Calcium Channel Blocker Treatment Research Articles

Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone

Pharmacogenetic variants are associated with clinical outcomes during Calcium Channel Blocker (CCB) treatment, yet whether the effects are modified by genetically predicted clinical risk factors is unknown. We analyzed 32,000 UK Biobank participants treated with dihydropiridine CCBs (mean 5.9 years), including 23 pharmacogenetic variants, and calculated polygenic scores for systolic and diastolic blood pressures, body fat mass, and other patient characteristics. Outcomes included treatment discontinuation and heart failure. Pharmacogenetic variant rs10898815-A (NUMA1) increased discontinuation rates, highest in those with high polygenic scores for fat mass. The RYR3 variant rs877087 T-allele alone modestly increased heart failure risks versus non-carriers (HR:1.13, p = 0.02); in patients with high polygenic scores for fat mass, lean mass, and lipoprotein A, risks were substantially elevated (HR:1.55, p = 4 × 10−5). Incorporating polygenic scores for adiposity and lipoprotein A may improve risk estimates of key clinical outcomes in CCB treatment such as treatment discontinuation and heart failure, compared to pharmacogenetic variants alone.

The evaluation of the effect of long-term antihypertensive drug usage on bone density with dental volumetric tomography.

HT is a systemic disease that presents with persistent high blood pressure, which has become an important health problem due to its cause of serious complications and high prevalence in the community. Aim: This study aims to examine the bone mineral density (BMD) of male patients using different groups of antihypertensive drugs for long terms with dental volumetric tomography. The study was carried out using the data of patients who applied to the Dicle University Faculty of Dentistry and underwent the Dental Volumetric Tomography (DVT) scan for any reason. The patients included in the study were divided into 4 groups according to their antihypertensive use; Group 1: 60 patients who never used hypertensive medication before, Group 2: 60 patients who received Calcium Channel Blocker treatment for over 5 years, Group 3: 60 patients who received Beta Blocker treatment for over 5 years, Group 4: 60 patients who received ACE inhibitor treatment for over 5 years. Radiomorphometric measurements were made on the DVT data and the DVT-Mandibular Index Inferior, DVT-Cortical Index, Hounsfield Unit-Cortical and Hounsfield Unit-Spongios values were calculated. The Kruskal-Wallis test, the Mann Whitney test with Bonferroni correction, the One-Way ANOVA and Post-Hoc Tukey test were used in the study. A significant increase in DVT-CI and a significant decrease in HU-CORTIKAL, HU-SPONGIOS and DVT-MII values were observed in the patients using Calcium Channel Blocker medication. These findings pointed to osteoporosis. In addition, no statistically significant difference in the use of antihypertensive drugs in the Beta Blocker and ACE Inhibitor groups compared to the Control Group were found. The long term use of Calcium Channel Blocker group antihypertensive drugs should be considered as a risk factor for osteoporosis in men. Key words:Antihypertensive drug, Osteoporosis, Radiomorphometric index, Mandible, Dental volumetric tomography, Bone mineral density.

Calcium channel blockers and clinical outcomes in patients with continuous-flow left ventricular assist devices.

Current guidelines suggest calcium channel blockers (CCBs) as the second or third option for blood pressure management in patients with left ventricular assist device (LVAD). However, the clinical outcomes of patients with LVAD who receive CCBs remain unclear. Our study aims to analyse the association of CCBs with clinical outcomes in patients after LVAD implantation. This is a retrospective analysis based on the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) from 2006 to 2017, and adult patients who were alive with LVAD and CCB treatment information at 6months after implantation were included. Among 10717 patients, 1369 received CCBs 6months after implantation, and there was an increasing trend of CCB use after LVAD. Patients receiving CCB therapy at 6months had a similar 5year survival rate to those not receiving CCB [49.6%, 95% confidence interval (CI): 47.5-51.7% vs. 51.1%, 95% CI: 45.3-56.7%]. In both Cox and competing risk regressions after adjusting for confounding factors, CCB treatment at 6months after implantation was not associated with long-term mortality [hazard ratio (HR): 1.03, 95% CI: 0.91-1.17, P=0.624 and subdistribution HR (SHR): 1.07, 95% CI: 0.95-1.22, P=0.260]. Consistently, in time-varying models, CCB treatment was not linked to long-term mortality (HR: 0.97, 95% CI: 0.87-1.09, P=0.682 and SHR: 1.05, 95% CI: 0.94-1.18, P=0.359). This null association remained in subgroup analysis according to device strategy and propensity-matching analyses. Neurological dysfunction, stroke, bleeding, rehospitalization, and renal dysfunction were more likely to occur among those with CCB when compared with those without CCB treatment. In patients with LVAD, CCB therapy fails to show benefits in long-term survival and is associated with increased incidences of neurological dysfunction, bleeding, renal dysfunction, and rehospitalization.

