Use Of Thiazide Diuretics Research Articles

Causal relationship between antihypertensive drugs and Hashimoto's thyroiditis: a drug-target Mendelian randomization study.

Recent studies have indicated a potential association of hypertension with Hashimoto's thyroiditis (HT) and other autoimmune diseases, yet the impact of antihypertensive drugs on HT risk is not well understood. We employed a drug-target Mendelian randomization approach to investigate the prolonged impact of 9 classes of antihypertensive medications on HT susceptibility in European and Asian populations. Genetic variants close to or within genes associated with the drug targets and systolic blood pressure (SBP) were utilized to mimic the effects of antihypertensive medications. We focused on drugs linked to a lower risk of coronary artery disease for our main analysis. We gathered genetic data on SBP and HT risk from comprehensive genome-wide association studies available for European and Asian groups. For a supplementary analysis, we used expression quantitative trait loci (eQTLs) related to drug target genes as proxies. Our analysis revealed that the use of calcium channel blockers (CCBs) is linked to a reduced risk of HT in both European (OR [95% CI]: 0.96 [0.95 to 0.98] per 1 mmHg decrease in SBP; p = 3.51×10-5) and Asian populations (OR [95% CI]: 0.28 [0.12, 0.66]; p = 3.54×10-3). Moreover, genetically mimicking the use of loop diuretics (OR [95% CI]: 0.94 [0.91, 0.97]; p = 3.57×10-5) and thiazide diuretics (0.98 [0.96, 0.99]; p = 3.83×10-3) showed a significant association with a decreased risk of HT only in European population. These outcomes were confirmed when eQTLs were employed to represent the effects of antihypertensive medications. The study suggests that CCBs and diuretics could potentially reduce the risk of HT in different populations. Additional research is needed to assess the feasibility of repurposing antihypertensive medications for the prevention of HT.

8168 From Salt to the Sella- Discovering Empty Sella Syndrome as a Rare Cause of Severe Hyponatremia

Abstract Disclosure: P. Vemparala: None. S. Challagulla: None. Introduction: Hyponatremia is a common electrolyte disorder with potentially life-threatening consequences. Careful evaluation of hyponatremia can uncover significant underlying conditions. We present an interesting case of a patient who presented with symptoms of severe hyponatremia and a workup led us to the discovery of empty sella syndrome as the etiology. Case Presentation: A 54-year-old male with hypertension presented with 2 days of left-sided headache, blurred vision, generalized weakness, and vomiting. Pertinent medication history revealed the use of thiazide diuretic, bupropion and varenicline. Physical examination was unremarkable. Laboratory data showed severe hyponatremia with a serum sodium of 118 meq/L. Initial improvement with fluids was followed by a decline (106-112 meq/L). CT head without contrast showed a prominent empty sella turcica. Workup revealed urine osmolality and elevated urine sodium. A low AM cortisol level of 1.0 mcg/dl (reference range- AM- 7.0 - 25.0 mcg/dl), and decreased adrenocorticotropic hormone (ACTH) level of 5.2 pg/ml (reference range- 7.2 - 63.3 pg/ml) suggested secondary adrenal insufficiency. All other anterior pituitary hormones were normal. Brain magnetic resonance imaging (MRI) confirmed the diagnosis of partial empty sella. Treatment with hypertonic saline, fluid restriction, and steroids led to symptom resolution. Conclusion: Empty sella syndrome is a rare pituitary condition that can be primary- characterized by herniation of the subarachnoid space within the sella, or secondary- which occurs when the sella is empty due to damage to the pituitary gland by tumor, radiation, etc. It can cause potential hypopituitarism, be asymptomatic, or present with symptoms of raised intracranial pressure. In patients with hypopituitarism, deficiencies of ACTH and TSH are rarer and appear to be more common with a complete empty sella. This case emphasizes the need for a comprehensive hyponatremia workup, awareness of secondary adrenal insufficiency, and recognition of the life-threatening potential of even partial empty sella syndrome when untreated. Presentation: 6/1/2024

#2679 Prediction of acute eGFR decline after first initiation of RASI inhibitors and its impact on clinical outcomes

