Osteoporosis in children and young adults

Osteoporosis is a major public health problem with serious long-term complications. In children, the definition of osteoporosis is not only based on densitometric criteria but also takes into account vertebral and long bone fragility fractures. Several factors, such as long-term high-dose steroids, chronic inflammation, malnutrition, immobility, lack of sex steroids, and medication can reduce bone density and increase the risk for fragility fractures when left untreated. Also, genetic conditions can predispose to primary bone fragility disorders, with osteogenesis imperfecta being the most common. Furthermore, since the growing skeleton is at an increased rate of bone remodeling, the ability to heal long bone fractures and reshape vertebral fractures differentiates children from adults. The scope of this chapter is to review the risk factors of osteoporosis and fragility fractures and describe the commonest causes of primary and secondary osteoporosis and their management in children and young adults.     

Modifiable risk factors for bone health & fragility fractures

Osteoporosis is an ageing disorder characterised by poor microstructural architecture of the bone and an increase in the risk of fragility fractures, which often leads to hospitalisation and eventually a loss of mobility and independence. By 2050, it is estimated that more than 30 million people in Europe will be affected by bone diseases, and European hospitalisation alone can approximately cost up to 3.5 billion euros each year [1]. Although inherited variation in bone mineral density (BMD) is pre-determined by up to 85% [2], there is a window of opportunity to optimise BMD and reduce fracture risk through key modifiable lifestyle factors during the life course. An optimal diet rich in micronutrients, such as calcium, vitamin D, and potassium, has long been considered an important modifiable component of bone health, which is attributed to their direct roles within bone metabolism. Recently, there has been emerging evidence to suggest that protein and even an adequate intake of fruit and vegetables may also play an important role in improving BMD [3,4]. Maintaining a physically active lifestyle is not only protective from non-communicable diseases such as cardiovascular disease but it also has been shown to lessen the risk of fractures later in life, thereby making it an imperative modifiable factor for bone health, particularly as it also supports peak bone mass attainment during childhood/adolescence and can facilitate the maintenance of bone mass throughout adulthood [5]. Other key lifestyle factors that could be potentially modified to reduce the risk of osteoporosis or osteoporotic fractures later in life include smoking status, alcohol intake, and body composition [6]. Therefore, the principle aim of this review is to highlight the recent evidence pertaining to modifiable lifestyle factors that contribute to optimal bone health and the prevention of fragility fractures in later life.     

Bone health assessment in clinical practice is infrequenty performed in patients with chronic pancreatitis

BackgroundChronic pancreatitis (CP) patients have a high prevalence of osteoporotic fractures. In addition to prevalence of osteoporotic fractures, we evaluated how often bone health is assessed by dual-energy x-ray absorptiometry (DXA) in clinical practice, and the performance of Fracture Risk Assessment Tool (FRAX®) in predicting fracture risk in CP patients.MethodsMedical records of CP patients age ≥40 years prospectively enrolled in the North American Pancreatitis Study 2 (NAPS2) from the University of Pittsburgh Medical Center from 2000 to 2014 were retrospectively reviewed to gather additional relevant data before, at, and after enrollment until December 2016. We determined if patients underwent DXA, compared their observed prevalence of fractures with published data from two large US studies based on administrative data, and their predicted fracture risk with US population based on FRAX®.ResultsOnly 21% (49/239) patients were evaluated by DXA during their care. The observed cumulative prevalence of fragility fractures in NAPS2 CP patients (9.2%, 95% confidence interval 5.9–13.6) was significantly greater than in controls (1.46% and 2.16%, p ≤ 0.001 for each comparison) and CP patients (4.66%, and 5.13%, p < 0.005 for each comparison) in the two US administrative data studies. The FRAX® 10-year probability of major osteoporotic fracture of ≥20% (5.1% vs. 8.3%, p > 0.05) and for hip fracture of ≥3% (19.6% vs. 18.9%, p > 0.05) in NAPS2 CP patients did not differ from the US population.ConclusionsDespite their high risk of fragility fractures, bone health is infrequently assessed in CP patients. FRAX® may not adequately predict fracture risk in CP patients.     