An association between calcium channel blocker and breast cancer in patients with hypertension: A case-control study

Hypertension is a common disease in clinical practice. Calcium channel blocker (CCB) is an effective antihypertensive agent. There is inconsistent data of an association of CCB and breast cancer in literatures particularly in breast cancer cytology. This study aimed to evaluate this association by a case-control design. The inclusion criteria were adult patients with an age of 18 years or over, diagnosed as hypertension, with a result of mammogram. Those who were pregnant, had no pathological results, or had breast mass prior to diagnosis of hypertension were excluded. Cases defined if the pathological report of any types of breast cancer, while controls were those with benign breast mass. Factors associated with breast cancer were calculated by logistic regression analysis. There were 299 patients met the study criteria. Of those, 100 patients (33.4 %) were in the case group or breast cancer group. There were three factors independently associated with breast cancer. CCB treatment had adjusted odds ratio of 2.25 (95 % confidence interval of 1.36, 3.77), while age of 50 years old or over and hormonal therapy also independently associated with breast cancer with adjusted odds ratios of 3.41 and 2.91, respectively. The CCB group had significantly higher proportion of ductal breast cancer than those who did not take CCB (42.5 % vs 23.8 %, p < 0.001). CCB treatment may be associated with breast cancer especially ductal carcinoma in this study population.

A pilot pharmacogenetic study of calcium channel blocker treatment of bipolar mania

Common genetic variants located in calcium channel genes are important markers of genetic susceptibility for bipolar disorder (BD). Previous clinical trials with Calcium Channel Blocker (CCB) medication improved mood stability for some BD patients. We hypothesize that manic patients who carried calcium channel risk variants would differentially benefit from treatment with CCBs. In this pilot study, 50 BD patients (Chinese: 39; US: 11) who were hospitalized for manic episodes were given add-on CCB treatment. We determined genotypes for each patient. There was a significant decrease in the Young Mania Rating Scale (YMRS) after add-on medication treatment. Of note, two intronic variants of the Calcium Voltage-Gated Channel Subunit Alpha1 B (CACNA1B) were associated with treatment outcomes for manic patients: rs2739258 and rs2739260. BD rs2739258/rs2739260 AG-allele carriers had a better treatment response with add-on CCB than those carrying the AA or GG genotypes by survival analysis. Although these findings did not pass multiple testing correction, this study suggests that single-nucleotide polymorphisms (SNPs) residing in calcium channel genes could be predictors for response to add-on CCB treatment of bipolar mania patients, and that calcium channel genes may be involved in treatment responses for BD.

Ivabradine for controlling heart rate in permanent atrial fibrillation: A translational clinical trial

