Orthostatic hypotension is associated with higher levels of circulating endostatin.

Aims: The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumour effects proposed to be involved in blood pressure (BP) regulation. Methods and results: We compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH. Endostatin levels were significantly higher in OH patients (59 024 ± 2513 pg/mL) vs. controls (44 090 ± 1978pg/mL, P < 0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing (P < 0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95% confidence interval 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors. Conclusion: Circulating endostatin is elevated in patients with OH and may serve as a potential clinical marker of increased cardiovascular risk in patients with OH. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms.

Plasma Metabolome Predicts Aortic Stiffness and Future Risk of Coronary Artery Disease and Mortality After 23 Years of Follow-Up in the General Population.

BACKGROUND: Increased aortic stiffness (arteriosclerosis) is associated with early vascular aging independent of age and sex. The underlying mechanisms of early vascular aging remain largely unexplored in the general population. We aimed to investigate the plasma metabolomic profile in aortic stiffness (vascular aging) and associated risk of incident cardiovascular disease and mortality. METHODS AND RESULTS: We included 6865 individuals from 2 Swedish population-based cohorts. Untargeted plasma metabolomics was performed by liquid-chromatography mass spectrometry. Aortic stiffness was assessed directly by carotid-femoral pulse wave velocity (PWV) and indirectly by augmentation index (AIx@75). A least absolute shrinkage and selection operator (LASSO) regression model was created on plasma metabolites in order to predict aortic stiffness. Associations between metabolite-predicted aortic stiffness and risk of new-onset cardiovascular disease, cardiovascular mortality, and all-cause mortality were calculated. Metabolite-predicted aortic stiffness (PWV and AIx@75) was positively associated particularly with acylcarnitines, dimethylguanidino valeric acid, glutamate, and cystine. The plasma metabolome predicted aortic stiffness (PWV and AIx@75) with good accuracy (R2=0.27 and R2=0.39, respectively). Metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly correlated with age, sex, systolic blood pressure, body mass index, and low-density lipoprotein. After 23 years of follow-up, metabolite-predicted aortic stiffness (PWV and AIx@75) was significantly associated with increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality. CONCLUSIONS: Aortic stiffness is associated particularly with altered metabolism of acylcarnitines, cystine, and dimethylguanidino valeric acid. These metabolic disturbances predict increased risk of new-onset coronary artery disease, cardiovascular mortality, and all-cause mortality after more than 23 years of follow-up in the general population.

The Development and Evaluation of an Animated Video for Pre- and Postoperative Instructions for Patients with Osteoarthritis-A Design Science Research Approach.

Osteoarthritis (OA) is a condition in the hip or knee joints that develops during a long period of time and sometimes needs hip or knee joint replacement surgery when pain gets too intense for the patient. This paper describes how an animated video for pre- and postoperative instructions for patients with osteoarthritis was designed. The design science research (DSR) approach was followed by creating a web-based animated video. The web-based animated video is used to support surgical departments with education for patients suffering from OA. In the web-based animated video, information about OA surgical treatment and its pre- and post-arrangements was included. The relevance, the rigor, and the design cycles were focused on, with some iterations of and improvements in the animations. Even after implementation, there was a feedback-loop with comments from the surgeons and their patients. Moreover, as more departments will use the web-based animated video, they want to make their special mark on it, so that further changes will be made. This paper presents the design and successful implementation of an animated video for pre- and postoperative instructions for patients with osteoarthritis, tightly linked to the patient journey and the workflow of healthcare professionals. The animated video serves not only as a tool to improve care but also as a basis for further scientific research studies.

Aortic Stiffness Can be Predicted From Different eGFR Formulas With Long Follow-Up in the Malmö Diet Cancer Study.

