Statin Nonusers Research Articles

Plasma legumain in familial hypercholesterolemia: associations with statin use and cardiovascular risk markers

Legumain is known to be regulated in atherosclerotic disease and may have both pro- and anti-atherogenic properties. The study aimed to explore legumain in individuals with familial hypercholesterolemia (FH), a population with increased cardiovascular risk. Plasma legumain was measured in 251 subjects with mostly genetically verified FH, of which 166 were adults (≥18 years) and 85 were children and young adults (<18 years) and compared to 96 normolipidemic healthy controls. Plasma legumain was significantly increased in the total FH population compared to controls (median 4.9 versus 3.3 pg/mL, respectively, p < 0.001), whereof adult subjects with FH using statins had higher levels compared to non-statin users (5.7 versus 3.9 pg/mL, respectively, p < 0.001). Children and young adults with FH (p = 0.67) did not have plasma legumain different from controls at the same age. Further, in FH subjects, legumain showed a positive association with apoB, and markers of inflammation and platelet activation (i.e. fibrinogen, NAP2 and RANTES). In the current study, we show that legumain is increased in adult subjects with FH using statins, whereas there was no difference in legumain among children and young adults with FH compared to controls. Legumain was further associated with cardiovascular risk markers in the FH population. However the role of legumain in regulation of cardiovascular risk in these individuals is still to be determined.

Risk and effect modifiers for poor glycemic control among the chinese diabetic adults on statin therapy: the kailuan study.

Limited studies have investigated the association between statin therapy and poor glycemic control, especially in the Chinese diabetic population. Two prospective diabetes cohorts were drawn from the Kailuan Cohort. In Cohort 1, linear regression models were used to evaluate the association between statin therapy and glycated hemoglobin (HbA1c) level change. In Cohort 2, new user design and conditional logistic models were used to assess associations between statin initiation and poor glycemic control which was a composite outcome comprised of hypoglycemic agent escalation and new-onset hyperglycemia. Among 11,755 diabetic patients with medication information, 1400 statin users and 1767 statin nonusers with repeated HbA1c measurements were included in Cohort 1 (mean age: 64.6 ± 10.0years). After a median follow-up of 3.02 (1.44, 5.00) years, statin therapy was associated with higher HbA1c levels (β: 0.20%; 95%CI: 0.05% to 0.34%). In Cohort 2, 1319 pairs of matched cases/controls were included (mean age: 61.6 ± 9.75years). After a median follow-up of 4.87 (2.51, 8.42) years, poor glycemic control occurred in 43.0% of statin new users and 31.8% of statin nonusers (OR: 1.69; 95% CI: 1.32 to 2.17; P < 0.001). The statin-associated poor glycemic control risk was significantly higher among patients with lower body mass index (Pint = 0.089). Furthermore, a nonlinear association was observed between statin therapy duration and poor glycemic control (P = 0.003). Among Chinese diabetic adults, statin therapy was associated with a higher level of HbA1c, and a higher risk of hypoglycemic agent escalation and new-onset hyperglycemia, especially among those who had lower body mass index levels and longer statin therapy duration.

Association of Renal Function and Statin Therapy with Lipoprotein(a) in Patients with Type 2 Diabetes.

A high level of serum lipoprotein(a) [Lp(a)] is associated with kidney disease development in patients with type 2 diabetes (T2DM). Recent studies have suggested that statins may affect serum levels of Lp(a). However, the statin effect is not well-defined in patients with T2DM with kidney dysfunction. This retrospective study aimed to investigate the relevance of kidney dysfunction and statin therapy to Lp(a) in patients with T2DM. Japanese patients with T2DM (n=149, 96 men and 53 women) were divided into two groups: statin users (n=79) and non-statin users (n=70). Multiple logistic regression analyses were performed with Lp(a) as the objective variable and estimated glomerular filtration rate (eGFR), hemoglobin A1c, age, gender, and body mass index as the explanatory variables. Lp(a) serum levels were higher in statin users than in non-statin users (P=0.022). Multivariate regression analysis results showed an inverse correlation of eGFR to log Lp(a) in all patients (P=0.009) and in non-statin users (P=0.025), but not in statin users. In a multiple logistic regression analysis for median Lp(a), there was an inverse association between eGFR and Lp(a) level (odds ratio, 0.965; 95% confidence interval, 0.935-0.997; P=0.030) in non-statin users as well as in all participants, but not in statin users. The present study suggests that a high Lp(a) level in patients with T2DM, except in statin users, is significantly associated with decreased eGFR, indicating that the increased Lp(a) levels under statin therapy might diminish the relationship between Lp(a) and eGFR.