Pharmacological options for rate control in atrial fibrillation are scarce. Ivabradine was postulated to reduce the ventricular rate in this setting. The objectives of this study were to evaluate the mechanism of inhibition of atrioventricular conduction produced by ivabradine and to determine its efficacy and safety in atrial fibrillation. The effects of ivabradine on atrioventricular node and ventricular cells were studied by invitro whole-cell patch-clamp experiments and mathematical simulation of human action potentials. In parallel, a multicenter, randomized, open-label, phase III clinical trial compared ivabradine with digoxin for uncontrolled permanent atrial fibrillation despite β-blocker or calcium channel blocker treatment. Ivabradine 1 μM inhibited "funny" current and rapidly activating delayed rectifier potassium channel current by 28.9% and 22.8%, respectively (P < .05). The sodium channel current and L-type calcium channel current were reduced only at 10 μM. Ivabradine slowed the firing frequency of a modeled human atrioventricular node action potential by 10.6% and induced a minimal prolongation of ventricular action potential. Thirty-five (51.5%) patients were randomized to ivabradine and 33 (49.5%) to digoxin. The mean daytime heart rate decreased by 11.6 beats/min (-11.5%) in the ivabradine arm (P = .02) vs 19.6 (-20.6%) in the digoxin arm (P < .001), although the noninferiority margin of efficacy was not met (Z = -1.95; P = .97). The primary safety end point occurred in 3 patients (8.6%) on ivabradine and in 8 (24.2%) on digoxin (P = .10). Ivabradine produced a moderate rate reduction in patients with permanent atrial fibrillation. The inhibition of funny current in the atrioventricular node seems to be the main mechanism responsible for this reduction. Compared with digoxin, ivabradine was less effective, was better tolerated, and had a similar rate of serious adverse events.

The risk of second primary malignancies in colorectal cancer patients using calcium channel blockers

Calcium channel blockers are among the most commonly used agents in the treatment of cardiovascular diseases. There are several known side-effects associated with their long-term use, whereas other potential adverse effects are yet to be proven. This study aims to evaluate the association between calcium channel blockers exposure and the incidence of second primary malignancy. We established a cohort of 1401 patients with colorectal cancer diagnosed in our institution between January 2003 and December 2016. Patients were followed-up until December 2020. The tumor characteristics and basic clinical data including medication information were obtained from the hospital information system database. Second malignancy was detected in 301 patients (21.5%), and occurred in 27.8% of patients who used calcium channel blockers compared to only 19.9% among non-users. Their use was associated with an increased incidence of bladder cancer in particular. Subanalysis of patients with second malignancy displayed a higher proportion of right-sided colon cancer compared to rectal carcinoma in non-users. Survival analysis revealed significantly better outcomes in early-stage colorectal cancer patients without a history of calcium channel blockers treatment or second primary malignancy.

Calcium-channel blockers: Clinical outcome associations with reported pharmacogenetics variants in 32 000 patients.

Pharmacogenetic variants impact dihydropyridine calcium-channel blockers (dCCBs; e.g., amlodipine) treatment efficacy, yet evidence on clinical outcomes in routine primary care is limited. Reported associations in pharmacogenomics knowledge base PharmGKB have weak supporting evidence. We aimed to estimate associations between reported pharmacogenetic variants and incident adverse events in a community-based cohort prescribed dCCB. We analysed up to 32 360 UK Biobank participants prescribed dCCB in primary care (from UK general practices, 1990-2017). We investigated 23 genetic variants. Outcomes were incident diagnosis of coronary heart disease, heart failure (HF), chronic kidney disease, oedema and switching antihypertensive medication. Participants were aged 40-79 years at first dCCB prescription. Carriers of rs877087 T allele in RYR3 had increased risk of hazard ratio (HF 1.13: 95% confidence interval 1.02 to 1.25, P= .02). Although nonsignificant after multiple testing correction, the association is consistent with prior evidence. We estimated that if rs877087 T allele could experience the same treatment effect as noncarriers, the incidence of HF in patients prescribed dCCB would reduce by 9.2% (95% confidence interval 3.1 to 15.4). In patients with a history of heart disease prior to dCCB (n =2296), rs877087 homozygotes had increased risk of new coronary heart disease or HF compared to CC variant. rs10898815 in NUMA1 and rs776746 in CYP3A5 increased likelihood of switching to an alternative antihypertensive. The remaining variants were not strongly or consistently associated with studied outcomes. Patients with common genetic variants in NUMA1, CYP3A5 and RYR3 had increased adverse clinical outcomes. Work is needed to establish whether outcomes of dCCB prescribing could be improved by prior knowledge of pharmacogenetics variants supported by clinical evidence of association with adverse events.