Abstract Background and Aims The objective of this study is to investigate the correlation between acute eGFR (estimated glomerular filtration rate) decline after initiation of ACEI (angiotensin-converting enzyme inhibitor)/ARB (angiotensin receptor blocker) medications and clinical outcomes in a real-world setting. Additionally, we aim to establish a risk prediction model to identify high-risk individuals who are more likely to experience a rapid decline in eGFR after drug initiation. Method A total of 2026 adult new users of ACEI/ARB were selected from the China Renal Data System (CRDS). Patients in acute clinical states and those using nephrotoxic drugs were excluded, and it was required that patients had at least one creatinine measurement during the baseline period and one week to four weeks after drug initiation. Cox proportional hazards models were used to compare the relative risks of adverse long-term outcomes in patients with different degrees of acute eGFR decline. A multivariable logistic regression model was employed to analyze the factors influencing acute eGFR decline. Lasso regression was used to select predictive factors, resulting in a logistic regression model with 18 predictive factors. Results Among the 2026 patients, 1148 (57%), 473 (23%), and 405 (20%) experienced eGFR decline <5% or increase, 5-20% decline, and ≥20% decline, respectively, after initiation of RASI (renin-angiotensin system inhibitor). Following adjustment for multiple variables, an eGFR decline ≥20% was found to be associated with a higher risk of long-term renal disease progression, with a hazard ratio of 1.84 (95% confidence interval 1.19-2.85), but not significantly associated with an increased risk of all-cause mortality and cardiovascular events. Factors associated with an eGFR decline ≥20% after RASI initiation included higher BMI and Charlson index, more severe proteinuria, lower hemoglobin levels, presence of hypertension, diabetic nephropathy, arrhythmias, and concomitant use of thiazide diuretics or loop diuretics. The predictive model had a C-statistic of 0.75. Conclusion This study demonstrates that a short-term eGFR decline after RASI initiation is associated with a higher risk of long-term renal disease progression but not significantly associated with increased risks of all-cause mortality and cardiovascular events. We have developed a prediction model to estimate the risk of eGFR decline ≥20% after the initial use of RASI, which can aid clinicians in identifying patients with poorer renal outcomes following RASI initiation and facilitate timely intervention.

New use of thiazide diuretics vs. nonthiazide antihypertensive drugs was linked to hyponatremia over 2 y.

Andersson NW, Wohlfahrt J, Feenstra B, et al. Cumulative incidence of thiazide-induced hyponatremia: a population-based cohort study. Ann Intern Med. 2024;177:1-11. 38109740.

Pre-post implementation study of chronic diuretic clinical practice guideline for bronchopulmonary dysplasia in preterm infants

BackgroundChronic diuretics are frequently used (off-label) in preterm infants to manage evolving or established bronchopulmonary dysplasia (BPD). Chronic diuretic use, however, is limited by tolerance with no long-term safety and efficacy data, leading to wide variation in its use in preterm infants. ObjectiveTo determine the impact of the chronic diuretic clinical practice guideline (CPG) on the patterns of diuretic use, severity of BPD, and hospital length of stay (LOS) in preterm infants born less than 32 weeks gestation. MethodsSingle-center retrospective pre-post CPG cohort study in a level IV neonatal intensive care unit. Chronic diuretic CPG was implemented in November 2021 and the data was collected one year before (Pre-CPG) and one year after (Post-CPG). ResultsIn total, 73 infants (39 Pre-CPG, and 34 Post-CPG) were identified. There were no significant differences in patient characteristics at birth or in the use and duration of respiratory support between the two groups. Compared to Pre-CPG, the frequency of thiazide diuretic use was not decreased in Post-CPG (30.8 vs. 20.6 %, p = 0. 42), but the duration of use was significantly reduced (35 vs. 6 days, p = 0.01). Both frequency (20.5 vs. 2.9 %) and duration (28.5 vs. 4 days) of spironolactone were reduced in the Post-CPG (p < 0.05). Furosemide exposure (69.2 vs. 41.2 %, p = 0.02) and total doses [3.0 (0.0–8.0) vs. 0.0 (0.0–2.3), p = 0.003] were also significantly reduced in the Post-CPG. The incidence of any BPD at 36 weeks and LOS were similar between groups, while the incidence of moderate/severe BPD and home oxygen use were decreased in the Post-CPG. ConclusionsChronic diuretic CPG was associated with a reduction in diuretic exposure in preterm infants

Identification of Risk Factors for Gliptin-associated Bullous Pemphigoid among Diabetic Patients.