Differences in Demographics and Outcomes Between Men and Women With Spontaneous Coronary Artery Dissection

BackgroundSpontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of myocardial infarction (MI) that most frequently affects women. The characteristics of men with SCAD are less well described.ObjectivesThe aim of this study was to describe the characteristics of men with SCAD.MethodsWe compared baseline demographics, clinical presentation, angiographic findings and cardiovascular outcomes of men and women in the Canadian SCAD Study. Major adverse cardiovascular events (MACE) were composite of death, MI, stroke or transient ischemic attack, heart failure hospitalization, and revascularization.ResultsOf 1,173 patients with SCAD, 123 (10.5%) were men. Men with SCAD were younger than women (mean age 49.4 ± 9.6 years vs 52.0 ± 10.6 years; P = 0.01). Men had lower rate of prior MI than women (0.8% vs 7.0%; P = 0.005). Men were less likely to have fibromuscular dysplasia (FMD) (27.8% vs 52.7%; P = 0.001), depression (9.8% vs 20.2%; P = 0.005), emotional stress (35.0% vs 59.3%; P < 0.001), or high score on the Perceived Stress Scale (3.5% vs 11.0%; P = 0.025) but were more likely to report isometric physical stress (40.2% vs 24.0%; P = 0.007). There was no difference in angiographic types of SCAD, but men had more circumflex artery (44.4% vs 30.9%; P = 0.001) and fewer right coronary artery (11.8% vs 21.7%; P = 0.0054) dissections. At median follow-up of 3.0 (IQR: 2.0-3.8) years, men had fewer hospital presentations with chest pain (10.6% vs 24.8%; P < 0.001). There were no differences in in-hospital events or follow-up MACE (7.3% vs 12.7%; P = 0.106).ConclusionsTen percent of SCAD patients were men. Men were younger and more likely to have a physical trigger but were less likely to have FMD, depression, or an emotional trigger. Men had less recurrent chest pain but no significant difference in MACE.     

Associations of visit-to-visit fasting glucose with risk of mortality: A retrospective cohort study of 48,077 people with type 2 diabetes

AimTo investigate the association between mean fasting glucose (FG) and variability in visit-to-visit FG and risk of mortality in people with type 2 diabetes (T2D).MethodsThis retrospective cohort study included 48,077 Chinese men and women with T2D. The yearly mean and coefficient of variation for fasting glucose (mean-FG and FG-CV, respectively) were based on at least two measurements taken each year over a mean duration of 4.5 years. Deaths and their causes were identified using the Shanghai Vital Statistics registry. Mean-FG and FG-CV served as time-dependent variables in Cox models to estimate their associations with risk of mortality; hazard ratios (HRs) were adjusted for baseline risk factors. Potential non-linear associations were examined by restricted cubic splines.ResultsDuring an average 4.5 years of follow-up, 2095 men and 1923 women died. Men with low mean-FG and women with low or high FG were at greater risk of death. Mean-FG was not associated with either cardiovascular disease (CVD) or cancer-specific mortality, whereas higher yearly FG-CV was associated with all-cause and CVD-/cancer-specific mortality in both genders. Compared with a yearly FG-CV of 1.76 (5th percentile), men and women with an FG-CV of 14.14 (75th percentile) had HRs (95% CI) of 1.41 (1.24–1.61) and 1.44 (1.26–1.65), respectively, for all-cause mortality.ConclusionVariability of visit-to-visit FG may be a more sensitive predictor of risk of death than mean-FG in people with T2D.     