We studied the impact of estimated glomerular filtration rate (eGFR) based on either creatinine or cystatin C, or in combination, on vascular aging (aortic stiffness) and central hemodynamics (central systolic blood pressure) in a Swedish urban population with median 17 years of follow-up. Participants (n = 5049) from the population-based Malmö Diet and Cancer Study that underwent baseline examination and later participated in the prospective cardiovascular arm were selected. Of these, 2064 with measured carotid-femoral pulse wave velocity (cfPWV) and central blood pressure at follow-up were enrolled. eGFR was calculated using cystatin C (eGFRCYS) and creatinine (eGFRCR) equations: Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised (LMrev), and the European Kidney Function Consortium (EKFC) equations. Lower adjusted eGFRCR, but not eGFRCYS, were independently associated with higher cfPWV (P < .001, respectively). eGFR <60 mL/min/1.73 m2 determined higher cfPWV except when using the EKFC equation. Conversely, CAPA/LMrev and CAPA/EKFC ratios were not associated with aortic stiffness. Lower eGFRCR is associated with higher future aortic stiffness independently of age, sex, heart rate, mean blood pressure, body mass index, and antihypertensive treatment. The ratio of eGFRCYS and eGFRCR equations could not predict aortic stiffness at all.

Accumulation of advanced glycation end products in skin and increased vascular ageing in the general population: the Malmö Offspring Study.

OBJECTIVES: Advanced glycation end product (AGE) is an established risk marker for diabetic vascular disease, and associated with the degree of diabetes complications, renal failure, and atherosclerosis in middle-aged and older individuals. The relationship between AGEs and aortic stiffness has not been thoroughly examined in the younger general population. We aimed to evaluate the association between AGEs and aortic stiffness in the general population of young and middle-aged adults. METHODS: We analysed cross-sectionally 2518 participants from a Swedish population-based cohort, the Malmö Offspring Study (mean age 41.8 ±â€Š14.5 years, 52.2%). Advanced glycation end-products (AGEs) were measured by a well validated, noninvasive method using skin autofluorescence with AGE-Reader. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (PWV) and augmentation index (Aix) was calibrated to a standard heart rate of 75 bpm at the arteria radialis using SphygmoCor. Multivariable linear regression was performed stratified by age to analyse the association between skin AGE and aortic stiffness. RESULTS: Increased levels of AGEs were significantly associated with higher direct measurements of aortic stiffness (vascular ageing) in younger individuals (PWV ß 0.55 m/s, P  < 0.001) after adjustment for traditional cardiometabolic risk factors, however, not in older individuals (PWV ß 0.23 m/s, P  = 0.10). Indirect vascular ageing was also significantly associated with higher levels of AGEs in both younger (Aix ß 7.78, P  < 0.001) and older individuals (Aix ß 3.69, P  < 0.001). CONCLUSION: Higher levels of skin autofluorescence-AGEs are positively associated with increased vascular ageing in younger adults from the general population, independent of cardiometabolic risk factors.

Cardiovascular dysautonomia in postacute sequelae of SARS-CoV-2 infection.

Coronavirus disease 2019 (COVID-19) has led to a worldwide pandemic that continues to transform but will not go away. Cardiovascular dysautonomia in postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection has led to persistent symptoms in a large number of patients. Here, we define the condition and its associated symptoms as well as potential mechanisms responsible. We provide a careful and complete overview of the topic addressing novel studies and a generalized approach to the management of individuals with this complex and potentially debilitating problem. We also discuss future research directions and the important knowledge gaps to be addressed in ongoing and planned studies.

Pharmacological modulation of vascular ageing: A review from VascAgeNet.

