Prior Cardiovascular Events Research Articles

Long-term treatment persistence and maintained reduction of LDL-cholesterol levels with evolocumab over 30 months: Results from the Spanish cohort of the European prospective HEYMANS study

AimsLimited data exist on low-density lipoprotein-cholesterol (LDL-C) level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. HEYMANS (NCT02770131) is the first multi-country, multicenter, observational study of European patients initiating evolocumab as part of their routine clinical management, based on local reimbursement criteria (overall data recently published). The aim of this analysis is to describe clinical characteristics, baseline and changes in LDL-C levels, treatment patterns and persistence to evolocumab over 30 months in the Spanish cohort using data from the HEYMANS Registry. MethodsHEYMANS was a prospective study of adult patients (≥18 years) who received at least one dose of evolocumab. A total of 1951 patients were enrolled from 12 countries and were followed up for 30 months after evolocumab initiation. Data were collected for 6 months before evolocumab initiation and up to 30 months thereafter. The Spanish cohort included patients who started evolocumab in routine clinical practice from March 2016 to September 2019. Demographic and clinical characteristics, lipid-lowering therapies (LLT), and lipid levels were collected. ResultsIn total, 201 patients were included in the Spanish cohort. Median follow-up (Q1–Q3) was 30.0 (12–30) months. A total of 61.7% of patients were men and the mean (standard deviation) age was 59.5 (10.8) years. Most patients (68.7%) had experienced a prior cardiovascular event, 45.3% had coronary artery disease or stable angina, and 60.2% had a diagnosis of familial hypercholesterolemia. Overall, 57.7% of patients were receiving treatment with statins, most of them with high-intensity statins (85.3%); 45.8% of patients were intolerant to statins, and 26.4% of patients did not receive any LLT. At baseline, median (Q1–Q3) LDL-C levels were 151 (123–197) mg/dL. After 3 months of treatment, baseline LDL-C decreased by 66% to a median of 50 (30–83) mg/dL and these levels were maintained over time, with a median LDL-C of 55 (40–99) mg/dL at 30 months. At months 10–12 of treatment, LDL-C levels<55mg/dL were achieved by 56.3% of patients. LDL-C levels<70mg/dL were achieved by 70.1% of patients, and a lowering of LDL-C levels ≥50% was achieved by 76.8% of patients. The percentage of patients on evolocumab treatment was 95% at 12 months and 93% at 30 months. ConclusionsIn the Spanish cohort in routine clinical practice, evolocumab therapy provided a reduction in LDL-C levels consistent with that reported in previous clinical trials, which was sustained during 30 months of follow-up. Treatment with evolocumab was started at LDL-C levels 50% higher than those recommended by The Spanish Society of Arteriosclerosis and the Therapeutic Positioning Report. The probability of achieving the 2019 ESC/EAS LDL-C goals would improve with combination therapy and also with a lower LDL-C threshold when starting evolocumab. Persistence to evolocumab remained high during follow-up, with a very low percentage of discontinuation (5% at 12 months; 7% at 30 months).

Early biochemical outcomes following neoadjuvant/adjuvant relugolix with stereotactic body radiation therapy for intermediate to high risk prostate cancer.

Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventionally fractionated radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following relugolix and SBRT for intermediate to high prostate cancer. Relugolix was initiated at least 2 months prior to SBRT. Interventions to improve adherence were not utilized. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone ≤ 20 ng/dL. Early PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and ≤ 0.2 ng/mL during the first 4 months post SBRT. Between July 2021 and January 2023, 52 men were treated at Georgetown with relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were African American and 28.8% were obese (BMI ≥30 kg/m2). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were ≥ Grade Group 3. 44 patients were intermediate- and 8 were high-risk. Patients initiated relugolix at a median of 3.6 months prior to SBRT with a median duration of 6.2 total months. 92.3% of patients achieved profound castration during relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively. Relugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. We observed a 96% testosterone suppresion rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients with localized prostate cancer can consistently and successfully follow an oral ADT protocol without daily reminders. Given relugolix's potential benefits over injectable GnRH receptor agonists, its usage may be preferred in specific patient populations (fear of needles, prior cardiovascular events). Future studies should focus on boundaries to adherence in specific underserved populations.

Lipoprotein(a) is associated with recurrent cardiovascular events in patients with coronary artery disease and prediabetes or diabetes.