Prevalence and predictive factors of undernutrition and low bone mineral density in children with chronic pancreatitis

BackgroundMalnutrition and bone disease are common in adults with chronic pancreatitis (CP). We studied the nutritional status and bone mineral density (BMD) of children with CP and the factors predicting them.MethodsCP children were prospectively evaluated with a detailed questionnaire, anthropometry, 25-hydroxy vitamin D, fecal elastase and BMD [total body less head (TBLH), spine and hip] by dual energy x-ray absorptiometry. Body mass index (BMI) Z score of ?1 to ?1.9, ?2 to ?2.9 and <-3 was taken as mild, moderate and severe malnutrition respectively. Low BMD and osteoporosis were defined as per International Society for Clinical Densitometry.Results83 children (46 boys, 14[4.3–21]years) with CP were enrolled. Majority had Cambridge IV (51,62.2%) or III (15,18.3%) changes. 34(41%) had undernutrition (mild-37.3%, moderate-2.4%, severe-1.2%). Overweight and obesity were present in 3.6% and 1.2% cases. BMI had a significant correlation with haemoglobin, serum albumin, percentage body fat and BMD. A majority had low fecal elastase (69 [84.1%], <100 μg/g) and vitamin D deficiency (70[84.3%],<20 ng/ml). 9 cases had a history of fractures. 14/75(18.6%) cases had low TBLH-BMD and this group had a lower BMI (?1.3[-1.9 to 0.34] vs 0.8 [-2.1 to 5.50; p = 0.03) than patients with normal BMD. There was no difference in age, disease duration, vitamin D, fecal elastase and Cambridge grade between normal and low BMD.Conclusions41% CP children have undernutrition with a majority having mild undernutrition. Nearly 20% have low BMD, with osteoporosis in none. Subjects with low BMI have lower BMD and percentage body fat.     

Sex-specific association of BMI change with stroke in middle-aged and older adults with type 2 diabetes

Background and aimsWe aimed to evaluate the association between BMI change and stroke in middle-aged and older adults with type 2 diabetes and identify sex differences.Methods and resultsThe China Health and Retirement Longitudinal Study is an ongoing national population-based cohort study. Participants aged 45 or above with type 2 diabetes were enrolled and followed for stroke incidence. BMI change was defined as BMI at 2013-BMI at 2011. Of 1774 participants (mean [SD] age in 2011, 60.23 [8.88] years), 795 (44.8 %) were men. A total of 112 incident stroke cases were confirmed up to 2018. The incidence rate of stroke was similar between men and women (6.79 % vs 5.92 %, P = 0.516). BMI increase was independently associated with an increased stroke risk (adjusted odds ratio, 1.15; 95 % CI, 1.05–1.31) in men, while this positive association was not significant in women (adjusted odds ratio, 1.12; 95 % CI, 0.98–1.29). In addition, the positive dose–response relationship between BMI increase and stroke was observed only in men.ConclusionAmong middle-aged and older adults with type 2 diabetes, there is a sex-specific association of BMI change with stroke. An increase in BMI could result in a higher risk of incident stroke in men.     

Sex-Related Clinical Characteristics and Outcomes of Patients Undergoing Transcatheter Edge-to-Edge Repair for Secondary Mitral Regurgitation

ObjectivesThe authors sought to assess sex-based differences in characteristics and outcomes of patients undergoing transcatheter edge-to-edge mitral valve repair (TMVR) for secondary mitral regurgitation (SMR).BackgroundSubgroup analysis from the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) trial indicated potential sex-related differences in outcomes after TMVR. The impact of sex on results after TMVR in a real-world setting is unknown.MethodsThe authors assessed clinical outcomes and echocardiographic parameters in women and men undergoing TMVR for SMR between 2008 and 2018 who were included in the large, international, multicenter real-world EuroSMR registry (European Registry of Transcatheter Repair for Secondary Mitral Regurgitation).ResultsA total of 1,233 patients, including 445 women (36%) and 788 men (64%), were analyzed. Although women were significantly older and had fewer comorbidities than men, TMVR was equally effective in women and men (mitral regurgitation [MR] grade ≤2+ at discharge: 93.2% vs. 94.6% for women vs. men; p = 0.35). All-cause mortality at 1 year (17.9% vs. 18.9%, adjusted hazard ratio: 0.806; p = 0.46) and at 2-year follow-up (26.5% vs. 26.4%, adjusted hazard ratio: 0.757; p = 0.26) were similar in women versus men after multivariate regression analysis. Durability of MR reduction, improvement in symptoms, quality of life, and functional capacity did also not differ during follow-up.ConclusionsResults from the EuroSMR registry confirmed effective and similar MR reduction with TMVR in women and men. There were no sex-related differences in clinical outcomes up to 2 years of follow-up.     