Drug-associated bullous pemphigoid has been shown to follow long-term gliptin (dipeptidyl-peptidase 4 inhibitors) intake. This study aimed at identifying risk factors for gliptin-associated bullous pemphigoid among patients with type 2 diabetes. A retrospective study was conducted in a tertiary centre among diabetic patients exposed to gliptins between the years 2008-2021. Data including demographics, comorbidities, medications, and laboratory results were collected using the MDClone platform. Seventy-six patients with type 2 diabetes treated with dipeptidyl-peptidase 4 inhibitors who subsequently developed bullous pemphigoid were compared with a cohort of 8,060 diabetic patients exposed to dipeptidyl-peptidase 4 inhibitors who did not develop bullous pemphigoid. Based on a multivariable analysis adjusted for age and other covariates, Alzheimer's disease and other dementias were significantly more prevalent in patients with bullous pemphigoid (p = 0.0013). Concomitant use of either thiazide or loop diuretics and gliptin therapy was associated with drug-associated bullous pemphigoid (p < 0.0001 for both). While compared with sitagliptin, exposure to linagliptin and vildagliptin were associated with bullous pemphigoid with an odds ratio of 5.68 and 6.61 (p < 0.0001 for both), respectively. These results suggest gliptins should be prescribed with caution to patients with type 2 diabetes with coexisting Alzheimer's and other dementias, or patients receiving long-term use of thiazides and loop diuretics. The use of sitagliptin over linagliptin and vildagliptin should be preferred in these patients.

Acetazolamide and Hydrochlorothiazide in Patients With Acute Decompensated Heart Failure: Insights From Recent Trials.

Acetazolamide and thiazide diuretics have been combined with loop diuretics to overcome diuretic resistance in heart failure patients. However, recent studies have assessed the upfront combination of acetazolamide and hydrochlorothiazide with loop diuretics in hospitalized patients with acute decompensated heart failure without loop diuretic resistance. We reviewed two recent randomized controlled trials on the upfront use of acetazolamide and thiazide diuretics in acute decompensated heart failure, respectively. When the two trials on acetazolamide are considered together, adding oral or intravenous acetazolamide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and natriuresis. However, the effects were significantly higher in patients with serum bicarbonate ≥ 27 mmol/L and those with higher baseline glomerular filtration rate (GFR). Similarly, when the two trials on thiazide diuretics are considered together, adding hydrochlorothiazide to loop diuretics in decompensated heart failure patients resulted in increased diuresis and weight loss. However, it increases the risk of impaired renal function. When all the trials are considered together, the upfront use of acetazolamide may be helpful in carefully selected patients, including patients with underlying elevated bicarbonate levels (≥ 27 mmol/L) and those with good renal function (GFR > 50). Conversely, though the upfront use of thiazide diuretic added to intravenous furosemide improved diuretic response in acute decompensated heart failure, it causes an increased risk of worsening renal function and lack of clear evidence of reducing hospital length of stay.

Diuretic Use and Serum Phosphate: Rotterdam Study and UK Biobank

Abstract Purpose Hypophosphatemia (serum phosphate &amp;lt; 0.80 mmol/L) leads to musculoskeletal complaints. The most common drugs linked to hypophosphatemia are thiazide and loop diuretics, but studies in the general population are lacking. Our aim was to study associations between diuretic use and serum phosphate in the Rotterdam Study (RS), a population-based cohort study, with replication in UK Biobank (UKBB). Methods Associations between thiazide and loop diuretic use and serum phosphate and odds of hypophosphatemia were analyzed with cross-sectional multivariate linear and logistic regression in participants without chronic kidney disease in the RS and UKBB. Analyses were adjusted for age, sex, and body mass index (BMI) and pooled in 3 RS cohorts with further adjustment for cohort and serum potassium, which was not available in UKBB. Results Thiazide diuretics were associated with lower serum phosphate in both sexes. This association lost significance in RS females after adjustment for BMI and in males after adjustment for serum potassium. Thiazide diuretics increased odds of hypophosphatemia in females in both cohorts and in males in UKBB only. Loop diuretics were associated with lower serum phosphate in females but not males. Adjustment for BMI attenuated these associations. Associations between loop diuretics and increased odds of hypophosphatemia in females lost significance after BMI adjustment. Conclusion Thiazides, but not loop diuretics, and increased BMI and decreased serum potassium should be considered as contributing factors in subjects with hypophosphatemia. Further studies are needed to replicate the findings and elucidate the potential role of hypokalemia as a mediator of this effect.