Vascular ageing, characterized by structural and functional changes in blood vessels of which arterial stiffness and endothelial dysfunction are key components, is associated with increased risk of cardiovascular and other age-related diseases. As the global population continues to age, understanding the underlying mechanisms and developing effective therapeutic interventions to mitigate vascular ageing becomes crucial for improving cardiovascular health outcomes. Therefore, this review provides an overview of the current knowledge on pharmacological modulation of vascular ageing, highlighting key strategies and promising therapeutic targets. Several molecular pathways have been identified as central players in vascular ageing, including oxidative stress and inflammation, the renin-angiotensin-aldosterone system, cellular senescence, macroautophagy, extracellular matrix remodelling, calcification, and gasotransmitter-related signalling. Pharmacological and dietary interventions targeting these pathways have shown potential in ameliorating age-related vascular changes. Nevertheless, the development and application of drugs targeting vascular ageing is complicated by various inherent challenges and limitations, such as certain preclinical methodological considerations, interactions with exercise training and sex/gender-related differences, which should be taken into account. Overall, pharmacological modulation of endothelial dysfunction and arterial stiffness as hallmarks of vascular ageing, holds great promise for improving cardiovascular health in the ageing population. Nonetheless, further research is needed to fully elucidate the underlying mechanisms and optimize the efficacy and safety of these interventions for clinical translation.

Exploring cross-sectional and longitudinal symptomatic remission and subjective quality of life in schizophrenia.

Achieving symptomatic remission, as defined by the Remission in Schizophrenia Working Group, is intended to be a meaningful outcome for individuals with schizophrenia, resulting in enhanced well-being. Cross-sectional studies have reported an association between symptomatic remission and subjective quality of life (QoL). Longitudinal studies aimed at examining this association have showed mixed results. The aim of this study was to explore the relationship between symptomatic remission and subjective QoL, both cross-sectionally and longitudinally. The study comprised data from what were at most 386 patients with schizophrenia, of whom 122-140 were followed over a period of four years. Based on cross-sectional remission status and longitudinal remission pattern, differences in subjective QoL were explored. Remission status was assessed using the Positive and Negative Syndrome Scale (PANSS), and subjective QoL using the Short Form-36 Health Survey (SF-36). Both the cross-sectional and the longitudinal approach showed that patients in symptomatic remission had significantly higher subjective QoL. Patients who were in non-remission at baseline, but who achieved remission at follow-up, also had significantly higher subjective QoL at follow-up compared with baseline. The results from the study show a clear association between symptomatic remission and subjective QoL. However, achieving symptomatic remission does not appear to be a guarantee of sustained subjective QoL, and only continued stable remission appears to result in such an outcome.

Evidence for Impaired Renin Activity in Postural Orthostatic Tachycardia Syndrome.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a heterogeneous condition predominantly affecting autonomic control of the cardiovascular system. Its extensive symptom diversity implies multi-organ involvement that interacts in ways still requiring full exploration. Current understanding of POTS pathophysiology suggests alterations in the renin-angiotensin-aldosterone system as a possible contributing factor. Therefore, we investigated the relationship between the activity of the renin-angiotensin-aldosterone system and hemodynamic parameters in a cohort of POTS patients and controls recruited at a tertiary referral center. METHODS: The case-control study included 46 patients with POTS (27 ± 9 years), and 48 healthy controls (30 ± 9 years) without orthostatic intolerance. Plasma renin activity, expressed as angiotensin I generation, and plasma aldosterone were measured by enzyme-linked immunosorbent assay and were correlated with hemodynamic parameters obtained during active standing tests. RESULTS: Renin activity was significantly downregulated in POTS patients compared to healthy individuals (median, 3406 ng/mL vs. 9949 ng/mL, p < 0.001), whereas aldosterone concentration did not differ between POTS and healthy controls (median, 218 pmol/L vs. 218 pmol/L, p = 0.26). A significant inverse correlation between renin activity and supine and orthostatic blood pressure levels was observed in healthy individuals (p < 0.05 for all), but not in POTS patients. CONCLUSIONS: Renin activity, but not aldosterone concentration, is downregulated in patients with POTS. Moreover, renin activity in POTS is dissociated from supine and standing blood pressure levels in contrast to healthy individuals. These findings suggest impaired renin function in POTS, which may direct future therapeutic approaches.

Twenty-Four-Hour Ambulatory Blood Pressure Profile in Patients With Reflex Syncope and Matched Controls.