Sex Differences in LV Remodeling and Hemodynamics in Aortic Stenosis: Sex-Specific Criteria for Severe Stenosis?

BackgroundThe current criteria for aortic stenosis (AS) severity have not incorporated sex-related differences.ObjectivesThe authors investigated sex-related serial changes in left ventricular (LV) structure/function and hemodynamics in AS.MethodsSerial echocardiograms of patients with severe AS (time 0; aortic valve area [AVA] ≤1 cm²) and ≥1 previous echocardiogram were compared between sexes.ResultsOf 927 patients (time 0: AVA 0.87 ± 0.11 cm², peak velocity 4.03 ± 0.65 m/s, mean Doppler systolic pressure gradient [MG] 40.6 ± 13.1 mm Hg), 393 (42%) were women. Women had smaller body surface area (BSA) (1.77 ± 0.22 m² vs 2.03 ± 0.20 m²; P < 0.001), lower stroke volume (SV) (81.1 ± 17.2 mL vs 88.3 ± 18.6 mL; P < 0.001), and more frequent low-gradient severe AS (n = 196 [50%] vs n = 181 [34%]; P < 0.001). Women consistently had smaller AVA, indexed AVA (AVAi), peak velocity, and MG than men. The difference in aortic valve gradient lessened when AVAi ≤0.6 cm²/m² was applied as severe AS (n = 694, women 43%, AVA 0.95 ± 0.17 cm², AVAi 0.50 ± 0.07 cm²/m²). Peak velocity (3.83 ± 0.66 m/s) and MG (36.5 ± 13.2 mm Hg) were lower based on AVAi severity criteria compared to those based on AVA. Men had a lower left ventricular ejection fraction (LVEF) (55.8% ± 14.8% vs 61.1% ± 11.7%; P < 0.001) and greater reduction in SV (?13.3 ± 19.6 mL vs ?7.4 ± 16.4 mL; P < 0.001) as AS progressed from moderate to severe. Concentric LV hypertrophy was more common and E/e? higher in women (21.2 ± 10.9 vs 18.8 ± 9.1; P < 0.001). SV, LVEF, AVA, peak velocity, and MG became precipitously worse when AVA reached 1.2 cm² in both sexes.ConclusionsSmaller BSA in women yields lower SV, resulting in lower aortic valve gradient than men. Indexed parameters by BSA are thus important in sex-related differences of aortic valve hemodynamics, but AVAi ≤0.6 cm²/m² includes individuals with moderate AS. Elevated filling pressure is more common in women. Men experience a larger reduction in SV and LVEF as AS progresses. The definition of AS severity may require different criteria between sexes.     

Neck circumference for predicting the occurrence of future cardiovascular events: A 7.6-year longitudinal study

Background & aimsThis study aimed to investigate whether neck circumference (NC) could be used to predict future cardiovascular (CV) events in a community-based Chinese cohort.Methods and resultsWe enrolled 1435 participants aged 50–80 years (men, 43.62%) from communities in Shanghai. High NC was defined as NC ≥ 38.5 cm in men and NC ≥ 34.5 cm in women. Kaplan-Meier analysis and Cox proportional hazards regression were performed to explore the association between NC and CV events. During a mean follow-up period of 7.6 years, 148 CV events (10.31%) occurred. The incidence of CV events was higher in men than in women (83 (13.26%) vs. 65 (8.03%), P = 0.002). Multivariable-adjusted Cox regression analysis showed that for every 1-SD increase in NC in the whole population, the hazard ratio (HR) of CV events was 1.45 (95% confidence interval [CI], 1.15–1.83). The dose-response association between NC and CV events was significant in men (HR, 1.37, 95% CI, 1.10–1.71) but not in women (HR, 1.19, 95% CI, 0.94–1.52). In comparison with participants showing low baseline NC, those with high baseline NC showed a significantly higher risk of CV events (HR, 1.59, 95% CI, 1.14–2.22). Further stratified by sex, the positive association remained significant in men (HR, 1.90, 95% CI, 1.21–2.98) but not in women (HR, 1.25, 95% CI, 0.75–2.07).ConclusionNC was significantly associated with the risk of future CV events in middle-aged and elderly populations in the community and was a better predictor in men.     

