High-risk multimorbidity patterns on the road to cardiovascular mortality

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

Betatrophin is downregulated in pregnant women with a history of RYGB operation and a high risk of postprandial hypoglycaemia

Betatrophin is a liver and adipose tissue-derived protein which has recently been linked to glucose metabolism. So far, no data exist about the role of betatrophin in pregnant women with a history of Roux-En-Y gastric bypass (RYGB) operation with a high risk of postprandial hypoglycaemia. In this prospective clinical study, an oral glucose tolerance test (OGTT) and an intravenous glucose tolerance test (IVGTT) were performed between the 24th and 28th week of pregnancy and 3-6 months post-partum in a cohort of obese and normal-weight pregnant women, as well as in women with a history of RYGB operation. In the cohort of pregnant women with RYGB and exaggerated risk of postprandial hypoglycaemic events, basal and dynamic betatrophin levels during the OGTT were lower than in the obese or normal-weight pregnant women (basal levels: 13.66 ± 5.88 vs. 19.03 ± 4.15 vs. 15.68 ± 6.48, p = 0.016; OGTT 60': 13.33 ± 5.40 vs. 17.37 ± 3.16 vs. 15.84 ± 4.99, p = 0.030). During the OGTT, basal and dynamic betatrophin levels at 60' were positively associated with glucose levels at 60 min (r = 0.55, p = 0.01 and r = 0.45, p = 0.039). This positive association was followed by significant hypoglycaemic events in the RYGB group. It was only in the RYGB group that betatrophin was negatively related to the disposition index (rho = -0.53, p = 0.014). After pregnancy there was a decrease in basal and stimulated betatrophin levels during the OGTT in all three patient groups. In comparison to normal-weight and obese pregnant women, women with a history of RYGB operation and a high risk of postprandial hypoglycaemic events have lower levels of betatrophin. This indicate a mechanistic role in order to decrease the risk of postprandial hypoglycaemia in this specific cohort

Diagnosis of osteoporosis in statin-treated patients is dose-dependent

Objective Whether HMG-CoA-reductase inhibition, the main mechanism of statins, plays a role in the pathogenesis of osteoporosis, is not entirely known so far. Consequently, this study was set out to investigate the relationship of different kinds and dosages of statins with osteoporosis, hypothesising that the inhibition of the synthesis of cholesterol could influence sex-hormones and therefore the diagnosis of osteoporosis. Methods Medical claims data of all Austrians from 2006 to 2007 was used to identify all patients treated with statins to compute their daily defined dose averages of six different types of statins. We applied multiple logistic regression to analyse the dose-dependent risks of being diagnosed with osteoporosis for each statin individually. Results In the general study population, statin treatment was associated with an overrepresentation of diagnosed osteoporosis compared with controls (OR: 3.62, 95% CI 3.55 to 3.69, p<0.01). There was a highly non-trivial dependence of statin dosage with the ORs of osteoporosis. Osteoporosis was underrepresented in low-dose statin treatment (0–10 mg per day), including lovastatin (OR: 0.39, CI 0.18 to 0.84, p<0.05), pravastatin (OR: 0.68, 95% CI 0.52 to 0.89, p<0.01), simvastatin (OR: 0.70, 95% CI 0.56 to 0.86, p<0.01) and rosuvastatin (OR: 0.69, 95% CI 0.55 to 0.87, p<0.01). However, the exceeding of the 40 mg threshold for simvastatin (OR: 1.64, 95% CI 1.31 to 2.07, p<0.01), and the exceeding of a 20 mg threshold for atorvastatin (OR: 1.78, 95% CI 1.41 to 2.23, p<0.01) and for rosuvastatin (OR: 2.04, 95% CI 1.31 to 3.18, p<0.01) was related to an overrepresentation of osteoporosis. Conclusion Our results show that the diagnosis of osteoporosis in statin-treated patients is dose-dependent. Thus, osteoporosis is underrepresented in low-dose and overrepresented in high-dose statin treatment, demonstrating the importance of future studies’ taking dose-dependency into account when investigating the relationship between statins and osteoporosis

Sex, Gender, and Cardiovascular Health in Canadian and Austrian Populations

Background: Evidence differentiating the effect of biological sex from psychosociocultural factors (gender) in different societies and its relation to cardiovascular diseases is scarce. We explored the association between sex, gender, and cardiovascular health (CVH) among Canadian (CAN) and Austrian (AT) populations. Methods: The Canadian Community Health Survey (CCHS) (n = 63,522; 55% female) and Austrian Health Interview Survey (AT-HIS) (n = 15,771; 56% female) were analyzed in a cross-sectional survey design. The CANHEART/ATHEART index, a measure of ideal CVH composed of 6 cardiometabolic risk factors (smoking, physical activity, fruit and vegetable consumption, overweight/obesity, diabetes, and hypertension; range 0-6; higher scores reflecting better CVH) was calculated for both databases. A composite measure of psychosociocultural gender was computed for each country (range 0-1, higher score identifying characteristics traditionally ascribed to women). Results: Median CANHEART 4 (interquartile range 3-5) and CAN gender scores 0.55 (0.49-0.60) were similar to median ATHEART 4 (3-5) and AT gender scores 0.55 (0.46-0.64). Although higher gender scores (CCHS: β = −1.33, 95% confidence interval [CI] −1.44 to −1.22; AT-HIS: β = −1.08, 95% CI −1.26 to −0.89)) were associated with worse CVH, female sex (CCHS: β = 0.35, 95% CI (0.33-0.37); AT-HIS: β = 0.60, 95% CI (0.55-0.64)) was associated with better CVH in both populations. In addition, higher gender scores were associated with increased prevalence of heart disease compared with female sex. The magnitude of this risk was higher in Austrians. Conclusions: These results demonstrate that individuals with characteristics typically ascribed to women reported poorer cardiovascular health and higher risk of heart disease, independently from biological sex and baseline CV risk factors, in both countries. Female sex exhibited better CV health and a lower prevalence of heart disease than male in both populations. However, gender factors and magnitude of gender impact varied by country