The effect of calcium channel blocker (CCB) treatment on retinal and choroidal vessels in a group of hypertensive patients

ABSTRACT Purpose The present study was designed to observe the vasoreactivity in retina and choroid after calcium channel blocker (CCB) treatment in a group of hypertensive patients. Method The study was based on 56 hypertensive patients (56 eyes) and 56 control subjects (56 eyes). Choroidal scans and the measurement of peripapillary retinal vessel diameters was performed at baseline and optical coherence tomography (OCT) scans were also performed at first month . Subfoveal choroidal thickness (SFCT) and the diameters of superior temporal artery (STA), inferior temporal artery (ITA), superior temporal vein (STV), inferior temporal vein (ITV) were compared between the groups. Results The baseline diameters of the STA, ITA were significantly decreased in the patient group compared with the control group (all p < .05). There was a significant increase at first month after the CCB treatment in comparison to baseline measurements (all p < .05). When compared with the controls, the diameter of venules showed a decrease at baseline but was not significant. After the treatment, the diameters of venules were insignificantly increased compared with baseline measurements (p = .178 and p = .275) and there were also no significant differences between the control group and the patient group in first month (all p > .05). The average choroidal thickness measurements of the hypertensive group was lower than the control group (p = .404) and there was a tendency to increase after the treatment (p = .055). Conclusion This study demonstrates that, treatment with CCB seems to improve retinal arteries and has almost no affect on the choroidal thickness in newly diagnosed hypertensive patients.

Calcium channel blockers improve the prognosis of patients with intrahepatic cholangiocarcinoma after resection.

Intrahepatic cholangiocarcinoma is the second most common primary cancer of the liver. It is highly malignant and its prognosis is very poor. Although there have been various reports on the effects of calcium channel blockers on cancer, the effects of calcium channel blockers on intrahepatic cholangiocarcinoma have not been reported so far. Seventy-nine patients diagnosed with intrahepatic cholangiocarcinoma by hepatectomy between January 2002 and May 2019 were retrospectively evaluated. We compared prognosis and time to recurrence between patients treated with calcium channel blockers (CCBs) (n = 29) and those not treated with CCBs (n = 50). Propensity score matching reduced confounding biases and yielded 25 matched patient pairs. Survival between groups was compared using Kaplan-Meier analyses, logrank tests, and Cox proportional hazard regression models. Overall survival and recurrence-free survival of the CCBs group were significantly longer than those of the non-CCBs group OS in the original cohort and matched cohort (98months vs 45months, p = 0.010; 96months vs 22months, p = 0.020, respectively). Multivariate analyses showed that CCBs treatment was independently associated with overall survival (HR, 0.37; 95% CI 0.16-0.85; p = 0.019) and recurrence-free survival (HR, 0.39; 95% CI 0.17-0.90; p = 0.020) in the original cohort and matched cohort, respectively. CCBs treatment might improve prognosis of patients with intrahepatic cholangiocarcinoma.

Positive association between calcium channel blocker treatment and persistent type II endoleak.

Type II endoleaks are the most common complication occurring after endovascular abdominal aortic aneurysm repair (EVAR). The aims of our study were to evaluate the impact of persistent type II endoleak on sac dynamics post-EVAR, and to study the association between non-anatomical factors including polymorphisms associated with abdominal aortic aneurysm (AAA) and persistent type II endoleak. The cohort comprises 210 patients undergoing EVAR between January 2010 and December 2018. A persistent type II endoleak was defined as any type II endoleak lasting longer than six months and included also a type II endoleak diagnosed after six months or more post-EVAR during the 36-month follow-up period confirmed with CT-angiography. Anteroposterior AAA maximum diameter and AAA volume were measured pre-EVAR and 36 months post-EVAR using CT-angiographic pictures. Sac progression was defined as at least 5 mm increase, sac regression as at least 5 mm decrease in the sac diameter in relation to the preprocedural diameter. Sociodemographic information, comorbidities, treatment, laboratory parameters, selected anatomical and genetic factors were all analyzed to determine their impact on persistent type II endoleak. The adjustments included age, hypertension, diabetes mellitus, dyslipidemia, sex, smoking in multivariate analyses. When postprocedural diameter and volume were evaluated, adjustments included also preprocedural diameter/volume. After exclusion, 178 patients with mean age 72.4±7.60 years remained for analysis. Persistent type II endoleak was found in 27.5% of patients (N.=49) and 2.94-times increased risk of sac progression in multivariate analysis (P=0.033). In multivariate analysis, AAA diameter in patients with persistent type II endoleak was 4.31 mm greater than in patients without (B=4.31; P=0.014); and its presence was also associated with 22.0 cm3 greater sac volume (B=22.0; P=0.034) compared to patients without persistent type II endoleak. Treatment with calcium channel blockers increased risk of persistent type II endoleak 2.11-times in multivariate analysis (OR=2.11; 95% CI: 1.05-4.25; P=0.037). No association between persistent type II endoleak and selected polymorphisms associated with AAA and other observed factors were found. Risk of persistent type II endoleak was more than doubled in patients taking calcium channel blockers. Patients with persistent type II endoleak had greater anteroposterior sac diameter and sac volume compared to patients without persistent type II endoleak.