Dose–response relationship between distinct serum uric acid trajectories and metabolic syndrome risk: A 5-year prospective cohort study

Background and aimsAlthough high serum uric acid (SUA) at baseline has been linked to increased risk for metabolic syndrome (MetS), the association of longitudinal SUA changes with MetS risk is unclear. We aimed to examine the effect of distinct SUA trajectories on new-onset MetS risk by sex in a Chinese cohort.Methods and resultsA total of 2364 women and 2770 men who were free of MetS in 2013 were enrolled in this study and followed up to 2018. Group-based trajectory modeling was applied to identify SUA trajectories. Cox proportional hazards model was used to evaluate the association between SUA trajectory and new-onset MetS. The dose–response relationship between SUA trajectories and MetS risk was examined by treating trajectory groups as a continuous variable. During a median follow-up of 48.0 months, 311 (13.16%) women and 950 (34.30%) men developed MetS. SUA trajectories (2013–2018) were defined as four distinct patterns in both women and men: “low”, “moderate”, “moderate-high”, and “high”. Compared with “low” SUA trajectory, the adjusted hazard ratio for incident MetS among participants with “moderate”, “moderate-high” and “high” trajectory was in a dose–response manner: 1.75 (95% CI: 1.08–2.82), 1.94 (95% CI: 1.20–3.14), and 3.05 (95% CI: 1.81–5.13), respectively, for women; 1.20 (95% CI: 0.97–1.49), 1.48 (95% CI: 1.19–1.85), and 1.66 (95% CI: 1.25–2.21), respectively, for men.ConclusionsElevated SUA trajectories are associated with increased risk for new-onset MetS in women and men. Monitoring SUA trajectories may assist in identifying subpopulations at higher risk for MetS.     

Lifestyle factors associated with the transition from healthy to unhealthy adiposity among black South African adults over 10 years

Background and aimsObesity is associated with an increasing prevalence of cardiovascular diseases in Africa, but some obese individuals maintain cardiometabolic health. The aims were to track metabolically healthy overweight or obesity (MHO) over 10 years in African adults and to identify factors associated with a transition to metabolically unhealthy overweight or obesity (MUO).Methods and resultsThe participants were the South African cohort of the international Prospective Urban and Rural Epidemiological study. From the baseline data of 1937 adults, 649 women and 274 men were followed for 10 years. The combined overweight and obesity prevalence of men (19.2%–23.8%, p = .02) and women (58%–64.7%, p < .001), and the prevalence of the metabolic syndrome in all participants (25.4%–40.2%, p < .001) increased significantly. More than a quarter (26.2%) of the women and 10.9% of men were MHO at baseline, 11.4% of women and 5.1% of men maintained MHO over 10 years, while similar proportions (12.3% of women, 4.7% of men) transitioned to MUO. Female sex, age, and total fat intake were positively associated with a transition to MUO over 10 years, while physical activity was negatively associated with the transition. HIV positive participants were more likely to be MHO at follow-up than their HIV negative counterparts.ConclusionsOne in two black adults with BMI ≥25 kg/m² maintained MHO over 10 years, while a similar proportion transitioned into MUO. Interventions should focus on lower fat intakes and higher physical activity to prevent the transition to MUO.     

