 12 months later we performed echocardiography, cardiopulmonary exercise testing, and determined serum levels of B-type natriuretic peptide (BNP), endothelin-1 (ET-1), C-reactive protein (CRP), interleukin-6, and tumor necrosis factor alpha (TNF-alpha). Patients were followed up over a total period of 9 +/- 3 years from baseline. Results: Increased baseline CRP and its on-treatment decrease were associated with improvement of LVEF (est. coefficient per one SD: 1.6; 95% CI: -0.05,3.28; p = 0.056, and -1.80; -3.43, -0.18; p = 0.030, respectively) and diminishing of LV end-systolic volume index [mL/m(2)] (-6.83; -11.32; -2.34; p = 0.003, and 5.85; 1.23; -10.46; p = 0.014, respectively). Higher baseline ET-1 and on-treatment increase in TNF-alpha predicted frequent admissions (>1) for cardiac complications (odds ratio per one SD: 1.98; 95% CI: 1.09-3.59; p = 0.025, and 2.07, 1.12-3.84, p = 0.021, respectively) whereas higher baseline BNP was asociated with increased mortality (hazard ratio per one SD: 2.09, 95% CI: 1.26-3.45; p = 0.004). Conclusions: Serum biomarkers may have different roles in prediction of clinical outcomes among HF patients treated de novo with carvedilol. (Cardiol J 2013; 20, 2: 144-151)
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| 553. |
- Neumann, Johannes Tobias, et al.
(författare)
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Prognostic Value of Cardiovascular Biomarkers in the Population.
- 2024
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 331:22, s. 1898-1909
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Tidskriftsartikel (refereegranskat)abstract
- Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies.To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors.Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years.Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein.The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses.The analyses included 164054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people.Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.
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| 554. |
- Newton-Cheh, Christopher, et al.
(författare)
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Association of common variants in NPPA and NPPB with circulating natriuretic peptides and blood pressure
- 2009
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:3, s. 348-353
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Tidskriftsartikel (refereegranskat)abstract
- We examined the association of common variants at the NPPA-NPPB locus with circulating concentrations of the natriuretic peptides, which have blood pressure-lowering properties. We genotyped SNPs at the NPPA-NPPB locus in 14,743 individuals of European ancestry, and identified associations of plasma atrial natriuretic peptide with rs5068 (P = 8 x 10(-70)), rs198358 (P = 8 x 10(-30)) and rs632793 (P = 2 x 10(-10)), and of plasma B-type natriuretic peptide with rs5068 (P = 3 x 10(-12)), rs198358 (P = 1 x 10(-25)) and rs632793 (P = 2 x 10(-68)). In 29,717 individuals, the alleles of rs5068 and rs198358 that showed association with increased circulating natriuretic peptide concentrations were also found to be associated with lower systolic (P = 2 x 10(-6) and 6 x 10(-5), respectively) and diastolic blood pressure (P = 1 x 10(-6) and 5 x 10(-5)), as well as reduced odds of hypertension (OR = 0.85, 95% CI = 0.79-0.92, P = 4 x 10(-5); OR = 0.90, 95% CI = 0.85-0.95, P = 2 x 10(-4), respectively). Common genetic variants at the NPPA-NPPB locus found to be associated with circulating natriuretic peptide concentrations contribute to interindividual variation in blood pressure and hypertension.
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| 555. |
- Ngo, Debby, et al.
(författare)
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Proteomic profiling reveals novel biomarkers and pathways in yype 2 diabetes risk
- 2021
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Ingår i: JCI Insight. - : American Society for Clinical Investigation. - 2379-3708. ; 6:5
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Tidskriftsartikel (refereegranskat)abstract
- Recent advances in proteomic technologies have made high throughput profiling of low abundance proteins in large epidemiological cohorts increasingly feasible. We investigated whether aptamer-based proteomic profiling could identify biomarkers associated with future development of type 2 diabetes (T2DM) beyond known risk factors. We identified dozens of markers with highly significant associations with future T2DM across two large longitudinal cohorts (n=2,839) followed for up to 16 years. We leveraged proteomic, metabolomic, genetic and clinical data from humans to nominate one specific candidate to test for potential causal relationships in model systems. Our studies identified functional effects of aminoacylase 1 (ACY1), a top protein association with future T2DM risk, on amino acid metabolism and insulin homeostasis in vitro and in vivo. Further, a loss-of-function variant associated with circulating levels of the biomarker WAP, Kazal, immunoglobulin, Kunitz and NTR domain-containing protein 2 (WFIKKN2) was in turn associated with fasting glucose, hemoglobin A1c and HOMA-IR measurements in humans. In addition to identifying novel disease markers and potential pathways in T2DM, we provide publicly available data to be leveraged for new insights about gene function and disease pathogenesis in the context of human metabolism. .
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| 556. |
- Nikpay, Majid, et al.
(författare)
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A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease
- 2015
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:10, s. 1121-1121
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Tidskriftsartikel (refereegranskat)abstract
- Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association study (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of similar to 185,000 CAD cases and controls, interrogating 6.7 million common (minor allele frequency (MAF) > 0.05) and 2.7 million low-frequency (0.005 < MAF < 0.05) variants. In addition to confirming most known CAD-associated loci, we identified ten new loci (eight additive and two recessive) that contain candidate causal genes newly implicating biological processes in vessel walls. We observed intralocus allelic heterogeneity but little evidence of low-frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD, showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect size.
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| 557. |
- Nilsson, Christopher, et al.