Optimal Medical Management of Atherosclerotic Intracranial Stenosis.

Reducing the high risk of recurrent stroke in patients with symptomatic intracranial atherosclerotic stenosis (sICAS) has proven to be challenging, but aggressive medical management, with intensive risk factor control and antithrombotic therapy, has been shown to be beneficial. High-intensity statins are recommended for patients with atherosclerotic stroke, including sICAS. Ezetimibe and PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors are beneficial for those who fail to reach low-density lipoprotein targets or those with statin intolerance. The treatment target for sICAS is low-density lipoprotein <70 mg/dL. In neurologically stable patients, blood pressure should be treated to goal <140/90 mm Hg with the use of thiazide diuretics, angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers preferentially. For those with diabetes, treat to goal hemoglobin A1C ≤7% for most patients through combination of diet, insulin, and hypoglycemic drugs. Some degree of physical activity (eg, walking, stationary biking with arms or legs, etc) should be encouraged in all patients with sICAS who are not severely disabled. A minimum of 10 minutes of moderate-intensity aerobic activity 4 times a week is recommended for patients who are capable of exercise. For all patients with severe sICAS (70%-99% stenosis), dual antiplatelet therapy for up to 90 days followed by single antiplatelet agent is recommended.

Are thiazide diuretics ineffective with a glomerular filtration rate lower than 50 ml/min?

Many treatment guidelines do not recommend the use of thiazide diuretics or thiazide-like diuretics in patients with impaired kidney function. The rationale is apresumed lack of efficacy of these diuretics in cases of a reduced glomerular filtration rate (GFR); however, this paradigm could not be verified in recent studies. Thiazide diuretics and thiazide-like diuretics are also effective in patients with substantially reduced GFR, which pertains to natriuresis, correction of volume overload and lowering of blood pressure; however, in patients with chronic kidney disease loop diuretics can control volume overload more rapidly. Particularly effective is the combination of loop diuretics with thiazide diuretics or thiazide-like diuretics in patients with markedly limited GFR. Therefore, thiazide diuretics and thiazide-like diuretics should also be prescribed even for patients with higher grade impairments of kidney function (chronic kidney disease in stages3-5), except for anuric patients where they are ineffective.

Thiazide diuretics and primary hyperparathyroidism.

Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect renal calcium handling by increasing calcium reabsorption, leading to hypocalciuria. The effect that thiazide diuretics exert on parathyroid hormone secretion is controversial. Some studies found parathyroid hormone levels were suppressed with the use of thiazide diuretics, while others found that thiazides were associated with initial parathyroid hormone suppression followed by raised parathyroid hormone levels. This makes the relationship between thiazide diuretics and primary hyperparathyroidism interesting. If a patient is taking thiazide diuretics, this may make it harder to establish the aetiology of hypercalcaemia and may unmask normocalcaemic or mild primary hyperparathyroidism. Thiazide diuretics may have a beneficial role in the diagnosis of patients with concomitant hyperparathyroidism and hypercalciuria by distinguishing secondary hyperparathyroidism caused by hypercalciuria from normocalcaemic primary hyperparathyroidism. In addition, thiazide diuretics may have a role in managing patients with primary hyperparathyroidism who have an indication for parathyroidectomy in view of significant hypercalciuria, but are unfit for surgery.