Background Ambulatory blood pressure (BP) monitoring has long been used to monitor BP in hypertension and lately emerged as a useful tool to detect hypotensive susceptibility in reflex syncope. However, hemodynamic characteristics in reflex syncope have not been sufficiently explored. The present study investigated the differences between ambulatory BP monitoring profiles associated with reflex syncope and normal population. Methods and Results This is an observational study comparing ambulatory BP monitoring data from 50 patients with reflex syncope and 100 controls without syncope, age- and sex-matched 1:2. Mean 24-hour systolic (SBP) and diastolic BP, pulse pressure (24-hour PP), dipping status, and number of daytime SBP drops <90 to 100 mm Hg were analyzed. Variables associated with reflex syncope were investigated using multivariable logistic regression. Patients with reflex syncope displayed significantly lower 24-hour SBP (112.9±12.6 versus 119.3±11.5 mm Hg, P=0.002), higher 24-hour diastolic BP (85.2±9.6 versus 79.1±10.6 mm Hg, P<0.001), and markedly lower 24-hour PP (27.7±7.6 versus 40.3±9.0 mm Hg, P<0.001) compared with controls. Daytime SBP drops <90 mm Hg were more prevalent in patients with syncope (44% versus 17%, P<0.001). Daytime SBP drops <90 mm Hg, 24-hour PP <32 mm Hg, 24-hour SBP ≤110 mm Hg, and 24-hour diastolic BP ≥82 mm Hg were independently associated with reflex syncope, with 24-hour PP <32 mm Hg achieving the highest sensitivity (80%) and specificity (86%). Conclusions Patients with reflex syncope have lower 24-hour SBP but higher 24-hour diastolic BP and more frequent daytime SBP drops <90 mm Hg than individuals without syncope. Our results support the presence of lower SBP and PP in reflex syncope and suggest a role for ambulatory BP monitoring in the diagnostic work-up of this condition.

Subclinical atherosclerosis and risk factors in relation to autonomic indices in the general population.

OBJECTIVE: Orthostatic hypotension and resting heart rate (RHR) are associated with cardiovascular disease (CVD). However, it is unknown how these factors relate to subclinical CVD. We examined the relationship between orthostatic blood pressure (BP) response, RHR and cardiovascular risk factors, including coronary artery calcification score (CACS) and arterial stiffness, in the general population. METHODS: We included 5493 individuals (age 50-64 years; 46.6% men) from The Swedish CArdioPulmonary-bio-Image Study (SCAPIS). Anthropometric and haemodynamic data, biochemistry, CACS and carotid-femoral pulse wave velocity (PWV) were retrieved. Individuals were categorized into binary variables that manifest orthostatic hypotension and in quartiles of orthostatic BP responses and RHR, respectively. Differences across the various characteristics were tested using χ 2 for categorical variables and analysis of variance and Kruskal-Wallis test for continuous variables. RESULTS: The mean (SD) SBP and DBP decrease upon standing was -3.8 (10.2) and -9.5 (6.4) mmHg, respectively. Manifest orthostatic hypotension (1.7% of the population) associated with age ( P  = 0.021), systolic, diastolic and pulse pressure ( P  < 0.001), CACS (<0.001), PWV ( P  = 0.004), HbA1c ( P  < 0.001) and glucose levels ( P  = 0.035). Age ( P  < 0.001), CACS ( P  = 0.045) and PWV ( P  < 0.001) differed according to systolic orthostatic BP, with the highest values seen in those with highest and lowest systolic orthostatic BP-responses. RHR was associated with PWV ( P  < 0.001), SBP and DBP ( P  < 0.001) as well as anthropometric parameters ( P  < 0.001) but not CACS ( P  = 0.137). CONCLUSION: Subclinical abnormalities in cardiovascular autonomic function, such as impaired and exaggerated orthostatic BP response and increased resting heart rate, are associated with markers of increased cardiovascular risk in the general population.

Orthostatic blood pressure adaptations, aortic stiffness, and central hemodynamics in the general population: insights from the Malmö Offspring Study (MOS).