Association of Sex,Reduced Myocardial Flow Reserve,and Long-Term Mortality Across Spectrum of Atherosclerotic Disease

BackgroundCoronary vasomotor dysfunction (defined by reduced myocardial blood flow reserve [MBFR]) is associated with high cardiac risk in both men and women in absence of significant coexisting epicardial disease. Whether there is a sex-specific difference in prognostic value of reduced MBFR in patients with a greater burden of coexisting epicardial atherosclerotic disease is not well understood.ObjectivesThe purpose of this study was to examine the association of sex, MBFR, and mortality in consecutive patients with suspected or known coronary artery disease undergoing positron emission tomography myocardial perfusion imaging.MethodsUnique consecutive patients undergoing rubidium (Rb)-82 rest/stress positron emission tomography myocardial perfusion imaging from 2010-2016 were followed for a median of 3.2 years. Multivariable Cox models were built to describe the interaction of sex and MBFR on all-cause and cardiac death for the overall population and stratified by extent of calcified atherosclerosis (none: coronary artery calcium score = 0, subclinical: coronary artery calcium >0, clinical: prior myocardial infarction/percutaneous coronary intervention) and abnormal perfusion (no significant obstructive disease: summed stress score = 0, 1%-9.9%, and ≥10%) at baseline.ResultsAmong 12,594 patients, 52.8% were women. Compared with men, women had a lower prevalence of known coronary artery disease (16.5% vs 29.5%; P < 0.001) and were less likely to undergo revascularization after myocardial perfusion imaging (4.9% vs 9.7%; P < 0.001), but were more likely to have a reduced MBFR of <2 (56.2% vs 50.6%; P < 0.001). There were 1,699 (13.5%) all-cause and 490 (3.9%) cardiac deaths. In fully adjusted Cox models, reduced MBFR was independently associated with higher risk of death (HR per 0.1-U decrease: 1.09 [95% CI: 1.08-1.10]; P < 0.001), but female sex was not (HR: 0.95 [95% CI: 0.85-1.05]; P = 0.27). There was no significant interaction between sex and MBFR on death (P = 0.22) and cardiac death (P = 0.35) overall or in subgroups of patients with clinical, subclinical, and no atherosclerosis or across categories of perfusion abnormality at baseline.ConclusionsThe association between reduced MBFR and higher risk of all-cause and cardiac death did not differ by sex, regardless of extent of coexisting atherosclerosis or perfusion abnormality.     

Uric acid is independent and inversely associated to glomerular filtration rate in young adult Brazilian individuals

Background and aimsUric acid, the end-product of human purine metabolism, is associated with hypertension, diabetes and obesity. It has also been independently associated with the onset of chronic kidney disease in several populations. In this study, the association between serum uric acid (SUA) level and estimated glomerular filtration rate (eGFR) was investigated in healthy individuals belonging to two Brazilian birth cohorts.Methods and resultsData from 3541 to 3482 individuals, aged 30 and 22-years old, respectively, was included. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation based on creatinine measurement. Regression analyses were sex-stratified due to interaction between SUA and sex (p < 0.001) and adjusted for perinatal, cardiometabolic and behavioral variables.We observed an inverse association between eGFR and SUA even after adjustment. In the highest tertile (3rd) of SUA, the eGFR coefficients at 30-years were-0.21 (95%CI -0.24;-0.18) for men and −0.20 (95%CI -0.23; −0.17) for women; at 22-years, were −0.09 (95%CI -0.12;-0.05) for men and −0.13 (95%CI -0.15; −0.10) for women. Higher differences among exponential means (95% CI) of eGFR between the 1st and the 3rd tertile of SUA were seen in older participants, being more pronounced in men. At 22-years, the highest difference was found in women.ConclusionsIn young healthy individuals from a low-middle income country, SUA level was inversely associated with eGFR. Gender-related differences in eGFR according tertiles of SUA were higher in men at 30-years and in women at 22-years.     

SARS-CoV-2 and COVID-19 in diabetes mellitus. Population-based study on ascertained infections,hospital admissions and mortality in an Italian region with ∼5 million inhabitants and ∼250,000 diabetic people