(författare)
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Pro-Enkephalin and its association with renal function in Middle Eastern immigrants and native Swedes
- 2021
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Informa UK Limited. - 0036-5513 .- 1502-7686. ; 81:7, s. 573-578
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Tidskriftsartikel (refereegranskat)abstract
- Iraqi-born immigrants residing in Sweden exhibit lower blood pressure as well as better renal function despite an overall worse metabolic risk profile in comparison with native Swedes. This may indicate the presence of cardiorenal protective mechanisms in the Middle Eastern population. Hence, the aim of this study was to investigate whether the association between renal function and Pro-Enkephalin (PENK), a biomarker predictive of both acute and chronic kidney dysfunction, differs across ethnicities. The MEDIM population-based study including a cohort of women and men, born in Iraq or Sweden, aged 30–75 years was conducted in Malmö, Sweden, from 2010 to 2012. The study included fasting blood samples, physical examinations and self-administrated questionnaires. Despite significantly better renal function assessed by creatinine-based eGFR in the Iraqi group, levels of PENK did not differ between the groups, (70.0 pmol/L, born in Iraq (n = 1263) vs 71.1, born in Sweden (n = 689), p =.4). However, the association between PENK and renal function was relatively weaker in the Iraqi born group, as supported by a significant interaction between PENK and country of birth (P Interaction= Country of birth x PENK = 0,010). This observational study suggests that the association between renal function and PENK was weaker in Middle Eastern immigrants. This is of interest as PENK may exhibit a direct effect on renal function, however further research is needed including studies on causality.
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| 558. |
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| 559. |
- Nilsson, David, et al.
(författare)
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Spontaneous vs nitroglycerin-induced vasovagal reflex on head-up tilt : Are there neuroendocrine differences?
- 2016
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Ingår i: Heart Rhythm. - : Elsevier BV. - 1547-5271. ; 13:8, s. 1674-1678
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Tidskriftsartikel (refereegranskat)abstract
- Background Head-up tilt test (HUT) has been used for nearly 30 years for diagnosing vasovagal syncope (VVS) and was enhanced by sublingual nitroglycerin (glyceryl trinitrate [GTN]) challenge in the 1990s. Objective The purpose of this study was to explore neuroendocrine differences between spontaneous and drug-induced HUT positivity. Methods Two hundred eighty-eight patients (41.3% male, age 49 ± 21 years) with either positive passive (n = 60 [20.8%], age 38 ± 17 years) or GTN-enhanced HUT (n = 228, age 51 ± 21 years) were assessed. Beat-to-beat hemodynamic data, plasma epinephrine, plasma norepinephrine, plasma renin, C-terminal pro-arginine vasopressin (CT-proAVP), C-terminal endothelin-1, and mid-regional fragment of pro–atrial natriuretic peptide were measured resting supine and after 3 minutes of HUT. In multivariate–adjusted regression analyses controlling for age and gender, clinical, neuroendocrine, and hemodynamic parameters were compared between spontaneous and GTN-mediated positive tests. Results Patients with spontaneous VVS reported more syncope compared to those with GTN-mediated VVS (median interquartile range 6 [17] vs 4 [6], P = .002). There was no difference in resting concentrations of neurohormones between the 2 groups. However, after 3 minutes of HUT, those who later developed spontaneous VVS demonstrated higher levels of CT-proAVP (59.5 ± 137 vs 6.9 ± 4.6, P <0.001) and epinephrine (0.57 ± 1.43 vs 0.23 ± 0.19, P = .003), and lower blood pressure (119/73 vs 139/81 mm Hg, P <.001). Asystole during VVS was more common in the spontaneous VVS group (35% vs 17.5%, P = .016). Conclusion Patients with spontaneous VVS on HUT reported more syncopal events than those with drug-potentiated positive HUT, but both groups shared similar supine neuroendocrine profiles. However, spontaneous VVS during HUT is characterized by lower blood pressure, pronounced increases in epinephrine and vasopressin during early HUT phase, and higher frequency of reflex asystole.
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| 560. |
- Nilsson, Erik D., et al.
(författare)
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Copeptin, a Marker of Vasopressin, Predicts Vascular Dementia but not Alzheimer's Disease
- 2016
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Ingår i: Journal of Alzheimer's Disease. - : IOS Press. - 1387-2877 .- 1875-8908. ; 52:3, s. 1047-1053
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Copeptin is a reliable surrogate marker for the neurohypophyseal hormone vasopressin. Elevated plasma level of copeptin has been associated with cardiovascular and metabolic disease risk.OBJECTIVE: To investigate the association between copeptin and risk of dementia.METHODS: In all, 18,240 individuals from Malmö, Sweden, were examined between 2002 and 2006 (mean age 69.3 years, 69.8% men). Incident cases of dementia until 31 December 2009 were identified by linkage with the Swedish National Patient Register. To validate the dementia diagnoses, medical records as well as laboratory and neuroimaging data were carefully reviewed. Baseline level of copeptin was measured in frozen plasma in: (1) all participants who were diagnosed with dementia during follow-up, (2) a random sample of 5100 individuals of the cohort.RESULTS: During a median follow-up of 4.2 years, there were 374 incident dementia cases (age range 60-83 years at baseline): 120 were classified as Alzheimer's disease (AD), 84 as vascular dementia (VaD), and 102 as mixed dementia. In logistic regressions adjusted for cardiovascular risk factors, baseline level of copeptin predicted incident VaD (Odds ratio (OR) 1.30 per 1 SD increase in log copeptin, 95% CI 1.03-1.64). Copeptin did not predict incidence of all-cause dementia (OR 1.05, 95% CI 0.94-1.18), AD (OR 0.97, 95% CI 0.79-1.18), or mixed dementia (OR 0.85, 95% CI 0.68-1.05).CONCLUSION: Elevated plasma level of copeptin is a risk marker for incident VaD, but not for incident AD. This suggests that the vasopressin hormonal system might be involved in the development of VaD.
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