Elevated lipoprotein(a) [Lp(a)] and diabetes mellitus (DM) are both associated with adverse events in high-risk patients with established coronary artery disease (CAD). Currently, the association between Lp(a) levels and recurrent cardiovascular (CV) events (CVEs) remained undetermined in patients with different glucose status. Therefore, this study aimed to investigate the prognostic significance of Lp(a) levels for recurrent CVEs in high-risk CAD patients who suffered from first CVEs according to different glycemic metabolism. We recruited 5257 consecutive patients with prior CVEs and followed up for recurrent CVEs, including CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. Patients were assigned to low, medium, and high groups according to Lp(a) levels and further stratified by glucose status. During a median 37-month follow-up, 225 (4.28%) recurrent CVEs occurred. High Lp(a) was independently associated with recurrent CVEs [adjusted Hazard Ratio (HR), 1.57; 95% confidence interval (CI) 1.12-2.19; P = 0.008]. When participants were classified according to Lp(a) levels and glycemic status, high Lp(a) levels were associated with an increased risk of recurrent CVEs in pre-DM (adjusted HR, 2.96; 95% CI 1.24-7.05; P = 0.014). Meanwhile, medium and high Lp(a) levels were both associated with an increased risk for recurrent CVEs in DM (adjusted HR, 3.09; 95% CI 1.30-7.34; P = 0.010 and adjusted HR, 3.13, 95% CI 1.30-7.53; P = 0.011, respectively). This study demonstrated that elevated Lp(a) levels were associated with an increased recurrent CVE risk in patients with CAD, particularly among those with pre-DM and DM, indicating that Lp(a) may provide incremental value in risk stratification in this population.

Statin Treatment on Cardiovascular Risk After Retinal Artery Occlusion: A Historical Cohort Study

IntroductionRetinal artery occlusion (RAO) is a major cause of acute visual loss and patients with RAO have an increased risk for subsequent cardiovascular events. However, there is little evidence of whether the use of statins is associated with the prevention of cardiovascular events in patients with RAO. We investigated whether statin treatment in patients with RAO is associated with a lower risk of cardiovascular events.MethodsThis study was a historical cohort study with nested case–control analysis. Using the nationwide health insurance claims database in Korea, we retrospectively established a cohort of newly diagnosed RAO patients without prior cardiovascular events between January 2008 and March 2020. We defined the case group as those who had cardiovascular events (stroke or myocardial infarction) and the control group as RAO patients without primary outcome matched by sex, age, comorbidities, and duration of follow-up (1:2 incidence density sampling). Conditional logistic regression was performed.ResultsAmong 13,843 patients newly diagnosed with RAO, 1030 patients had cardiovascular events (mean follow-up period of 6.4 ± 3.7 years). A total of 957 cases were matched to 1914 controls. Throughout the study period, the proportion of patients taking statin was less than half. Statin treatment after RAO was associated with a low risk of cardiovascular events (adjusted OR, 0.637; 95% CI 0.520–0.780; P < 0.001). A longer duration of statin exposure was associated with a lower cardiovascular risk.ConclusionsIn patients with newly diagnosed RAO, treatment with statins, particularly long-term use, was associated with a low risk of future cardiovascular events.

Signaling Pathways Associated With Prior Cardiovascular Events in Hypertrophic Cardiomyopathy

BackgroundHypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. A subset of patients experience major adverse cardiovascular events (MACEs), including arrhythmias, strokes and heart failure. However, the molecular mechanisms underlying MACEs in HCM are still not well understood. Therefore, we conducted a multicenter case-control study of patients with HCM, comparing those with and without prior histories of MACEs to identify dysregulated signaling pathways through plasma proteomics profiling. MethodsWe performed plasma proteomics profiling of 4986 proteins. We developed a proteomics-based discrimination model in patients enrolled at 1 institution (training set) and externally validated the model in patients enrolled at another institution (test set). We performed pathway analysis of proteins dysregulated in patients with prior MACEs. ResultsA total of 402 patients were included, with 278 in the training set and 124 in the test set. In this cohort, 257 (64%) patients had prior MACEs (172 in the training set and 85 in the test set). Using the proteomics-based model from the training set, the area under the receiver operating characteristic curve was 0.82 (95% confidence interval, 0.75–0.90) in the test set. Patients with prior MACEs demonstrated dysregulation in pathways known to be associated with MACEs (eg, TGF-β) and novel pathways (eg, Ras-MAPK and associated pathways). ConclusionsIn this multicenter study of 402 patients with HCM, we identified both known and novel pathways dysregulated in a subset of patients with more advanced disease.