Background and aimsDiabetes conveys an increased risk of infectious diseases and related mortality. We investigated risk of ascertained SARS-CoV-2 infection in diabetes subjects from the Veneto Region, Northeastern Italy, as well as the risk of being admitted to hospital or intensive care unit (ICU), or mortality for COVID-19.Methods and resultsDiabetic subjects were identified by linkage of multiple health archives. The rest of the population served as reference. Information on ascertained infection by SARS-CoV-2, admission to hospital, admission to ICU and mortality in the period from February 21 to July 31, 2020 were retrieved from the regional registry of COVID-19. Subjects with ascertained diabetes were 269,830 (55.2% men; median age 72 years). Reference subjects were 4,681,239 (men 48.6%, median age 46 years). Ratios of age- and gender-standardized rates (RR) [95% CI] for ascertained infection, admission to hospital, admission to ICU and disease-related death in diabetic subjects were 1.31 [1.19–1.45], 2.11 [1.83–2.44], 2.45 [1.96–3.07], 1.87 [1.68–2.09], all p < 0.001. The highest RR of ascertained infection was observed in diabetic men aged 20–39 years: 1.90 [1.04–3.21]. The highest RR of ICU admission and death were observed in diabetic men aged 40–59 years: 3.47 [2.00–5.70] and 5.54 [2.23–12.1], respectively.ConclusionsThese data, observed in a large population of ∼5 million people of whom ∼250,000 with diabetes, show that diabetes not only conveys a poorer outcome in COVID-19 but also confers an increased risk of ascertained infection from SARS-CoV-2. Men of young or mature age have the highest relative risks.     

Sex Differences in 10-Year Outcomes Following STEMI: A Subanalysis From the EXAMINATION-EXTEND Trial

BackgroundShort-term outcomes following ST-segment elevation myocardial infarction (STEMI) in women are worse than in men, with a higher mortality rate. It is unknown whether sex plays a role in very long term outcomes.ObjectivesThe aim of this study was to assess whether very long term outcomes following STEMI treatment are influenced by sex.MethodsEXAMINATION-EXTEND (10-Year Follow-Up of the EXAMINATION Trial) was an investigator-driven 10-year follow-up of the EXAMINATION (A Clinical Evaluation of Everolimus Eluting Coronary Stents in the Treatment of Patients With ST-Segment Elevation Myocardial Infarction) trial, which randomly 1:1 assigned 1,498 patients with STEMI to receive either everolimus-eluting stents or bare-metal stents. The present study was a subanalysis according to sex. The primary endpoint was the composite patient-oriented endpoint (all-cause death, any myocardial infarction, or any revascularization) at 10 years. Secondary endpoints were individual components of the primary endpoint. All endpoints were adjusted for age.ResultsAmong 1,498 patients with STEMI, 254 (17%) were women. Overall, women were older, with more arterial hypertension and less smoking history than men. At 10 years, no difference was observed between women and men for the patient-oriented composite endpoint (40.6% vs 34.2%; adjusted HR: 1.14; 95% CI: 0.91-1.42; P = 0.259). There was a trend toward higher all-cause death in women vs men (27.6% vs 19.4%; adjusted HR: 1.30; 95% CI: 0.99-1.71; P = 0.063), with no difference in cardiac death or other endpoints.ConclusionsAt very long term follow-up, there were no differences in the combined patient-oriented endpoint between women and men, with a trend toward higher all-cause death in women not driven by cardiac death. The present findings underline the need for focused personalized medicine in women after percutaneous revascularization aimed at both cardiovascular and sex-specific risk factor control and targeted treatment. (10-Years Follow-Up of the EXAMINATION Trial [EXAMINAT10N]; NCT04462315)     

Positive association between body fat percentage and hyperuricemia in patients with hypertension: The China H-type hypertension registry study

Background and aimsThe relationship between the body fat percentage (BFP) and hyperuricemia is still unknown in different gender subjects. The purpose of this study was to determine the magnitude of the association between the BFP and the presence of hyperuricemia in the sex-specific group among hypertensive patients.Methods and resultsWe conducted a cross-sectional study enrolling 14,234 hypertensive participates from the Chinese Hypertension Registry Study. Body fat percentage (BFP) was calculated by simple anthropometric parameters. Hyperuricemia was defined as serum uric acid (SUA) level 420 umol/L in men and 360 umol/L in women. The mean BFP was 24.5% in men and 37.1% in women. Multiple logistic analyses showed that the relationship between BFP with the risk of hyperuricemia in a dose-dependent manner among both men (odds ratio [OR] 1.07, 95% CI 1.06, 1.09) and women (OR 1.08, 95% CI 1.06, 1.09) in the fully adjusted model. Subgroup analyses showed the positive association between BFP and the risk of hyperuricemia was consistent in all stratification subgroups (all P for interaction >0.05).ConclusionFor patients with hypertension, BFP was positively associated with an increased risk of hyperuricemia among both men and women.     

