Fracture Risk Assessment Tool-Based Screening for Osteoporosis in Older Adults in Resource-Limited Settings.

PURPOSE: Osteoporosis is a pressing public health concern among older adults, contributing to substantial mortality and morbidity rates. Low- to middle-income countries (LMICs) often grapple with limited access to dual-energy X-ray absorptiometry (DXA), the gold standard for early osteoporosis detection. This study aims to assess the performance of the FRAX® score as a population-wide screening tool for predicting osteoporosis risk, rather than fracture, in individuals aged 50 and above within an LMIC context. METHODS: This retrospective cohort study (n=864) assessed the performance of the FRAX® score for predicting osteoporosis risk using comparative c-statistics from Receiver Operating Characteristic (ROC) curves. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated, with p-values <0.05 indicating statistically significant. RESULTS: The 10-year FRAX® probability for hip fracture, calculated without bone mass density (BMD), exhibited significantly superior performance compared to the 10-year FRAX® probability for major fracture in predicting osteoporosis risk (AUROC: 0.71 versus 0.67, p<0.001). Within 2 to 10 years of follow-up, the 10-year FRAX® probability for hip fracture showed both greater predictive performance and net benefit in the decision curve compared to the FRAX® 10-year probability for major fracture. A newly established cutoff of 1.9 % yielded a negative predictive value of 92.9 % (95 %CI: 90.4-94.8 %) for the 10-year FRAX® probability for hip fracture. CONCLUSION: The 10-year FRAX® probability for hip fracture estimated without BMD emerges as an effective 10-year screening tool for identifying osteoporosis risk in aged 50 and older, especially when confronted with limited access to DXA scans in LMICs. MINI ABSTRACT: The Fracture Risk Assessment Tool score performance as an osteoporosis screening tool was assessed in areas with limited dual-energy X-ray access. The hip fracture probability showed better performance than major fracture probability within 2 to 10 years. The tool emerges as effective for screening osteoporosis risk in individuals over 50.

The role of SGLT2i in attenuating residual cardiovascular risk through blood pressure-lowering: mechanistic insights and perspectives.

Sodium glucose cotransporter 2 inhibitors (SGLT2) have been increasingly pursued as a promising target for addressing residual cardiovascular risk. Prior trials demonstrated that SGLT2i not only promotes glucose-lowering, but also improves endothelial dysfunction, adiposity, fluid overload, and insulin sensitivity thus contributing to hemodynamic changes implicated in its cardiorenal benefits. The mechanisms in the effect of SGLT2i on blood pressure and their potential role in preventing cardiovascular events are hereby revised.

Pharmacokinetic Properties of Dapagliflozin in Hemodialysis and Peritoneal Dialysis Patients.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors attenuate incident cardiovascular outcomes, irrespective of baseline GFR, in conservatively managed CKD. As this condition inexorably progresses to demanding KRT, drug withdrawal is supported by the current lack of evidence of safety of SGLT2 inhibitors in dialysis. METHODS: This study was a prospective, single-center, open-label trial ( ClinicalTrials.gov identifier: NCT05343078 ) aimed at assessing the pharmacokinetic properties and safety of dapagliflozin in patients with kidney failure on regular dialysis regimens compared with those with type 2 diabetes and age- and sex-matched controls with normal kidney function. Peripheral blood samples were collected from both groups every 30 minutes for 4 hours and again after 48 hours after ingestion of dapagliflozin 10 mg, which occurred immediately before dialysis session initiation in the kidney failure group. This protocol occurred in drug-naïve patients and again after six daily doses of dapagliflozin to assess whether the drug had accumulated. The plasma and dialysate levels of dapagliflozin at each time point were determined by liquid chromatography and used to calculate pharmacokinetics parameters (peak concentration [C max ] and area under the plasma concentration-versus-time curve) for each participant. RESULTS: Dapagliflozin C max was 117 and 97.6 ng/ml in the kidney failure and control groups, respectively, whereas the corresponding accumulation ratios were 26.7% and 9.5%. No serious adverse events were reported for either group. Dapagliflozin recovered from dialysate corresponded to 0.10% of the administered dose. CONCLUSIONS: In patients with kidney failure on dialysis, dapagliflozin was well tolerated, was slightly dialyzable, and had nonaccumulating pharmacokinetic properties. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Pharmacokinetics and Dialyzability of Dapagliflozin in Dialysis Patients (DARE-ESKD 1), NCT05343078.

