Trends in incidence, mortality, and causes of death associated with systemic sclerosis in Denmark between 1995 and 2015:a nationwide cohort study

Variables and sources. Diagnoses (ICD-8 and ICD-10) and medication (ATC, Anatomical Therapeutical Chemical) codes used. (DOCX 20 kb

Association of genetic variants previously implicated in coronary artery disease with age at onset of coronary artery disease requiring revascularizations

BACKGROUND:The relation between burden of risk factors, familial coronary artery disease (CAD), and known genetic variants underlying CAD and low-density lipoprotein cholesterol (LDL-C) levels is not well-explored in clinical samples. We aimed to investigate the association of these measures with age at onset of CAD requiring revascularizations in a clinical sample of patients undergoing first-time coronary angiography. METHODS:1599 individuals (mean age 64 years [min-max 29-96 years], 28% women) were genotyped (from blood drawn as part of usual clinical care) in the Copenhagen area (2010-2014). The burden of common genetic variants was measured as aggregated genetic risk scores (GRS) of single nucleotide polymorphisms (SNPs) discovered in genome-wide association studies. RESULTS:Self-reported familial CAD (prevalent in 41% of the sample) was associated with -3.2 years (95% confidence interval -4.5, -2.2, p<0.0001) earlier need of revascularization in sex-adjusted models. Patients with and without familial CAD had similar mean values of CAD-GRS (unweighted scores 68.4 vs. 68.0, p = 0.10, weighted scores 67.7 vs. 67.5, p = 0.49) and LDL-C-GRS (unweighted scores 58.5 vs. 58.3, p = 0.34, weighted scores 63.3 vs. 61.1, p = 0.41). The correlation between the CAD-GRS and LDL-C-GRS was low (r = 0.14, p<0.001). In multivariable adjusted regression models, each 1 standard deviation higher values of LDL-C-GRS and CAD-GRS were associated with -0.70 years (95% confidence interval -1.25, -0.14, p = 0.014) and -0.51 years (-1.07, 0.04, p = 0.07) earlier need for revascularization, respectively. CONCLUSIONS:Young individuals presenting with CAD requiring surgical interventions had a higher genetic burden of SNPs relating to LDL-C and CAD (although the latter was statistically non-significant), compared with older individuals. However, the absolute difference was modest, suggesting that genetic screening can currently not be used as an effective prediction tool of when in life a person will develop CAD. Whether undiscovered genetic variants can still explain a "missing heritability" in early-onset CAD warrants more research

Effect of Increased Potassium Intake on Adrenal Cortical and Cardiovascular Responses to Angiotensin II:A Randomized Crossover Study

BACKGROUND: Increased potassium intake lowers blood pressure in patients with hypertension, but increased potassium intake also elevates plasma concentrations of the blood pressure‐raising hormone aldosterone. Besides its well‐described renal effects, aldosterone is also believed to have vascular effects, acting through mineralocorticoid receptors present in endothelial and vascular smooth muscle cells, although mineralocorticoid receptors‐independent actions are also thought to be involved. METHODS AND RESULTS: To gain further insight into the effect of increased potassium intake and potassium‐stimulated hyperaldosteronism on the human cardiovascular system, we conducted a randomized placebo‐controlled double‐blind crossover study in 25 healthy normotensive men, where 4 weeks treatment with a potassium supplement (90 mmol/day) was compared with 4 weeks on placebo. At the end of each treatment period, we measured potassium and aldosterone in plasma and performed an angiotensin II (AngII) infusion experiment, during which we assessed the aldosterone response in plasma. Hemodynamics were also monitored during the AngII infusion using ECG, impedance cardiography, finger plethysmography (blood pressure‐monitoring), and Doppler ultrasound. The study showed that higher potassium intake increased plasma potassium (mean±SD, 4.3±0.2 versus 4.0±0.2 mmol/L; P=0.0002) and aldosterone (median [interquartile range], 440 [336–521] versus 237 [173–386] pmol/L; P<0.0001), and based on a linear mixed model for repeated measurements, increased potassium intake potentiated AngII‐stimulated aldosterone secretion (P=0.0020). In contrast, the hemodynamic responses (blood pressure, total peripheral resistance, cardiac output, and renal artery blood flow) to AngII were similar after potassium and placebo. CONCLUSIONS: Increased potassium intake potentiates AngII‐stimulated aldosterone secretion without affecting systemic cardiovascular hemodynamics in healthy normotensive men. REGISTRATION: EudraCT Number: 2013‐004460‐66; URL: https://www.ClinicalTrials.gov; Unique identifier: NCT02380157