Comparative peripheral edema for dihydropyridines calcium channel blockers treatment: A systematic review and network meta-analysis.

Dihydropyridine calcium channel blockers (DHPCCBs) are widely used to treat hypertension and chronic coronary artery disease. One common adverse effect of DHPCCBs is peripheral edema, particularly of the lower limbs. The side effect could lead to dose reduction or discontinuation of the medication. The combination of DHPCCBs and renin‐angiotensin system blockers has shown to reduce the risk of DHPCCBs‐associated peripheral edema compared with DHPCCBs monotherapy. We performed the current systematic review and network meta‐analysis of randomized controlled trials (RCTs) to estimate the rate of peripheral edema with DHPCCBs as a class and with individual DHPCCBs and the ranking of the reduction of peripheral edema. The effects of renin‐angiotensin system blockers on DHPCCBs network meta‐analysis were created to analyze the ranking of the reduction of peripheral edema. A total of 3312 publications were identified and 71 studies with 56,283 patients were included. Nifedipine ranked highest in inducing peripheral edema (SUCRA 81.8%) and lacidipine (SUCRA 12.8%) ranked the least. All DHPCCBs except lacidipine resulted in higher relative risk (RR) of peripheral edema compared with placebo. Nifedipine plus angiotensin receptor blocker (SUCRA: 92.3%) did not mitigate peripheral edema and amlodipine plus angiotensin‐converting enzyme inhibitors (SUCRA: 16%) reduced peripheral edema the most. Nifedipine ranked the highest and lacidipine ranked the lowest amongst DHPCCBs for developing peripheral edema when used for cardiovascular indications. The second or higher generation of DHPCCBs combination with ACEIs or ARBs or diuretics lowered the chance of peripheral edema development compared to single DHPCCB treatment.

Effects of dibenzylbutyrolactone lignans arctigenin and trachelogenin on the motility of isolated rat ileum

Dibenzylbutyrolactone-type lignans are phenolic compounds of medical importance. The purpose of the study was to determine the effects of two such lignans, arctigenin and trachelogenin on the motility of isolated rat ileum and obtain indications on their mechanism of action. They were isolated from Arctium lappa and Cirsium arvense, respectively, which have been used traditionally to treat gastrointestinal disorders. 1–1.5 cm long segments of distal ileum were obtained from adult male Wistar rats. The intestinal segments were suspended vertically in a well-aerated organ-bath according to Magnus mounting method. The intestinal motility was monitored for 30 min before treatment to obtain the baseline, followed by treatment with 1 µM, 10 µM, 20 µM and 40 µM concentrations of arctigenin and 0.5 µM, 1 µM, 10 µM and 20 µM of trachelogenin concentrations. The amplitude, tone, and period of spontaneous contractions were measured after 15 and 30 min of treatment. To investigate their mechanism of action, cholinergic, glutamatergic, adrenergic antagonists and compounds inhibiting nitric oxide synthase and L-type calcium channels were also tested. Arctigenin and trachelogenin decreased the frequency of contractions in a dose-dependent manner. At the concentration of 20 µM and 40 µM of trachelogenin and arctigenin, respectively, there was a marked alteration in spontaneous contraction pattern with an observable increase in the period time. This activity was comparable to 0.5 µM nifedipine (L-type calcium channel blocker) treatment. Our results demonstrate relaxant effect of arctigenin and trachelogenin on the ileum motility that may be mediated by L-type calcium ion channel blockade.