Subclinical Hypothyroidism is Not Associated with Femoral Osteoporosis in Individuals Aged 50 Years or Older.

BACKGROUND: Thyroid dysfunction and osteoporosis are conditions strongly associated with aging, and the prevalence of both conditions is expected to increase in the coming decades. Thyroid hormones regulate bone metabolism, and the role of subclinical hypothyroidism on bone mineral density (BMD) is still controversial. Hence, this study aims to assess the association of subclinical hypothyroidism with femoral osteopenia and osteoporosis in individuals aged 50 years or older. METHODOLOGY: This retrospective cohort study was carried out with 864 outpatients having at least one result for TSH levels before the first record of dual-energy X-ray absorptiometry (DXA). The primary endpoints were osteopenia (-2.5 standard deviation (SD)

Defective Allele of the Neuronal Nitric Oxide Synthase Gene Increases Insulin Resistance During Acute Phase of Myocardial Infarction.

BACKGROUND: Glycemic disorders are strong predictors of mortality in ST-elevation myocardial infarction (STEMI) patients, and disruption in nitric oxide (NO) production is associated with insulin-resistant states. We evaluated whether a defective allele of the neuronal nitric oxide synthase (nNOS) gene (NOS1) might influence insulin response and blood-glucose balance during the acute phase of STEMI and if post-infarction total plasma-NO levels and vasodilation scores varied across nNOS genotypes. METHODS: Consecutive patients with STEMI (n=354) underwent clinical evaluations and genotyping for the promoter variation rs41279104. In-hospital clinical and blood evaluations were performed at admission and five days after STEMI, with glycemic, insulinemic, and disposition indices assessed at the same times. Flow-mediated dilation (FMD) was assessed by reactive hyperemia on the 30th day. RESULTS: Homozygotes for the defective allele (A) showed lower glycemia and insulin sensitivity on day 1 while showing the highest ß-cell function and no changes in the circulating NO pool, which is compatible with hyperresponsive ß cells counteracting the inherent glucose-resistant state of AA patients. At day 5, glycemic scores had shifted to indicate greater insulin sensitivity among A homozygotes, paralleled by a significant yet poor increase in NO bioavailability compared to that among G carriers. All in all, defective homozygotes showed greater insulin resistance at admission that had reversed by 5 days after STEMI. Even so, A carriers developed lower FMD scores compared to G homozygotes after the acute phase. CONCLUSION: A defective nNOS allele (and due decline in NO production) seemed to elicit a hyperinsulinemia response to compensate for an insulin-resistant state during the acute phase of STEMI and to be associated with poor endothelial function after the acute phase.

Lower bone mass is associated with subclinical atherosclerosis, endothelial dysfunction and carotid thickness in the very elderly.

BACKGROUND AND AIMS: Osteoporosis and coronary heart disease (CHD) are very common conditions among elderly people, and both represent a public health concern due to their prognostic consequences. Osteoporosis and CHD share many risk factors and pathophysiological mechanisms, such as calcification pathways. Clinical evidence associates lower bone mass with cardiovascular diseases and endothelial dysfunction. Hence, this study aims to investigate whether bone mass density is associated with subclinical atherosclerosis and/or endothelial dysfunction in the very elderly. METHODS: We performed a cross-sectional study of cohort enrolled individuals, ages 80 years or older (n = 208), who had never manifested cardiovascular diseases. Medical evaluation, blood tests, flow-mediated dilation (FMD), carotid intimal-media thickness (IMT), Dual Energy X-ray Absorptiometry (DEXA) and Coronary Calcium Score (CCS) were obtained. Odds Ratio (OR) was calculated by multivariate logistic regression models using CCS, FMD and IMT categories. Adjustments for covariates were done. RESULTS: Overall bone mass was independently and inversely associated with CCS categories [OR:1.68(1.16-8.85); p = 0.024] and IMT categories [OR:2.97(1.11-7.90); p = 0.030]. Conversely, overall bone mass was independent and directly associated with FMD categories [OR:2.73(1.36-70.39); p = 0.023]. CONCLUSIONS: This study indicates that overall bone mass is independently and inversely associated with subclinical atherosclerosis, endothelial dysfunction and thickness of carotid in the very elderly.