Low adherence to the Mediterranean diet is associated with increased prevalence and number of atherosclerotic plaques in the ILERVAS cohort

Background and aimsCurrent research on the association between dietary patterns and subclinical atherosclerotic disease (SAD) is still limited, and published results are inconsistent and often consist of small population sizes. We aimed to evaluate the association between the Mediterranean diet (MDiet) and SAD in a large cohort of Mediterranean individuals. MethodsThis was a cross-sectional study that included 8116 subjects from the ILERVAS cohort. The presence of atherosclerotic plaques (AP) was assessed by ultrasound examination. Adherence to the MDiet was assessed using the 14-item Mediterranean Diet Adherence Score (MEDAS). Inclusion criteria were subjects with at least one cardiovascular risk factor. Exclusion criteria were a clinical history of diabetes, chronic kidney disease, or a prior cardiovascular event. Bivariable and multivariable models were performed. ResultsCompared with subjects without SAD, participants with SAD were older and had a higher frequency of smoking habit, hypertension, dyslipidemia, HbA1c and waist circumference. The adjusted multivariable analysis showed that a higher MEDAS was associated with a lower risk of AP (incidence rate ratios [IRR] 0.97, 95% CI [0.96–0.98]; p<0.001). Furthermore, moderate or high adherence to the MDiet was associated with a lower number of AP compared with a low MDiet adherence (IRR 0.90, 95% CI [0.87–0.94]; p<0.001). In both models, female sex was associated with a lower risk of AP. ConclusionsOur findings point to a potentially protective role of MDiet for SAD in a Mediterranean population with low-to-moderate cardiovascular risk. Further research is needed to establish a causal relationship between both variables.

Bempedoic acid as treatment for subjects at cardiovascular risk who are statin-intolerant

ABSTRACT Introduction Atherosclerotic cardiovascular disease is the leading cause of death globally. LDL cholesterol is a key risk factor for cardiovascular disease. The most common group of medicines for lowering LDL cholesterol are the statins, as they reduce the risk of cardiovascular events. However, some subjects are statin-intolerant and remain at high risk. Areas covered CLEAR Outcomes; a phase 3 clinical trial of bempedoic acid, an ATP citrate lyase (ACL) inhibitor, in subjects who do not tolerate statins or are unable to take the recommended dose. It enrolled subjects with prior cardiovascular events (secondary prevention) and at high risk (primary prevention). The primary endpoint was a composite of major adverse cardiovascular events, and this occurred in less subjects in the bempedoic acid than the placebo group. Expert opinion Bempedoic acid is suitable for use as monotherapy in the prevention of cardiovascular events in statin intolerant subjects, and it has a good safety profile in most subjects. However, the effects of bempedoic acid in lowering LDL cholesterol and cardiovascular events are modest. This suggests that more benefits may ensue ifbempedoic acid was used in combination with other lipid lowering agents to cause larger decreases in LDL cholesterol.

Application of EULAR and European Society of Cardiology recommendations with regard to blood pressure and lipid management in antiphospholipid syndrome

BackgroundTo examine blood pressure (BP) and lipid treatment eligibility in antiphospholipid syndrome (APS) according to European Alliance of Associations for Rheumatology (EULAR) and European Society of Cardiology (ESC) recommendations.MethodsSystematic Coronary...

A marginal structural model to estimate the effect of antidepressant medication treatment on major cardiovascular events among people with post-traumatic stress disorder.

Previous evidence on antidepressant medication and cardiovascular disease (CVD) among patients with posttraumatic stress disorder (PTSD) has been inconclusive. We estimated the association between antidepressant medication and CVD by applying a marginal structural model. We analyzed medical utilization records of 27 170 people with PTSD without prior major cardiovascular events in the Korean National Health Insurance Database (NHID). PTSD and CVD were defined in accordance with the recorded ICD-10 diagnostic codes. We acquired information on antidepressant use from the NHID and categorized them by medication type. A composite major adverse cardiovascular events (MACE) outcome was defined as coronary artery disease with revascularization, ischaemic stroke, and/or haemorrhagic stroke. We used inverse probability of treatment weighting to estimate the parameters of a marginal structural discrete-time survival analysis regression model, comparing the resulting estimates to those derived from traditional time-fixed and time-varying Cox proportional hazards regression. We calculated cumulative daily defined doses to test for a dose-response relationship. People exposed to antidepressants showed a higher hazard of MACE [hazard ratio (HR) 1.34, 95% confidence interval (CI) 1.18-1.53]. The estimated effects were strongest for selective serotonin reuptake inhibitors (HR 1.24, 95% CI 1.08-1.44) and TCAs (HR 1.33, 95% CI 1.13-1.56). Exposure to serotonin-norepinephrine reuptake inhibitors did not appear to increase the risk of MACE. People exposed to higher doses of antidepressants showed higher risk of MACE. In a national cohort of people with PTSD, exposure to antidepressant medications increased the risk of MACE in a dose-response fashion.