Questioning the renoprotective role of L-type calcium channel blockers in chronic kidney disease using physiological modeling.

Chronic kidney disease (CKD) is characterized by the progressive functional loss of nephrons and hypertension (HTN). Some antihypertensive regimens attenuate the progression of CKD (blockers of the renin-angiotensin system). Although studies have suggested that calcium channel blocker (CCB) therapy mitigates the decline in renal function in humans with essential HTN, there are few long-term clinical studies that have determined the impact of CCBs in patients with hypertensive CKD. Dihydropyridine (DHP) or L-type CCBs preferentially vasodilate the afferent arteriole and have been associated with glomerular HTN and increases in proteinuria in animal models with low renal function. Small clinical studies in vulnerable populations with renal disease such as African Americans, children, and diabetics have also suggested that DHP CCBs exacerbate glomerular injury, which questions the renoprotective effect of this class of antihypertensive drug. We used an established integrative mathematical model of human physiology, HumMod, to test the hypothesis that DHP CCB therapy exacerbates pressure-induced glomerular injury in hypertensive CKD. Over a simulation of 3 yr, CCB therapy reduced mean blood pressure by 14-16 mmHg in HTN both with and without CKD. Both impaired tubuloglomerular feedback and low baseline renal function exacerbated glomerular pressure, glomerulosclerosis, and the decline in renal function during L-type CCB treatment. However, simulating CCB therapy that inhibited both L- and T-type calcium channels increased efferent arteriolar vasodilation and alleviated glomerular damage. These simulations support the evidence that DHP (L-type) CCBs potentiate glomerular HTN during CKD and suggest that T/L-type CCBs are valuable in proteinuric renal disease treatment.NEW & NOTEWORTHY Our physiological model replicates clinical trial results and provides unique insights into possible mechanisms that play a role in glomerular injury and hypertensive kidney disease progression during chronic CCB therapy. Specifically, these simulations predict the temporal changes in renal function with CCB treatment and demonstrate important roles for tubuloglomerular feedback and efferent arteriolar conductance in the control of chronic kidney disease progression.

Effects of angiotensin II receptor blockers on serum potassium level and hyperkalemia risk: retrospective single-centre analysis

ObjectiveTo examine the effect of angiotensin II receptor blocker (ARB) treatment on serum potassium level and hyperkalaemia risk in a clinical setting with inpatients and outpatients using calcium channel blockers...

Correlations Among Visit-to-Visit Blood Pressure Variability and Treatment With Antihypertensive Medication With Long-Term Adverse Outcomes in a Large Veteran Cohort.

Blood pressure variability (BPV) is associated with adverse events (AEs) independently of hypertension. It has been suggested that calcium channel blockers (CCBs) may reduce BPV, and thus be particularly valuable in hypertensives with high BPV. We sought to investigate how CCB affect BPV progression and whether long-term adverse effects of BPV differ after CCB treatment than after treatment with other antihypertensives. We retrospectively analyzed 25,268 US veterans who had been followed for 3 years without hypertensive therapy, started on a single class of antihypertensive agents (thiazides, CCBs, ACE inhibitors, or beta blockers [BBs]), treated for 6 years, and then followed for 3 additional years. BPV was calculated as SD of systolic or diastolic blood pressures from at least 10 measurements over each 3-year period. A combined AE endpoint included hospitalization, coronary artery bypass grafting, carotid endarterectomy, angioplasty, amputation, arteriovenous fistula creation, and mortality was assessed in years 9-12. Post-medication high BPV and BB or thiazide use were associated with increased AE risk. Medication type also affected mean post-medication BPV. The effects of medications except for BBs on AE and mortality was independent of the patient BPV. The possible deleterious effects of thiazides should be considered within the context of the study population, who were mostly male and received only a single class of hypertensives. While CCB may ameliorate BPV over time, this study does not support choosing CCB over other agents specifically to lessen BPV-associated risk.