PURPOSE: Arterial stiffness is independently associated with orthostatic hypotension in older individuals. The relationship between orthostatic blood pressure adaptation and aortic stiffness has not been thoroughly examined in a younger population. We investigated the relationship between orthostatic blood pressure adaptations, central aortic hemodynamics, and aortic stiffness in a cohort of predominantly younger and middle-aged adults. METHODS: We analyzed an observational, population-based study of 5259 individuals living in Malmö, Sweden. We related aortic stiffness and central hemodynamics assessed by carotid-femoral pulse wave velocity and pulse wave analysis at the arteria radialis using Sphygmocor to orthostatic blood pressure adaptation after 3 min standing. RESULTS: The mean age of the population was 41.9 ± 14.5 years, and 52.1% were women. We observed the highest aortic stiffness and central aortic blood pressure measurements in the lowest and highest quartiles of orthostatic systolic blood pressure differences (p < 0.001). Aortic stiffness and central aortic blood pressure gradually decreased across increasing quartiles of orthostatic diastolic blood pressure difference (p < 0.001). After full adjustment, orthostatic diastolic blood pressure remained significantly associated with aortic stiffness (p = 0.001) and central aortic blood pressure (p < 0.001), whereas orthostatic systolic blood pressure was significantly associated only with central aortic systolic blood pressure (p = 0.009). No significant associations were found between subclinical orthostatic hypotension, aortic stiffness, and central hemodynamics. CONCLUSIONS: Our findings demonstrate that altered blood pressure responses to orthostatic challenges, both blood pressure reductions and blood pressure increases, are independently and inversely associated with markers of aortic stiffness (vascular aging) in a predominantly young to middle-aged population.

Malmö POTS symptom score: Assessing symptom burden in postural orthostatic tachycardia syndrome.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a common cardiovascular autonomic disorder characterized by excessive heart rate (HR) increase on standing and symptoms of orthostatic intolerance, posing significant limitations on functional capacity. No objective tool exists to classify symptom burden in POTS. METHODS: We conducted a case-control study in 62 POTS patients and 50 healthy controls to compare symptom burden between groups using the newly developed, self-rating, 12-item, Malmö POTS Score (MAPS; 0-10 per item, total range 0-120) based on patients own perception of symptoms through visual analogue scale assessment. We have also explored correlations between symptom severity assessed by MAPS, basic clinical parameters and postural haemodynamic changes. RESULTS: POTS patients showed significantly higher total MAPS score (78 ± 20 vs. 14 ± 12, p < 0.001), higher baseline systolic blood pressure (BP), diastolic BP and HR (p < 0.001) compared with healthy controls. The most prominent symptoms in POTS were palpitations, fatigue and concentration difficulties. Haemodynamic parameters on standing were significantly correlated with palpitations in POTS after adjustment for age and sex (lower systolic and diastolic BP, and higher HR) (p < 0.001 for all). Orthostatic HR was significantly associated with concentration difficulties and total MAPS score. The optimal cut-point value of MAPS to differentiate POTS and healthy controls was ≥42 (sensitivity, 97%; specificity, 98%). CONCLUSIONS: Symptom severity, as assessed by MAPS score, is fivefold higher in POTS compared with healthy individuals. The new MAPS score can be useful as a semiquantitative system to assess symptom burden, monitor disease progression and evaluate pre-test likelihood of disease.

Plasma proteomic profiling in postural orthostatic tachycardia syndrome (POTS) reveals new disease pathways.