Effect of Obesity on Clinical Characteristics of Primary Aldosteronism Patients at Diagnosis and Postsurgical Response.

Patients with obesity have an overactivated renin-angiotensin-aldosterone system (RAAS) that is associated with essential hypertension. However, the influence of obesity in primary aldosteronism (PA) is unknown. We analyzed the effect of obesity on the characteristics of PA, and the association between obesity and RAAS components. A retrospective study was conducted of the Spanish PA Registry (SPAIN-ALDO Registry), which included patients with PA seen at 20 tertiary centers between 2018 and 2022. Differences between patients with and without obesity were analyzed. A total of 415 patients were included; 189 (45.5%) with obesity. Median age was 55 years (range, 47.3-65.2 years) and 240 (58.4%) were male. Compared to those without obesity, patients with obesity had higher rates of diabetes mellitus, chronic kidney disease, obstructive apnea syndrome, left ventricular hypertrophy, prior cardiovascular events, higher means of systolic blood pressure, and required more antihypertensive drugs. Patients with PA and obesity also had higher values of serum glucose, glycated hemoglobin A1c, creatinine, uric acid, and triglycerides, and lower levels of high-density lipoprotein cholesterol. Levels of blood aldosterone (PAC) and renin were similar between patients with and without obesity. Body mass index was not correlated with PAC nor renin. The rates of adrenal lesions on imaging studies, as well as the rates of unilateral disease assessed by adrenal vein sampling or I-6β-iodomethyl-19-norcholesterol scintigraphy, were similar between groups. Obesity in PA patients involves a worse cardiometabolic profile, and need for more antihypertensive drugs but similar PAC and renin levels, and rates of adrenal lesions and lateral disease than patients without obesity. However, obesity implicates a lower rate of hypertension cure after adrenalectomy.

Timing of PCSK9i Initiation and Its Relationship with Clinical Outcomes in US Patients with Prior Cardiovascular Events: A Claims Database Analysis

Timing of PCSK9i Initiation and Its Relationship with Clinical Outcomes in US Patients with Prior Cardiovascular Events: A Claims Database Analysis

Bempedoic Acid for Primary Prevention of Cardiovascular Events in Statin-Intolerant Patients

The effects of bempedoic acid on cardiovascular outcomes in statin-intolerant patients without a prior cardiovascular event (primary prevention) have not been fully described. To determine the effects of bempedoic acid on cardiovascular outcomes in primary prevention patients. This masked, randomized clinical trial enrolled 13 970 statin-intolerant patients (enrollment December 2016 to August 2019 at 1250 centers in 32 countries), including 4206 primary prevention patients. Participants were randomized to oral bempedoic acid, 180 mg daily (n = 2100), or matching placebo (n = 2106). The primary efficacy measure was the time from randomization to the first occurrence of any component of a composite of cardiovascular death, nonfatal myocardial infarction (MI), nonfatal stroke, or coronary revascularization. Mean participant age was 68 years, 59% were female, and 66% had diabetes. From a mean baseline of 142.2 mg/dL, compared with placebo, bempedoic acid reduced low-density lipoprotein cholesterol levels by 30.2 mg/dL (21.3%) and high-sensitivity C-reactive protein levels by 0.56 mg/L (21.5%), from a median baseline of 2.4 mg/L. Follow-up for a median of 39.9 months was associated with a significant risk reduction for the primary end point (111 events [5.3%] vs 161 events [7.6%]; adjusted hazard ratio [HR], 0.70 [95% CI, 0.55-0.89]; P = .002) and key secondary end points, including the composite of cardiovascular death, MI, or stroke (83 events [4.0%] vs 134 events [6.4%]; HR, 0.64 [95% CI, 0.48-0.84]; P < .001); MI (29 events [1.4%] vs 47 events [2.2%]; HR, 0.61 [95% CI, 0.39-0.98]); cardiovascular death (37 events [1.8%] vs 65 events [3.1%]; HR, 0.61 [95% CI, 0.41-0.92]); and all-cause mortality (75 events [3.6%] vs 109 events [5.2%]; HR, 0.73 [95% CI, 0.54-0.98]). There was no significant effect on stroke or coronary revascularization. Adverse effects with bempedoic acid included a higher incidence of gout (2.6% vs 2.0%), cholelithiasis (2.5% vs 1.1%), and increases in serum creatinine, uric acid, and hepatic enzyme levels. In a subgroup of high-risk primary prevention patients, bempedoic acid treatment was associated with reduced major cardiovascular events. ClinicalTrials.gov Identifier: NCT02993406.