The determinants of fasting and post-load non-esterified fatty acids in older adults: The cardiovascular health study

AimNon-esterified fatty acids (NEFA) are potential targets for prevention of key cardiometabolic diseases of aging, but their population-level correlates remain uncertain. We sought to identify modifiable factors associated with fasting and post-load NEFA levels in older adults. MethodsWe used linear regression to determine the cross-sectional associations of demographic, anthropometric, and lifestyle characteristics and medication use with serum fasting and post-load NEFA concentrations amongst community-dwelling older adults enrolled in the Cardiovascular Health Study (n = 1924). ResultsFasting NEFA levels generally demonstrated a broader set of determinants, while post-load NEFA were more consistently associated with metabolic factors. Waist circumference and weight were associated with higher fasting and post-load NEFA. Cigarette smoking and caffeine intake were associated with lower levels of both species, and moderate alcohol intake was associated with higher fasting levels whereas greater consumption was associated with lower post-load levels. Unique factors associated with higher fasting NEFA included female sex, higher age, loop and thiazide diuretic use and calcium intake, while factors associated with lower fasting levels included higher educational attainment, beta-blocker use, and protein intake. Hours spent sleeping during the daytime were associated with higher post-load NEFA, while DASH score was associated with lower levels. ConclusionFasting and post-load NEFA have both common and unique modifiable risk factors, including sociodemographics, anthropometric, medications, and diet. Post-load NEFA were particularly sensitive to metabolic factors, while a broader range of determinants were associated with fasting levels. These factors warrant study as targets for lowering levels of NEFA in older adults.

Association between antihypertensive medicine use and risk of ovarian cancer in women aged 50 years and older

BackgroundEpithelial ovarian cancer (EOC) has few modifiable risk factors. There is evidence that some antihypertensive medicines may have cancer preventive and/or therapeutic actions; therefore, we assessed the associations between use of different antihypertensive medicines and risk of specific EOC histotypes. MethodsOur nested case-control study of linked administrative health data included 6070 Australian women aged over 50 years diagnosed with EOC from 2004 to 2013, and 30,337 matched controls. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between ever use of each antihypertensive medicine group, including beta-adrenergic blockers, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, calcium channel blockers, diuretics, and alpha blockers, and the risk of EOC overall and separately for the serous, endometrioid, mucinous, clear cell and other histotypes. ResultsWe found that most antihypertensive medicines were not associated with risk of EOC. However, women who used calcium channel blockers had a reduced risk of serous EOC (OR= 0.89, 95 % CI:0.81,0.98) and use of combination thiazide and potassium-sparing diuretics was associated with an increased risk of endometroid EOC (OR= 2.09, 95 % CI:1.15,3.82). ConclusionOur results provide little support for a chemo-preventive role for most antihypertensives, however, the histotype-specific associations we found warrant further investigation.

Association of Thiazide Diuretics With Diabetes Progression, Kidney Disease Progression, Cardiovascular Outcomes, and Death Among Patients With Diabetes Who Initiate Statins

Statins have been associated with diabetes mellitus (DM) progression but their cardiovascular benefit in patients with DM outweigh the harm. However, the effects of concurrent use of other medications that similarly increase blood glucose level, such as thiazide diuretics, are not well studied. This study aimed to evaluate the association of concurrent use of thiazide diuretics and statins on DM progression, cardiovascular and renal outcomes, and death in patients with DM. This is a retrospective cohort study of Veterans with DM who initiated statins between 2003 and 2015. The cohort comprised thiazide users (concomitantly used thiazides and statins for ≥6months) and active comparators (concomitantly used calciun channel blockers [CCB] but not thiazides and statins for ≥6months). We excluded patients who were <18 years old, with chronic kidney disease stage 4 or worse, or used loop diuretics. We propensity-score-matched comparison groups on 99 baseline characteristics including demographics, healthcare utilization, co-morbidities, cardiovascular and co-morbidity scores, vital signs, laboratory data, and medication class usage. Outcomes were: (1) DM progression (new insulin initiation, increase in the number of glucose-lowering medication classes, and hyperglycemic episodes); (2) kidney disease progression (doubling of serum creatinine, incidence of chronic kidney disease stage 5, initiation of renal replacement therapy, and incidence of diabetic nephropathy); (3) cardiovascular outcomes (acute myocardial infarction, stroke, cardiac arrest); and (4) total mortality. From 297,967 statin users (228,509 Thiazide-statin users and 69,458 active comparators), we successfully matched 67,614 pairs. In comparison to active comparators, thiazide-statin users had increased risk of DM progression (65.6% in CCB group vs 68.1% in thiazide group; odds ratio [OR]: 1.12, 95% confidence interval [CI]: 1.09 to 1.15), decreased risk of kidney progression (16.9% in CCB group vs 16.5 in thiazide group; OR: 0.97, 95% CI: 0.94 to 0.99), decreased risk of cardiovascular outcomes (15.7% in CCB group vs 14.6% in thiazide group; OR: 0.92, 95% CI: 0.89 to 0.95), and similar risk of total mortality (19.7% in each group; OR: 1.00, 95% CI: 0.98 to 1.03). This study attempted to answer an important clinical question whether thiazide diuretics should be discontinued or substituted upon statin initiation. Our results showed that concurrent use of statin and thiazides in patients with DM was associated with DM progression but with less kidney progression and cardiovascular outcomes and no difference in mortality. Clinicians should closely monitor DM control when thiazides and statins are used concurrently.

