Background: Multimorbidity, the co-occurrence of two or more diseases in one patient, is a frequent phenomenon. Understanding how different diseases condition each other over the lifetime of a patient could significantly contribute to personalised prevention efforts. However, most of our current knowledge on the long-term development of the health of patients (their disease trajectories) is either confined to narrow time spans or specific (sets of) diseases. Here, we aim to identify decisive events that potentially determine the future disease progression of patients. Methods: Health states of patients are described by algorithmically identified multimorbidity patterns (groups of included or excluded diseases) in a population-wide analysis of 9,000,000 patient histories of hospital diagnoses observed over 17 years. Over time, patients might acquire new diagnoses that change their health state; they describe a disease trajectory. We measure the age- and sex-specific risks for patients that they will acquire certain sets of diseases in the future depending on their current health state. Results: In the present analysis, the population is described by a set of 132 different multimorbidity patterns. For elderly patients, we find 3 groups of multimorbidity patterns associated with low (yearly in-hospital mortality of 0.2–0.3%), medium (0.3–1%) and high in-hospital mortality (2–11%). We identify combinations of diseases that significantly increase the risk to reach the high-mortality health states in later life. For instance, in men (women) aged 50–59 diagnosed with diabetes and hypertension, the risk for moving into the high-mortality region within 1 year is increased by the factor of 1.96 ± 0.11 (2.60 ± 0.18) compared with all patients of the same age and sex, respectively, and by the factor of 2.09 ± 0.12 (3.04 ± 0.18) if additionally diagnosed with metabolic disorders. Conclusions: Our approach can be used both to forecast future disease burdens, as well as to identify the critical events in the careers of patients which strongly determine their disease progression, therefore constituting targets for efficient prevention measures. We show that the risk for cardiovascular diseases increases significantly more in females than in males when diagnosed with diabetes, hypertension and metabolic disorders.

We aimed to investigate the effect of gender-affirming hormone therapy (GAHT) on cardiovascular disease risk factors focusing on glucose tolerance.This primarily translational study enrolled 16 tra...

Background: Although men are more prone to developing cardiovascular disease (CVD) than women, risk factors for CVD, such as nicotine abuse and diabetes mellitus, have been shown to be more detrimental in women than in men. Objective: We developed a method to systematically investigate population-wide electronic health records for all possible associations between risk factors for CVD and other diagnoses. The developed structured approach allows an exploratory and comprehensive screening of all possible comorbidities of CVD, which are more connected to CVD in either men or women. Methods: Based on a population-wide medical claims dataset comprising 44 million records of inpatient stays in Austria from 2003 to 2014, we determined comorbidities of acute myocardial infarction (AMI; International Classification of Diseases, Tenth Revision [ICD-10] code I21) and chronic ischemic heart disease (CHD; ICD-10 code I25) with a significantly different prevalence in men and women. We introduced a measure of sex difference as a measure of differences in logarithmic odds ratios (ORs) between male and female patients in units of pooled standard errors. Results: Except for lipid metabolism disorders (OR for females [ORf]=6.68, 95% confidence interval [CI]=6.57-6.79, OR for males [ORm]=8.31, 95% CI=8.21-8.41), all identified comorbidities were more likely to be associated with AMI and CHD in females than in males: nicotine dependence (ORf=6.16, 95% CI=5.96-6.36, ORm=4.43, 95% CI=4.35-4.5), diabetes mellitus (ORf=3.52, 95% CI=3.45-3.59, ORm=3.13, 95% CI=3.07-3.19), obesity (ORf=3.64, 95% CI=3.56-3.72, ORm=3.33, 95% CI=3.27-3.39), renal disorders (ORf=4.27, 95% CI=4.11-4.44, ORm=3.74, 95% CI=3.67-3.81), asthma (ORf=2.09, 95% CI=1.96-2.23, ORm=1.59, 95% CI=1.5-1.68), and COPD (ORf=2.09, 95% CI 1.96-2.23, ORm=1.59, 95% CI 1.5-1.68). Similar results could be observed for AMI. Conclusions: Although AMI and CHD are more prevalent in men, women appear to be more affected by certain comorbidities of AMI and CHD in their risk for developing CVD.