Cardiovascular events in delayed presentation of HIV: the prospective PISCIS cohort study.

People with HIV (PWH) have a higher cardiovascular risk than the general population. It remains unclear, however, whether the risk of cardiovascular disease (CVD) is higher in late HIV presenters (LP; CD4 ≤ 350 cells/μL at HIV diagnosis) compared to PWH diagnosed early. We aimed to assess the rates of incident cardiovascular events (CVEs) following ART initiation among LP compared to non-LP. From the prospective, multicentre PISCIS cohort, we included all adult people with HIV (PWH) initiating antiretroviral therapy (ART) between 2005 and 2019 without prior CVE. Additional data were extracted from public health registries. The primary outcome was the incidence of first CVE (ischemic heart disease, congestive heart failure, cerebrovascular, or peripheral vascular disease). The secondary outcome was all-cause mortality after the first CVE. We used Poisson regression. We included 3,317 PWH [26 589.1 person/years (PY)]: 1761 LP and 1556 non-LP. Overall, 163 (4.9%) experienced a CVE [IR 6.1/1000PY (95%CI: 5.3-7.1)]: 105 (6.0%) LP vs. 58 (3.7%) non-LP. No differences were observed in the multivariate analysis adjusting for age, transmission mode, comorbidities, and calendar time, regardless of CD4 at ART initiation [aIRR 0.92 (0.62-1.36) and 0.84 (0.56-1.26) in LP with CD4 count <200 and 200- ≤ 350 cells/μL, respectively, compared to non-LP]. Overall mortality was 8.5% in LP versus 2.3% in non-LP (p < 0.001). Mortality after the CVE was 31/163 (19.0%), with no differences between groups [aMRR 1.24 (0.45-3.44)]. Women vs. MSM and individuals with chronic lung and liver disease experienced particularly high mortality after the CVE [aMRR 5.89 (1.35-25.60), 5.06 (1.61-15.91), and 3.49 (1.08-11.26), respectively]. Sensitivity analyses including only PWH surviving the first 2 years yielded similar results. CVD remains a common cause of morbidity and mortality among PWH. LP without prior CVD did not exhibit an increased long-term risk of CVE compared with non-LP. Identifying traditional cardiovascular risk factors is essential for CVD risk reduction in this population.