#4893 THE INCIDENCE, RISK FACTORS AND OUTCOMES OF ACUTE KIDNEY INJURY AFTER MINOR LOWER LIMB AMPUTATIONS

Abstract Background and Aims Minor lower limb amputations (toe amputations and/or amputations distal to or through the tarsometatarsal joint), are limb and potentially lifesaving procedures. However, they are associated with serious adverse events including acute kidney injury (AKI). The aim of this study was to determine the incidence of AKI after such interventions, identify potential risk factors and assess impact on patient survival. Method This was a single centre retrospective study involving patients who underwent minor lower limb amputations at Mater Dei Hospital Malta between January and December 2019. Patient and procedure details were obtained from hospital records. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula. Chronic kidney disease (CKD) was defined as per Kidney Disease: Improving Global Outcomes (KDIGO) criteria. AKI was defined using Acute Kidney Injury Network (AKIN) criteria or KDIGO criteria if day 7 serum creatinine was available. Statistical analysis was performed using SPSS Statistics for Windows v21.0 (IBM Corp.). Results A total of 201 patients were included; males 69.7%, mean age 70.4 ±11.5 years, 87.1% had diabetes mellitus, 71.1% hypertension and 26.4% had ischemic heart disease. Pre-existing CKD was identified in 35.8%; 16.4% CKD stage 3a, 13.4% CKD stage 3b, 5.5% CKD 4 and 1 patient CKD 5. The majority (76.1%) underwent single toe amputations. Surgery was performed under loco-regional anaesthesia in 90% of patients, mostly in view of lower limb ulcers (64.7%) or gangrene (29.4%). A cohort of 54 (26.9%) patients received iodine based contrast within 7 days of procedure, including those who underwent bypass surgery (8%) and endarterectomy (4%). The incidence of AKI after minor lower limb amputations using AKIN criteria was 18.9%. An additional 12 patients were identified using KDIGO criteria (24.9%), however KDIGO criteria could only be applied for 123 patients as the rest did not have a day 7 serum creatinine. Most developed stage 1 AKI (18.4%), one patient developed stage 2 AKI and none developed stage 3 AKI using AKIN criteria. Only 1 patient needed temporary haemodialysis having developed AKI after day 3 post-operatively fulfilling KDIGO but not AKIN criteria. Recovery of kidney function occurred in all patients. All-cause mortality at 30 days, 60 days and 18 months (end of follow-up) was 2.0%, 5.5% and 19.9% respectively. None of the deaths were directly related to the AKI-amputation event. Patients who developed AKI, compared to those who did not, were more likely to have an eGFR &amp;lt;45ml/min/1.73 m2 at the time of procedure (39.5% vs. 14.7%, p = 0.001). They were significantly older (73.0 ±10.4 vs. 68.5 ±11.8 years, p = 0.033), and more likely to have underlying chronic obstructive pulmonary disease (COPD) (28.9% vs. 13.5% p = 0.028). Use of loop and/or thiazide diuretics (68.4% vs. 49.1%, p = 0.049), fluoroquinolones (71.1% vs. 52.8% p = 0.047) and/or carbapenems (10.5% vs. 2.5%, p = 0.043) was also more frequent in this group. Use of iodine based contrast within 7 days of procedure did not effect incidence of AKI. Hospital length of stay and all-cause mortality were not significantly higher in patients with AKI. An eGFR &amp;lt;45ml/min/1.73 m2 was established as a strong independent predictor for the development of AKI (odds ratio [OR] 3.24, confidence interval [CI]: 1.40–7.52, p = 0.006), as were use of fluoroquinolones (OR: 3.19, CI: 1.30–7.82, p = 0.012) and day 1 C-reactive protein (CRP) (OR: 1.01, CI: 1.00–1.01, p = 0.009). Cumulative survival censored at the end of follow-up was not significantly lower in patients who developed AKI (log rank: 0.45, p = 0.50). Conclusion In our study, 18.9% of patients developed AKI after minor lower limb amputations using AKIN criteria. One patient required acute haemodialysis. Age, COPD, diuretics, fluoroquinolones and carbapenems were associated with increased incidence of AKI. An eGFR &amp;lt;45ml/min/1.73 m2, day 1 CRP and fluoroquinolone use were independent risk factors for the development of AKI. In this small patient cohort, AKI was not associated with higher all-cause mortality, and none of the deaths were directly related to the AKI-amputation event.