Secretagogin (SCGN) is a calcium binding protein related to insulin release in the pancreas. Although SCGN is not co-released with insulin, plasma concentrations have been found to be increased in type 2 diabetes mellitus patients. Until now, no study on SCGN levels in pregnancy or patients with gestational diabetes mellitus (GDM) has been published. In 93 women of a high-risk population for GDM at the Medical University of Vienna, secretagogin levels of 45 GDM patients were compared to 48 women with a normal glucose tolerance (NGT). Glucose tolerance, insulin resistance and secretion were assessed with oral glucose tolerance tests (OGTT) between the 10th and 28th week of gestation (GW) and postpartum. In all women, however, predominantly in women with NGT, there was a significant positive correlation between SCGN levels and Stumvoll first (r_p = 0.220, p = 0.032) and second phase index (r_p = 0.224, p = 0.028). SCGN levels were not significantly different in women with NGT and GDM. However, SCGN was higher postpartum than during pregnancy (postpartum: 88.07 ± 35.63 pg/mL; pregnancy: 75.24 ± 37.90 pg/mL, p = 0.004). SCGN was directly correlated with week of gestation (r_p = 0.308; p = 0.021) and triglycerides (r_p = 0.276; p = 0.038) in women with GDM. Therefore, SCGN is related to insulin secretion and hyperinsulinemia during pregnancy; however, it does not display differences between women with NGT and GDM.

Objective: Differences in cardiac parameters such as myocardial mass, left ventricular ejection fraction (LVEF), cardiac output, and brain natriuretic peptide (NT-proBNP) levels between cisgender men and women are well established. No evidence exists regarding changes in myocardial mass or cardiac function parameters in transgender individuals undergoing gender-affirming hormone therapy (GAHT). Design, setting, participants, and main outcomes: A prospective study enrolling transgender individuals under GAHT (20 individuals assigned female at birth [AFAB] and 15 assigned male at birth [AMAB]) was conducted at the Medical University of Vienna from 2019 to 2022. A 3-Tesla electrocardiogram-gated magnetic resonance imaging measured myocardial mass, LVEF, and other cardiac function parameters before GAHT and at 6-month follow-up. Myocardial lipid content was quantified using magnetic resonance spectroscopy. Results: In AFAB, myocardial mass increased significantly after 6 months of GAHT from mean (±SD) 48 (±8) g/m2 at baseline to 54 (±7) g/m2 at follow-up (P = .011). Individuals assigned male at birth showed a nonsignificant decrease of 4 (±14) g/m2 in myocardial mass. In both groups, no significant changes were noted in LVEF, stroke volume, cardiac output, or peak filling rate. Neither testosterone (AFAB: r = −0.127, P = .679; AMAB: r = −0.127, P = .679) nor estradiol levels (AFAB: r = −0.154, P = .616; AMAB: r = −0.154, P = .616) nor body mass index was related to myocardial mass at follow-up. Brain natriuretic peptide levels in AFAB were significantly reduced at follow-up (from median [IQR] 41 [26-57] to 19 [12-34] pg/mL). Conclusions: Myocardial mass increased, while NT-proBNP levels decreased significantly in AFAB after 6 months of GAHT. However, no significant changes in cardiac function were noted in AMAB and AFAB. Registration: ClinicalTrials.gov: NCT06245681 (registered 07 February 2024, https://classic.clinicaltrials.gov/ct2/show/NCT06245681).

Zusammenfassung: Schilddrüsenhormone steuern direkt und indirekt viele metabolische Vorgänge, welche für Wachstum, Entwicklung und Stoffwechsel entscheidend sind. Ein essenzieller Mikronährstoff für die Schilddrüsenhormonproduktion ist Jod, welches einen Bestandteil der Schilddrüsenhormone Triiodthyronin (T3) und Thyroxin (T4) bildet. Österreich ist aufgrund der geografischen Lage für Jodmangel prädisponiert. Jodmangel kann speziell in der Schwangerschaft und Stillzeit problematisch sein, weshalb in dieser Population eine Jodsupplementation empfohlen wird. Selen trägt in der Form der Aminosäure Selenocystein als Bestandteil von Dejodinasen einen maßgeblichen Teil zur Funktion der Schilddrüse, zum Beispiel bei der Umwandlung zwischen aktiven und inaktiven Formen von Schilddrüsenhormonen, bei. Die bisher vorhandenen klinischen Daten deuten insgesamt auf ein beachtliches Potenzial von Selensupplementation bei Hypothyreose oder Autoimmunerkrankungen der Schilddrüse hin. Für andere Vitamine und Mineralstoffe wie Zink, Magnesium, Eisen, Vitamin D und C ist die derzeitige Studienlage unzureichend, um eine Empfehlung auszusprechen. Zusammenfassend ist neben der bereits in Leitlinien empfohlenen Behandlung von Jodmangelzuständen auch eine gezielte Selensupplementation für bestimmte Patientenpopulationen möglicherweise sinnvoll.