#4271 THE GROWING BURDEN OF CHRONIC KIDNEY DISEASE IN THE UK: AN IMPACT CKD ANALYSIS

Abstract Background and Aims Chronic kidney disease (CKD) is a major source of morbidity and mortality, with an increasing incidence and prevalence worldwide. Patients with CKD experience diminished quality of life associated with increased risk of cardiovascular (CV) events, acute kidney injury (AKI), and reduced renal function. Late-stage CKD (stage 5) is also associated with significant economic burden related to renal replacement therapy (RRT). Public health and policy planning should consider the broader burden of CKD, including its societal and environmental burden, in addition to its clinical impacts and direct costs. Hence, IMPACT CKD aims to quantify the clinical, economic, humanistic, societal, and environmental burden of CKD in the United Kingdom (UK). Method A patient-level simulation model was developed to simulate the UK population using parameter data from published literature, national statistics, and health surveys. Individuals were assigned key characteristics associated with CKD, such as estimated glomerular filtration rate (eGFR), albuminuria, co-morbidities (e.g., diabetes, hypertension, heart failure), and prior CV events (e.g., myocardial infarction and stroke). Individuals were categorized as not having CKD (i.e., non-CKD) or CKD stage 1, 2, 3a, 3b, 4 or 5, based on their eGFR and albuminuria levels. Among those with CKD, patients were either classified as diagnosed or undiagnosed. Progression through the CKD stages was predicted by the simulated patient's annual eGFR rate of decline. Risk of CV and AKI events, as well as co-morbidity development were also considered in the model. Clinical progression and outcomes for the CKD population were simulated over 10 years. CKD prevalence was projected by stage and diagnosis status, as well as associated CKD and RRT costs, productivity losses from patients and caregivers, and environmental impacts as determined by CO2 emissions. Extensive validation and calibration was conducted. Results From 2022 to 2032, the prevalence of CKD is expected to increase by 4% from 8.27 million to 8.61 million people in the UK. Growth in the CKD population is driven by eGFR decline and increases in albuminuria, related to kidney function decline and AKI as the model population ages. In 2032, the prevalence of CKD by stage is projected to be 30.36%, 21.07%, 29.78%, 11.86%, 4.15%, and 2.78% in stage 1, 2, 3a, 3b, 4, and 5 patients, respectively. The diagnosed CKD population is projected to be 32.43% of the total CKD population and is primarily composed of CKD stage 3a/b, 4, and 5 patients in 2032. Patients with CKD receiving RRT are projected to increase by 44% from 73,365 in 2022 to 105,860 in 2032. The increase in late-stage CKD population is associated with an increase in RRT costs from £1.09 billion in 2022 to £1.85 billion in 2032. Over the 10-year time horizon, CKD is projected to result in 81.60 million missed workdays in diagnosed patients with CKD, and 11.89 million missed workdays by caregivers of patients with CKD. Environmental impacts equivalent to 1.35 million tonnes of CO2 emissions for patients receiving in-centre hemodialysis are predicted; however, the total environmental impact would likely be larger if the total CKD care pathway was included. Conclusion The IMPACT CKD model forecasts the prevalence and burden of CKD to remain high in the UK over the next ten years. In addition to the significant clinical burden and direct costs, CKD was also associated with extensive productivity loss and detrimental environmental impact. The model provides a validated framework for testing the sensitivity of the projections to data uncertainty, thereby identifying areas for further research.

Long-term treatment persistence and maintained reduction of LDL-cholesterol levels with evolocumab over 30 months: Results from the Spanish cohort of the European prospective HEYMANS study

AimsLimited data exist on low-density lipoprotein-cholesterol (LDL-C) level variability or long-term persistence with the monoclonal antibody evolocumab in routine clinical practice. HEYMANS (NCT02770131) is the first multi-country, multicenter, observational study of European patients initiating evolocumab as part of their routine clinical management, based on local reimbursement criteria (overall data recently published). The aim of this analysis is to describe clinical characteristics, baseline and changes in LDL-C levels, treatment patterns and persistence to evolocumab over 30 months in the Spanish cohort using data from the HEYMANS Registry. MethodsHEYMANS was a prospective study of adult patients (≥18 years) who received at least one dose of evolocumab. A total of 1951 patients were enrolled from 12 countries and were followed up for 30 months after evolocumab initiation. Data were collected for 6 months before evolocumab initiation and up to 30 months thereafter. The Spanish cohort included patients who started evolocumab in routine clinical practice from March 2016 to September 2019. Demographic and clinical characteristics, lipid-lowering therapies (LLT), and lipid levels were collected. ResultsIn total, 201 patients were included in the Spanish cohort. Median follow-up (Q1–Q3) was 30.0 (12–30) months. A total of 61.7% of patients were men and the mean (standard deviation) age was 59.5 (10.8) years. Most patients (68.7%) had experienced a prior cardiovascular event, 45.3% had coronary artery disease or stable angina, and 60.2% had a diagnosis of familial hypercholesterolemia. Overall, 57.7% of patients were receiving treatment with statins, most of them with high-intensity statins (85.3%); 45.8% of patients were intolerant to statins, and 26.4% of patients did not receive any LLT. At baseline, median (Q1–Q3) LDL-C levels were 151 (123–197) mg/dL. After 3 months of treatment, baseline LDL-C decreased by 66% to a median of 50 (30–83) mg/dL and these levels were maintained over time, with a median LDL-C of 55 (40–99) mg/dL at 30 months. At months 10–12 of treatment, LDL-C levels<55mg/dL were achieved by 56.3% of patients. LDL-C levels<70mg/dL were achieved by 70.1% of patients, and a lowering of LDL-C levels ≥50% was achieved by 76.8% of patients. The percentage of patients on evolocumab treatment was 95% at 12 months and 93% at 30 months. ConclusionsIn the Spanish cohort in routine clinical practice, evolocumab therapy provided a reduction in LDL-C levels consistent with that reported in previous clinical trials, which was sustained during 30 months of follow-up. Treatment with evolocumab was started at LDL-C levels 50% higher than those recommended by The Spanish Society of Arteriosclerosis and the Therapeutic Positioning Report. The probability of achieving the 2019 ESC/EAS LDL-C goals would improve with combination therapy and also with a lower LDL-C threshold when starting evolocumab. Persistence to evolocumab remained high during follow-up, with a very low percentage of discontinuation (5% at 12 months; 7% at 30 months).