Association between immune checkpoint inhibitor-induced myocarditis and concomitant use of thiazide diuretics.

Although an association has been reported between diuretics and myocarditis, it is unclear whether the risk of immune checkpoint inhibitor (ICI)-induced myocarditis is affected by concomitant diuretics. Thus, the aim of this work was to evaluate the impact of concomitant diuretics on ICI-induced myocarditis. This cross-sectional study used disproportionality analysis and a pharmacovigilance database to assess the risk of myocarditis with various diuretics in patients receiving ICIs via the analysis of data entered into the VigiBase database through December 2022. Multiple logistic regression analysis was performed to identify risk factors for myocarditis in patients who received ICIs. A total of 90 611 patients who received ICIs, including 975 cases of myocarditis, were included as the eligible dataset. A disproportionality in myocarditis was observed for loop diuretic use (reporting odds ratio 1.47, 95% confidence interval [CI] 1.02-2.04, P = .03) and thiazide use (reporting odds ratio 1.76, 95% CI 1.20-2.50, P < .01) in patients who received ICIs. The results of the multiple logistic regression analysis showed that the use of thiazides (odds ratio 1.67, 95% CI 1.15-2.34, P < .01) was associated with an increased risk of myocarditis in patients who received ICIs. Our findings may help to predict the risk of myocarditis in patients receiving ICIs.

CO12 Evaluation of Hyponatremia Risk Among Geriatric Patients Exposed to Selective Serotonin Reuptake Inhibitors (SSRIS) and Thiazide Diuretics

Hyponatremia is a common electrolyte disorder among the elderly that can cause serious adverse effects. The purpose of this study was to assess the risk of hyponatremia and the concurrent use of selective serotonin reuptake inhibitors (SSRIs) and thiazide diuretics in a geriatric population.

PREVALENCE AND CLINICAL CORRELATES OF HYPOTENSIVE EPISODES AMONG OLDER HYPERTENSIVE ADULTS UNDERGOING 24-H AMBULATORY BLOOD PRESSURE MONITORING

Objective: Older adults have increased susceptibility to hypotension. Hypotensive episodes have a negative prognostic impact at old age, being associated with adverse events such as syncope, falls and injuries, which impair quality of life and functional autonomy. 24-hour ambulatory blood pressure monitoring (ABPM) is a useful diagnostic tool to detect hypotension, although it is rarely used for this purpose. The present study aimed at assessing the prevalence and the clinical variables associated with hypotensive episodes on ABPM among older hypertensive adults. Design and method: prospective observational study involving hypertensive patients aged 75 or older evaluated at two outpatient clinics of Careggi Hospital, Florence, Italy. All participants underwent a comprehensive geriatric assessment, office blood pressure measurement and ABPM. Hypotensive episodes were defined as single daytime systolic blood pressure (SBP) measures &lt;90 mmHg. Clinical variables associated with hypotensive episodes were investigated using multivariable logistic regression. Results: Among 123 participants (mean age 81 years, 59% female), the 16% showed hypotensive episodes on ABPM. Patients with hypotensive episodes were older (84±5 vs 81±4 years, p = 0.002), had a higher prevalence of dementia (50% vs 26%, p = 0.034) and received a higher number of daily medications (8[6-10] vs 6 [5-9], p = 0.036). Moreover, they showed lower 24h-SBP (139±15 vs 149±15, p = 0.008), daytime SBP (141±15 vs 151±15, p = 0.005) and night-time SBP (129±18 vs 140±20, p = 0.005) and a higher prevalence of white coat effect (30% vs 12%, p = 0.034). At multivariable analysis, hypotensive episodes were associated with use of angiotensin-receptor blockers (ARBs, OR 24.325, p = 0.002), independently of age, sex, dementia, 24h-SBP and number of medications. By contrast, use of ACE-inhibitors (OR 0.719, p = 0.013) and thiazide diuretics (OR 0.978, p = 0.048) were inversely associated with hypotension on ABPM. Conclusions: Hypotensive episodes are a common finding in older adults undergoing ABPM. Hypotensive episodes more frequently occur in patients with lower SBP and white coat effect and are independently associated with ARBs use. ACE-inhibitors and thiazides are inversely associated with hypotensive episodes on ABPM.