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder characterized by excessive heart rate increase on standing, leading to debilitating symptoms with limited therapeutic possibilities. Proteomics is a large-scale study of proteins that enables a systematic unbiased view on disease and health, allowing stratification of patients based on their protein background. The aim of the present study was to determine plasma protein biomarkers of POTS and to reveal proteomic pathways differentially regulated in POTS. We performed an age- and sex-matched, case-control study in 130 individuals (case-control ratio 1:1) including POTS and healthy controls. Mean age in POTS was 30 ± 9.8 years (84.6% women) versus controls 31 ± 9.8 years (80.0% women). We analyzed plasma proteins using data-independent acquisition (DIA) mass spectrometry. Pathway analysis of significantly differently expressed proteins was executed using a cutoff log2 fold change set to 1.2 and false discovery rate (p-value) of < 0.05. A total of 393 differential plasma proteins were identified. Label-free quantification of DIA-data identified 30 differentially expressed proteins in POTS compared with healthy controls. Pathway analysis identified the strongest network interactions particularly for proteins involved in thrombogenicity and enhanced platelet activity, but also inflammation, cardiac contractility and hypertrophy, and increased adrenergic activity. Our observations generated by the first use a label-free unbiased quantification reveal the proteomic footprint of POTS in terms of a hypercoagulable state, proinflammatory state, enhanced cardiac contractility and hypertrophy, skeletal muscle expression, and adrenergic activity. These findings support the hypothesis that POTS may be an autoimmune, inflammatory and hyperadrenergic disorder.

The Influence of Age on Cerebral Tissue Oxygenation in Vasovagal Syncope and Orthostatic Hypotension.

Age-related physiological impairment increases susceptibility to syncope. We tested the hypotheses that cerebral oxygenation during orthostatic provocation, as well as the level at which syncope occurs, differs according to age. Non-invasive hemodynamic monitoring and cerebral oximetry were applied during a head-up tilt test in 139 patients with vasovagal syncope (mean (SD) 45, (17) years, 60%-female); 121 patients with orthostatic hypotension (61.4 (19.2) years, 49.6%-female); and 82 patients with a negative head-up tilt test (45 (18) years, 61%-female). Group differences in cerebral tissue oxygenation levels and systolic blood pressure were assessed in supine at 3 and 10 min of orthostatic provocation, 30 s before (i.e., presyncopal phase) and during syncope in age groups of <30, 30−60, and >60 years. During the head-up tilt test, cerebral tissue oxygenation at the presyncopal phase decreased with age, both in patients with vasovagal syncope (<30 years: 66.9 ± 6.2, 30−60: 64.5 ± 6.1, >60: 62.2 ± 5.8%; p = 0.009) and orthostatic hypotension (<30: 67.4 ± 4.4, 30−60: 61.6 ± 6.2, >60: 57.5 ± 3.9; p < 0.001). Mean systolic blood pressure at the presyncopal phase did not differ according to age. Cerebral oxygenation prior to syncope in older individuals with vasovagal syncope and orthostatic hypotension is lower compared with younger individuals independently of systolic blood pressure. This suggests that the level of cerebral oxygenation at which syncope is elected is lower in older individuals.

Underlying hemodynamic differences are associated with responses to tilt testing.

Aim of this study was to explore whether differences in resting hemodynamic parameters may be associated with tilt test results in unexplained syncope. We analyzed age, gender, systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) by merging three large databases of patients considered likely to be of vasovagal reflex etiology, comparing patients who had tilt-induced reflex response with those who did not. Tilt-induced reflex response was defined as spontaneous symptom reproduction with characteristic hypotension and bradycardia. Relationship of demographics and baseline supine BP to tilt-test were assessed using logistic regression models. Individual records of 5236 patients (45% males; mean age: 60 ± 22 years; 32% prescribed antihypertensive therapy) were analyzed. Tilt-positive (n = 3129, 60%) vs tilt-negative patients had lower SBP (127.2 ± 17.9 vs 129.7 ± 18.0 mmHg, p < 0.001), DBP (76.2 ± 11.5 vs 77.7 ± 11.7 mmHg, p < 0.001) and HR (68.0 ± 11.5 vs 70.5 ± 12.5 bpm, p < 0.001). In multivariable analyses, tilt-test positivity was independently associated with younger age (Odds ratio (OR) per 10 years:1.04; 95% confidence interval (CI), 1.01-1.07, p = 0.014), SBP ≤ 128 mmHg (OR:1.27; 95%CI, 1.11-1.44, p < 0.001), HR ≤ 69 bpm (OR:1.32; 95%CI, 1.17-1.50, p < 0.001), and absence of hypertension (OR:1.58; 95%CI, 1.38-1.81, p < 0.001). In conclusion, among patients with suspected reflex syncope, younger age, lower blood pressure and lower heart rate are associated with positive tilt-test result.