Systolic Blood Pressure and Pulse Pressure Are Predictors of Future Cardiovascular Events in Patients with True Resistant Hypertension.

Given the increased risk of cardiovascular events associated with resistant hypertension, predictive cardiovascular prognosis is extremely important. Ambulatory blood pressure monitoring (ABPM) is mandatory for resistant hypertension diagnosis, but its use for prognosis is scarce. This observational longitudinal study included 258 patients (mean age of 60.4 ± 11.2 years; 61.2% male), who underwent 24 h ABPM in a hypertension unit from 1999 to 2019. The outcomes were global cardiovascular events (cerebrovascular, coronary, and other cardiovascular events). The mean follow-up period was 6.0 ± 5.0 years. Sixty-eight cardiovascular events (61 nonfatal) were recorded. Patients who experienced cardiovascular events were generally older, with higher rates of chronic kidney disease and prior cardiovascular events. The 24 h systolic blood pressure (hazard ratio 1.44; 95% CI 1.10-1.88), night systolic blood pressure (1.35; 95% CI 1.01-1.80), and 24 h pulse pressure (2.07; 95% CI 1.17-3.67) were independent predictors of global cardiovascular events. Multivariate Cox analysis revealed a higher risk of future cardiovascular events, particularly in patients with a 24 h daytime and nighttime pulse pressure > 60 mm Hg with respective hazard ratios of 1.95; 95% CI 1.01-3.45; 2.15; 95% CI 1.21-3.83 and 2.07; 95% CI 1.17-3.67. In conclusion, APBM is a fundamental tool not only for the diagnosis of resistant hypertension, but also for predicting future cardiovascular events.

The association of allopurinol with persistent physical disability and frailty in a large community based older cohort.

The protective effects of allopurinol on physical function in older adults are not well understood, despite its potential to improve functional gains and reduce sarcopenia. This study aims to determine the association between allopurinol, persistent physical disability, and frailty in older gout patients. This analysis used data from a randomized trial in an older cohort, ASPirin in Reducing Events in the Elderly (ASPREE). ASPREE recruited 19,114 participants aged ≥65 years without prior cardiovascular events, dementia, or independence-limiting physical disability at trial enrolment. This analysis examined the association of baseline and time-varying allopurinol use with persistent physical disability and new-onset frailty in participants with gout at baseline (self-report or use of any anti-gout medications). Frailty was measured using the Fried frailty phenotype (score ≥3/5) and a deficit accumulation frailty index (FI) (score >0.21/1.0). Multivariable Cox proportional-hazards models were used for main analyses. This analysis included 1155 gout participants, with 630 taking allopurinol at baseline and 525 not. During a median follow-up of 5.7 years, 113 new allopurinol users were identified. Compared with nonusers, baseline allopurinol use was associated with a significant risk reduction of persistent physical disability (Adjusted HR 0.46, 95% CI 0.23-0.92, p = 0.03). The strength of the association was modestly attenuated in the time-varying analysis (Adjusted HR 0.56, 0.29-1.08, p = 0.08). No significant associations with frailty measures were observed for either baseline allopurinol use (Fried frailty: Adjusted HR 0.83, 0.62-1.12; FI: Adjusted HR 0.96, 0.74-1.24) or time-varying allopurinol use (Fried frailty: Adjusted HR 0.92, 0.69-1.24; FI: Adjusted HR 1.02, 0.78-1.33). Allopurinol use in older adults with gout is associated with a reduced risk of persistent physical disability but not associated with risk of frailty.

Risk Factors for Recurrent Vitreous Hemorrhage in Type 2 Diabetes Mellitus Patients after Posterior Vitrectomy.