Beneficial effects of exercise training on physical performance in patients with vasospastic angina

AimsIn vasospastic angina (VSA), coronary vasomotion abnormalities could develop not only in epicardial coronary arteries but also in coronary microvessels, where calcium channel blockers (CCBs) have limited efficacy. However, efficacy of exercise training for VSA remains to be elucidated. We thus aimed to examine whether vasodilator capacity of coronary microvessels is impaired in VSA patients, and if so, whether exercise exerts beneficial effects on the top of CCBs. MethodsWe performed 2 clinical protocols. In the protocol 1, we measured myocardial blood flow (MBF) using adenosine-stress dynamic computed tomography perfusion (CTP) in 38 consecutive VSA patients and 17 non-VSA controls. In the protocol 2, we conducted randomized controlled trial, where 20 VSA patients were randomly assigned to either 3-month exercise training group (Exercise group) or Non-Exercise group (n= 10 each). ResultsIn the protocol 1, MBF on CTP was significantly decreased in the VSA group compared with the Non-VSA group (138 ± 6 vs 166 ± 10 ml/100 g/min, P = 0.02). In the protocol 2, exercise capacity was significantly increased in the Exercise group than in the Non-Exercise group (11.5 ± 0.5 to 15.4 ± 1.8 vs 12.6 ± 0.7 to 14.0 ± 0.8 ml/min/kg, P < 0.01). MBF was also significantly improved after 3 months only in the Exercise group (Exercise group, 145 ± 12 to 172 ± 8 ml/100 g/min, P < 0.04; Non-Exercise group, 143 ± 14 to 167 ± 8 ml/100 g/min, P = 0.11), although there were no significant between-group differences. ConclusionsThese results provide the first evidence that, in VSA patients, exercise training on the top of CCBs treatment may be useful to improve physical performance, although its effect on MBF may be minimal.

P0178COMPARATIVE EFFECTIVENESS OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS AND CALCIUM CHANNEL BLOCKERS IN INDIVIDUALS WITH ADVANCED CHRONIC KIDNEY DISEASE: A NATIONWIDE COHORT STUDY

Abstract Background and Aims There is a lack of data that could help to guide the choice of antihypertensive agents in patients with advanced chronic kidney disease (CKD). We evaluated whether initiating treatment with a renin-angiotensin system inhibitor (RASi) is superior to calcium channel blockers (CCB) in preventing mortality, major adverse cardiovascular events (MACE) or kidney replacement therapy (KRT) in patients with advanced CKD. Method Observational study from the Swedish Renal Register, 2007-2017. We identified all nephrologist-referred patients in Sweden who initiated RASi or CCB treatment and had non-dialysis dependent advanced CKD (eGFR &amp;lt;30 ml/min/1.73m2). The associations between RASi vs CCB initiation, mortality, MACE and KRT were assessed by Cox regression. Analyses were adjusted with propensity score weighting for a wide range of confounders, including demographics, blood pressure, laboratory measures, comorbidities and medications. As a positive control we evaluated new use of the same drugs in patients with CKD G3 (N = 2608; eGFR between 30-60 ml/min/1.73m2). Furthermore subgroup, as-treated and competing risk analyses were performed. Results The propensity-score weighted cohort included 2479 RASi and 2327 CCB initiators who were well-matched for baseline confounders (all standardized differences &amp;lt;0.1). Median follow-up was 4.1 years, with a maximum follow-up of over 10 years. Compared to CCB, initiation of RASi was associated with a similar risk of mortality (adjusted HR 0.94; 95% CI 0.85-1.03) and MACE (0.99; 0.87-1.13), but with a lower risk of KRT (0.87; 0.78-0.98). Results were consistent across subgroups, in as-treated analyses and after accounting for the competing risk of death. In the control cohort of patients with CKD G3, initiation of RASi (versus CCB) was associated with lower KRT risk (adjusted HR 0.67; 0.47-0.96), and similar risk of mortality (0.91; 0.76-1.08) and MACE (1.06; 0.82-1.35). Conclusion Compared with CCB, initiation of RASi in patients with advanced CKD was associated with a lower risk of KRT, but no different risk of mortality or MACE.