Association between body mass index,waist circumference,and relative fat mass with the risk of first unprovoked venous thromboembolism

Background and aimsObesity defined by body mass index (BMI) is independently associated with venous thromboembolism (VTE). Abdominal obesity, defined by waist circumference, is a predictor of cardiovascular events. Recently, relative fat mass (RFM) was proposed as a marker of cardiovascular risk. We assessed the role of three different measures of obesity to predict unprovoked VTE in a longitudinal study.Methods and resultsMoli-sani is a prospective cohort study carried out in the general population of the Molise region, Italy. A total of 23,538 individuals (48% men, age 55.4 years) enrolled between 2005 and 2010 were eligible. Patients on anticoagulant treatment were excluded. BMI ≥30 kg/m² defined obesity, waist circumference >102 cm for men or 88 cm for women defined abdominal obesity, tertiles of RFM were compared. The long-term incidence of first unprovoked VTE during follow-up was assessed. Overall, 29.6% individuals were obese and 44.2% had abdominal obesity. A total of 66 first unprovoked VTE events were diagnosed during a median follow-up of 8.2 years. After multivariable Cox regression analysis, the risk of unprovoked VTE was significantly higher in obese participants (HR 1.89, 95% CI 1.16–3.07) than in participants with BMI <30; in subjects with abdominal obesity than with normal waist circumference (HR 2.19, 1.26–3.81); and in subjects with third vs first RFM tertile index (HR 2.46, 1.15–5.28). The areas under the curves for the models including the three obesity indexes were comparable.ConclusionsThree indexes of obesity based on BMI, waist circumference or RFM similarly predict first occurrence of unprovoked VTE.     

Pre-Menopausal Breast Fat Density Might Predict MACE During 10 Years of Follow-Up: The BRECARD Study

ObjectivesThis study sought to determine whether the breast gland adipose tissue is associated with different rates of major adverse cardiac events (MACEs) in pre-menopausal women.BackgroundTo our knowledge, no study investigated the impact of breast adipose tissue infiltration on MACEs in pre-menopausal women.MethodsProspective multicenter cohort study conducted on pre-menopausal women >40 years of age without cardiovascular disease and breast cancer at enrollment. The study started in January 2000 and ended in January 2009, and the end of the follow-up for the evaluation of MACEs was in January 2019. Participants underwent mammography to evaluate breast density and were divided into 4 groups according to their breast density. The primary endpoint was the probability of a MACE at 10 years of follow-up in patients staged for different breast deposition/adipose tissue deposition.ResultsThe propensity score matching divided the baseline population of 16,763 pre-menopausal women, leaving 3,272 women according to the category of breast density from A to D. These women were assigned to 4 groups of the study according to baseline breast density. At 10 years of follow-up, we had 160 MACEs in group 1, 62 MACEs in group 2, 27 MACEs in group 3, and 16 MACEs in group 4. MACEs were predicted by the initial diagnosis of lowest breast density (hazard ratio: 3.483; 95% confidence interval: 1.476 to 8.257). Further randomized clinical trials are needed to translate the results of the present study into clinical practice. The loss of ex vivo breast density models to study the cellular/molecular pathways implied in MACE is another study limitation.ConclusionsAmong pre-menopausal women, a higher evidence of adipose tissue at the level of breast gland (lowest breast density, category A) versus higher breast density shows higher rates of MACEs. Therefore, the screening mammography could be proposed in overweight women to stage breast density and to predict MACEs. (Breast Density in Pre-menopausal Women Is Predictive of Cardiovascular Outcomes at 10 Years of Follow-Up [BRECARD]; NCT03779217)