(Background) The aim of this study was to determine the factors related to recurrent vitreous hemorrhage (RVH) in a sample of proliferative diabetic retinopathy (PDR) patients. (Methods) This was a retrospective, review-based study. We studied 183 eyes from 121 type 2 diabetes patients with PDR. We recorded the duration of diabetes, history of hypertension, retinal photocoagulation status, posterior vitreous status, mean HbA1c and hemoglobin levels, renal function, and systemic complications associated with diabetes. We also recorded surgical variables-the presence of tractional retinal detachment, the application of segmentation and diathermy on fibrovascular proliferative tissue, and the use of silicone oil-to study which independent variables were significantly related to the presence of RVH. (Results) The duration of diabetes (p = 0.028), hemoglobin level (p = 0.02), status of the posterior vitreous (p = 0.03), retinal photocoagulation status (p = 0.002), and the presence of tractional retinal detachment (p = 0.03) were significantly associated with the presence of RVH. On the other hand, the use of diathermy was associated with fewer RVH events (p < 0.005). In addition, patients with diabetic polyneuropathy, myocardial infarction, and ischemia in the lower limbs exhibited more vitreous hemorrhage events (p < 0.001). (Conclusions) Patients with PDR and a longer diabetes duration, anemia, attached posterior vitreous, deficient retinal photocoagulation, and prior cardiovascular events were more prone to RVH.

3. Association Between Blood Pressure Variability (BPV) and Heart Failure in Elderly Hypertensive Patients: A Systematic Review

Background: Blood pressure variability (BPV) may be one of many factors that can increase the risk of cardiovascular events. However, its relationship with heart failure in elderly hypertensive patients are still less clear. Due to current situations, the implications of BPV on heart failure have been ignored, with limited application in clinical practice. Objective: To investigate the association between BPV and heart failure in elderly hypertensive patients. Method: We conducted trial and observational studies between 2018 – 2022 through PubMed and Cochrane systematically. The keywords used were “blood pressure variability”, “systolic blood pressure variability” and “heart failure”. The studies included elderly hypertensive patients (age &gt;60 years old). Primary end-point was the occurrence of heart failure. PRISMA guidelines 2020 were used for review writing. Result: Two studies with total 17.232 patients were included in this review. The subjects of these two studies were elderly hypertensive patient without any prior cardiovascular events. The characteristic of subject in these two studies were similar, with mean age of one study was and BMI while the mean age of the other one was and BMI. These all two studies showed that the high BPV increasing cardiovascular events, including hospitalization and death from heart failure. Conclusion: This review found that in elderly patients, BPV is significantly associated with the occurrence of heart failure. Therefore, these findings may have important implications for optimizing blood pressure variability monitoring and treatment strategies in those elderly hypertensive patients.

Prediabetes, diabetes and loss of disability-free survival in a community-based older cohort: a post-hoc analysis of the ASPirin in Reducing Events in the Elderly trial

Evidence for the prognostic implications of hyperglycaemia in older adults is inconsistent. To evaluate disability-free survival (DFS) in older individuals by glycaemic status. This analysis used data from a randomised trial recruiting 19,114 community-based participants aged ≥70years, who had no prior cardiovascular events, dementia and physical disability. Participants with sufficient information to ascertain their baseline diabetes status were categorised as having normoglycaemia (fasting plasma glucose [FPG] < 5.6mmol/l, 64%), prediabetes (FPG 5.6 to <7.0mmol/l, 26%) and diabetes (self-report or FPG ≥ 7.0mmol/l or use of glucose-lowering agents, 11%). The primary outcome was loss of disability-free survival (DFS), a composite of all-cause mortality, persistent physical disability or dementia. Other outcomes included the three individual components of the DFS loss, as well as cognitive impairment-no dementia (CIND), major adverse cardiovascular events (MACE) and any cardiovascular event. Cox models were used for outcome analyses, with covariate adjustment using inverse-probability weighting. We included 18,816 participants (median follow-up: 6.9 years). Compared to normoglycaemia, participants with diabetes had greater risks of DFS loss (weighted HR: 1.39, 95% CI 1.21-1.60), all-cause mortality (1.45, 1.23-1.72), persistent physical disability (1.73, 1.35-2.22), CIND (1.22, 1.08-1.38), MACE (1.30, 1.04-1.63) and cardiovascular events (1.25, 1.02-1.54) but not dementia (1.13, 0.87-1.47). The prediabetes group did not have an excess risk for DFS loss (1.02, 0.93-1.12) or other outcomes. Among older people, diabetes was associated with reduced DFS, and higher risk of CIND and cardiovascular outcomes, whereas prediabetes was not. The impact of preventing or treating diabetes in this age group deserves closer attention.