SUN-LB121 Nifedipine Worsens Glucose Tolerance in C57BL/6J Mice Exposed to Intermittent Hypoxia

Background: Intermittent hypoxemia (IH), a pathognomonic component of obstructive sleep apnea (OSA), has been independently associated with development of glucose intolerance, insulin resistance, and type 2 diabetes. L-type calcium channel blockers (CCB) influence glucose homeostasis including insulin sensitivity and secretion. To date, the potential impact of the combined effects of L-type CCB and IH on fasting glycemia and glucose tolerance have not been examined. The objective of this study was to determine whether CCB alters glucose metabolism in a murine model of IH. Methods: Adult male C57BL6/J mice (age 19-week-old) were exposed to IH using an automated system with specially-modified cages that oscillated FiO2from 21% to 5.5% at a target rate of 60 events/h during a 12 h (7am – 7pm) light cycle to simulate severe OSA for 5 days. The L-type CCB, nifedipine, or vehicle (polyethleneglycol-400) were administered at a dose of 20mg/kg/day via subcutaneous osmotic pumps (Alzet model 2001). Mice were exposed to IH or intermittent air (IA) with four resulting groups: IA-vehicle (n=12), IH-vehicle (n=16), IA–nifedipine (n=10), and IH–nifedipine (n=13). Fasting glucose, intraperitoneal glucose tolerance test, and insulin levels were obtained after exposures. Results: In the absence of a L-type CCB, IH increased fasting (105.1 vs. 71.2 mg/dL; p<0.001) and 2-hour glucose levels (104.8 vs. 82.0 mg/dL; p=0.003). The area under the glucose tolerance curve (AUC) was also higher with IH than IA in mice treated with vehicle (17896.3 vs.13965.8 mg-min/dL; p<0.001). Although the effects of IH on fasting glucose levels were comparable with and without L-type CCB treatment, the 2-hour glucose levels and the AUCs were substantially different. A statistically significant interaction was noted for the 2-hr glucose levels between IH and treatment with a L-type CCB (IH-CCB: 193.7; IH-V: 122.6; IA-CCB: 103.5; and IA-V: 82.0 mg/dL; p<0.05 for interaction between IH and CCB). Finally, the AUC for IH-CCB treated mice was significantly higher than the AUC for IH-V treated mice (IH-CCB: 30223.1; IH-V: 17896.3. mg-min/dL; p=0.0001) Conclusions: In a murine model of IH, treatment with an L-type CCB exacerbates the deleterious effects of IH on glucose tolerance. Thus, use of CCB in patients with OSA should take into consideration these unfavorable effects particularly in those who are metabolically compromised.

Ankle ulcer as a complication of systemic lupus erythematosus: A case report

Background: In 10-20% of cases, Raynaud’s Phenomenon (RP) is an initial manifestation of underlying connective tissue disease such as systemic lupus erythematosus (SLE), then Raynaud’s Phenomenon on SLE called secondary RP. Case presentation: A 26-year-old female came with pain in the fingers and toes. Pain aggravated by activity and cold temperatures. there are black-coloured changes at the tips of the toes, pale and bluish at bilateral fingertips. History of systemic lupus erythematosus since last 3 months. Physical examination revealed bilateral pale and cyanotic fingers, Black-colored sores on the right lateral malleolus, 1st and 5th toe of the right foot, 2nd and 3rd toes of the left foot. There is tenderness and pitting oedema. Peripheral pulses are not palpable. The antinuclear Antibody (ANA) profile is positive. Multislice computed tomography (MSCT) Angiography of the bilateral lower extremity was performed where there is stenosis proximal right dorsalis pedis artery, stenosis right plantar pedis artery, stenosis 1/3 medial left tibial posterior artery, and stenosis 1/3 distal left tibial anterior artery. The patient was diagnosed with secondary RP because of SLE and we performed debridement of the wound, then treated the patient with calcium channel blocker, prostacyclin analogue, antiplatelet and non-pharmacological treatment included avoiding cold exposure. Symptom resolution and ANA titer reduction are obtained at intervals of two- and six-months post-treatment. Conclusion: RP in this case is a manifestation of systemic lupus erythematous. Ulcer in the lateral malleolus area is a complication of secondary RP.