Statin Short-term Inhibition of Insulin Sensitivity and Secretion During Acute Phase of ST-Elevation Myocardial Infarction.

Hyperglycemia during myocardial infarction (MI) has a strong and direct association with mortality. In stable patients and experimental models, statins favor the elevation of glycaemia. The present study investigated whether short-course treatment with statins during MI can influence glucose homeostasis and thus the clinical outcome. In this prospective study, euglycemic hyperinsulinemic clamp (EHC) was performed at second (D2) and sixth (D6) day after MI in patients randomized to simvastatin (S)10 or 80 mg/day during hospitalization (n = 27). In addition, patients (n = 550) were treated without (WS) or with simvastatin (S) at 20, 40 or 80 mg/day had HOMA2S on admission (D1) and fifth (D5) day after MI. According to EHC, insulin sensitivity increased by 20 ± 60% in S10 and decreased by -6 ± 28% in S80 (p = 0.025). Consistently, the changes in HOMA2S between D1 and D5 were 40 ± 145% (WS), 22 ± 117% (S20), 16 ± 61% (S40) and -2% ± 88% (S80) (p = 0.001). In conclusion, statin during the acute phase of MI reduces insulin sensitivity in a dose-dependent manner.

Omega-3 intake is associated with attenuated inflammatory response and cardiac remodeling after myocardial infarction.

BACKGROUND: Myocardial infarction (MI) elicits an intense acute inflammatory response that is essential for cardiac repair. However, an excessive inflammatory response also favors myocardial apoptosis, cardiac remodeling, and cardiovascular mortality. Omega-3 polyunsaturated fatty acids (ω-3) bear anti-inflammatory effects, which may mitigate the inflammatory response during MI. This study investigated whether ω-3 intake is associated with attenuation of the MI-related inflammatory response and cardiac remodeling. METHODS: ST-elevation MI (STEMI) patients (n = 421) underwent clinical, biochemical, nutritional, 3D echocardiogram, Cardiac Magnetic Resonance imaging (CMRi) at 30 days and 3D echocardiogram imaging at six months after the MI. Blood tests were performed at day one (D1) and day five (D5) of hospitalization. Changes in inflammatory markers (ΔD5-D1) were calculated. A validated food frequency questionnaire estimated the nutritional consumption and ω-3 intake in the last 3 months before admission. RESULTS: The intake of ω-3 below the median (< 1.7 g/day) was associated with a short-term increase in hs-C-reactive protein [OR:1.96(1.24-3.10); p = 0.004], Interleukin-2 [OR:2.46(1.20-5.04); p = 0.014], brain-type natriuretic peptide [OR:2.66(1.30-5.44); p = 0.007], left-ventricle end-diastolic volume [OR:5.12(1.11-23.52)]; p = 0.036] and decreases in left-ventricle ejection fraction [OR:2.86(1.47-6.88); p = 0.017] after adjustment for covariates. No differences were observed in the extension of infarcted mass obtained by CMRi. CONCLUSION: These findings suggest that a reduced daily intake of ω-3 may intensify outcome-determining mechanisms after STEMI, such as acute inflammatory response and late left ventricular remodeling. TRIAL REGISTRATION: Clinical Trial Registry number and website: NCT02062554 .