Risk of incident fractures in individuals hospitalised due to unexplained syncope and orthostatic hypotension.

BACKGROUND: Impaired orthostatic blood pressure response and syncope confer a high risk of falls and trauma. The relationship between a history of unexplained syncope and orthostatic hypotension (OH) with subsequent fractures, however, has not been thoroughly examined. In this study, we aimed to investigate the relationship between previous hospital admissions due to unexplained syncope and OH and incident fractures in a middle-aged population. METHODS: We analysed a large population-based prospective cohort of 30,399 middle-aged individuals (age, 57.5 ± 7.6; women, 60.2%). We included individuals hospitalised due to unexplained syncope or OH as the main diagnosis. Multivariable-adjusted Cox regression analysis was applied to assess the impact of unexplained syncope and OH hospitalisations on subsequent incident fractures. RESULTS: During a follow-up period of 17.8 + 6.5 years, 8201 (27%) subjects suffered incident fractures. The mean time from baseline and first admission for syncope (n = 493) or OH (n = 406) was 12.6 ± 4.2 years, and the mean age of the first hospitalisation was 74.6 ± 7.4 years. Individuals with incident fractures were older, more likely to be women, and had lower BMI, higher prevalence of prevalent fractures, and family history of fractures. Multivariable-adjusted Cox regression showed an increased risk of incident fractures following hospitalisations due to unexplained syncope (HR 1.20; 95% CI 1.02-1.40; p = 0.025) and OH (HR 1.42; 95% CI 1.21-1.66; p < 0.001) compared with unaffected individuals. CONCLUSIONS: Individuals hospitalised due to unexplained syncope and orthostatic hypotension have an increased risk of subsequent fractures. Our findings suggest that such individuals should be clinically assessed for their syncope aetiology, with preventative measures aimed at fall and fracture risk assessment and management.

Circulating levels of growth hormone in postural orthostatic tachycardia syndrome.

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder with poorly understood etiology and underlying pathophysiology. Since cardiovascular morbidity has been linked to growth hormone (GH), we studied GH levels in patients with POTS. We conducted an age-sex-matched case-control study in patients with POTS (age 31 ± 9 years; n = 42) and healthy controls (32 ± 9 years; n = 46). Plasma GH levels were measured using high-sensitivity chemiluminescence sandwich immunoassay. The burden of orthostatic intolerance symptoms was assessed by the Orthostatic Hypotension Questionnaire (OHQ), consisting of a symptom assessment scale (OHSA) and a daily activity scale (OHDAS). POTS patients had significantly higher composite OHQ score than controls, more symptoms and less activity. Supine heart rate and diastolic blood pressure (BP), but not systolic BP, were significantly higher in POTS. Median plasma GH levels were significantly lower in POTS (0.53 ng/mL) than controls (2.33 ng/mL, p = 0.04). GH levels were inversely related to OHDAS in POTS and supine systolic BP in POTS and controls, but not heart rate neither group. POTS is associated with lower GH levels. Impairment of daily life activities is inversely related with GH in POTS. A higher supine diastolic BP is inversely associated with GH levels in POTS and healthy individuals.

Long-Haul Post-COVID-19 Symptoms Presenting as a Variant of Postural Orthostatic Tachycardia Syndrome: The Swedish Experience.

Major clinical centers in Sweden have witnessed an inflow of patients with chronic symptoms following initial outpatient care for coronavirus disease-2019 (COVID-19) infection, suggestive of postural orthostatic tachycardia syndrome. This report presents the first case series of 3 Swedish patients diagnosed with postural orthostatic tachycardia syndrome more than 3 months after the primary COVID-2019 infections. (Level of Difficulty: Intermediate.).