Hyponatraemia and changes in natraemia during hospitalization for acute heart failure and associations with in-hospital and long-term outcomes - from the ESC HFA EORP Heart Failure Long-Term Registry.

To comprehensively assess hyponatraemia in acute heart failure (AHF) regarding prevalence, associations, hospital course, and post-discharge outcomes. Of 8,298 patients in the ESC-HF Long-Term Registry hospitalized for AHF with any ejection fraction, 20% presented with hyponatraemia (serum sodium <135 mmol/L). Independent predictors included lower systolic blood pressure, estimated glomerular filtration rate (eGFR) and haemoglobin, along with diabetes, hepatic disease, use of thiazide diuretics, mineralocorticoid receptor antagonists, digoxin, higher doses of loop diuretics, and non-use of angiotensin-converting-enzyme inhibitors/angiotensin receptor blockers and beta-blockers. In-hospital death occurred in 3.3%. The prevalence of hyponatraemia and in-hospital mortality with different combinations were: 9% hyponatraemia both at admission and discharge (hyponatraemia Yes/Yes, in-hospital mortality 6.9%), 11% Yes/No (in-hospital mortality 4.9%), 8% No/Yes (in-hospital mortality 4.7%), and 72% No/No (in-hospital mortality 2.4%). Correction of hyponatraemia was associated with improvement in eGFR. In-hospital development of hyponatraemia was associated with greater diuretic use and worsening eGFR but also more effective decongestion. Among hospital survivors, 12-month mortality was 19% and adjusted hazard ratios were for hyponatraemia Yes/Yes 1.60 (1.35-1.89), Yes/No 1.35 (1.14-1.59), and No/Yes 1.18 (0.96-1.45). For death or HF hospitalization they were 1.38 (1.21-1.58), 1.17 (1.02-1.33), and 1.09 (0.93-1.27), respectively. Among patients with AHF, 20% had hyponatraemia at admission, which was associated with more advanced HF and normalized in half of patients during hospitalization. Admission hyponatraemia (possibly dilutional), especially if it did not resolve, was associated with worse in-hospital and post-discharge outcomes. Hyponatraemia developing during hospitalization (possibly depletional) was associated with lower risk. This article is protected by copyright. All rights reserved.

Hyponatremia in patients with arterial hypertension: pathophysiology and management.

Sodium is the main cation in the extracellular space. In physiological conditions, sodium concentration in plasma is 135-145 mmol/l. The kidneys play the most important role in the regulation of sodium homeostasis. In recent years, a significant role of glycosaminoglycans, localized mainly in the subcutaneous tissue, and the role of glycocalyx on the surface of vascular endothelial cells, have been documented in the regulation of sodium metabolism. Hyponatremia is defined by a plasma sodium concentration lower than 135 mmol/l. Hyponatremia significantly worsens the prognosis of patients with different chronic diseases. In patients with arterial hypertension, the risk of hyponatremia is 1.5 times higher than in the general population. One of the causes of hyponatremia in patients with arterial hypertension is the use of thiazide or thiazide-like diuretics. The symptoms of hyponatremia are caused mainly by the swelling of cells in the central nervous system. Treatment of hyponatremia depends on the degree and duration (acute or chronic) of hyponatremia as well as presence of clinical symptoms. Too rapid correction of hyponatremia might result in a potentially fatal osmotic demyelinating syndrome. In the present review paper, pathophysiology and management of hyponatremia in patients with arterial hypertension are discussed.