Statin use in resected, high-risk cutaneous melanoma: A multi-centre retrospective cohort study

BackgroundPre-clinical and clinical studies propose that statins may have chemopreventive effects against cancer, suggesting their possible roles as adjunctive therapies for melanoma. ObjectiveTo investigate the association between regular statin use and disease recurrence in patients with resected Stage I-III melanoma. MethodsWe conducted a retrospective analysis of patients enrolled in the multi-center Melanoma Research Victoria cohort with a histologically confirmed, resected American Joint Committee on Cancer Stage I-III cutaneous melanoma. Patients with uveal melanoma, melanoma of unknown primary site, or mucosal melanoma were excluded. Melanoma recurrence outcomes were compared between statin users and statin non-users, with statin use determined by linkage to the Pharmaceutical Benefits Scheme (Australia) prescription database. Results624 patients with resected Stage I-III melanoma at diagnosis were eligible for the study. 193 patients were classified as statin users and 431 patients as statin non-users. In all, 45 statin users experienced disease recurrence compared to 140 (23.3 vs 32.5%, p = 0.05) statin non-users with similar durations of follow-up (median 2.2 and 2.4 years, respectively). After adjustment, statin users had a lower risk melanoma recurrence than statin non-users (HR 0.66, 95%CI 0.44–0.99, p = 0.04). A lower risk of recurrence was also observed in subset analyzes of statin users on high-dose therapy (HR 0.50, 95%CI 0.25–0.99, p = 0.05) and patients who were adherent to statin therapy (HR 0.60, 95%CI 0.39–0.92, p = 0.02). ConclusionOur study supports the possibility that an association exists between statin use and reduced disease recurrence in resected cutaneous melanoma.

Mortality and adverse events associated with statin use in primary care patients with depression: a real-world, population-based cohort study

BackgroundNew National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially...

Association between Statin Use and Clinical Outcomes in Patients with De Novo Metastatic Prostate Cancer: A Propensity Score-weighted Analysis.

Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.

The preventative effects of statin on lung cancer development in patients with idiopathic pulmonary fibrosis using the National Health Insurance Service Database in Korea.

Little is known about the effect of statin use in lung cancer development in idiopathic pulmonary fibrosis (IPF). We analyzed the database of the National Health Insurance Service to further investigate the clinical impacts of statin on lung cancer development and overall survival (OS) in IPF patients. The analysis included 9,182 individuals diagnosed with IPF, of which 3,372 (36.7%) were statin users. Compared to statin non-users, the time from diagnosis of IPF to lung cancer development and OS were longer in statin users in IPF patients. In Cox proportional hazard regression models, higher statin compliance, statin use, and being female had an inverse association with lung cancer risk, while older age at diagnosis of IPF and smoking history were associated with higher risk of lung cancer in IPF patients. For OS, statin use, female sex, higher physical activity frequency, and diabetes were associated with longer survival. In contrast, older age at diagnosis of IPF and smoking history were associated with shorter OS in IPF patients. These data from a large population indicate that statin had an independent protective association with lung cancer development and mortality in IPF patients.

Statins and cognitive decline in patients with Alzheimer’s and mixed dementia: a longitudinal registry-based cohort study

BackgroundDisturbances in brain cholesterol homeostasis may be involved in the pathogenesis of Alzheimer’s disease (AD). Lipid-lowering medications could interfere with neurodegenerative processes in AD through cholesterol metabolism or other mechanisms.ObjectiveTo explore the association between the use of lipid-lowering medications and cognitive decline over time in a cohort of patients with AD or mixed dementia with indication for lipid-lowering treatment.MethodsA longitudinal cohort study using the Swedish Registry for Cognitive/Dementia Disorders, linked with other Swedish national registries. Cognitive trajectories evaluated with mini-mental state examination (MMSE) were compared between statin users and non-users, individual statin users, groups of statins and non-statin lipid-lowering medications using mixed-effect regression models with inverse probability of drop out weighting. A dose-response analysis included statin users compared to non-users.ResultsOur cohort consisted of 15,586 patients with mean age of 79.5 years at diagnosis and a majority of women (59.2 %). A dose-response effect was demonstrated: taking one defined daily dose of statins on average was associated with 0.63 more MMSE points after 3 years compared to no use of statins (95% CI: 0.33;0.94). Simvastatin users showed 1.01 more MMSE points (95% CI: 0.06;1.97) after 3 years compared to atorvastatin users. Younger (< 79.5 years at index date) simvastatin users had 0.80 more MMSE points compared to younger atorvastatin users (95% CI: 0.05;1.55) after 3 years. Simvastatin users had 1.03 more MMSE points (95% CI: 0.26;1.80) compared to rosuvastatin users after 3 years. No differences regarding statin lipophilicity were observed. The results of sensitivity analysis restricted to incident users were not consistent.ConclusionsSome patients with AD or mixed dementia with indication for lipid-lowering medication may benefit cognitively from statin treatment; however, further research is needed to clarify the findings of sensitivity analyses.

New statin use, mortality, and first cardiovascular events in older US Veterans by frailty status.

Statins are part of long-term medical regimens for many older adults. Whether frailty modifies the protective relationship between statins, mortality, and major adverse cardiovascular events (MACE) is unknown. This was a retrospective study of US Veterans ≥65, without CVD or prior statin use seen in 2002-2012, followed through 2017. A 31-item frailty index was used. The co-primary endpoint was all-cause mortality or MACE (MI, stroke/TIA, revascularization, or cardiovascular death). Cox proportional hazards models were developed to evaluate the association of statin use with outcomes; propensity score overlap weighting accounted for confounding by indication. We identified 710,313 Veterans (mean age (SD) 75.3(6.5), 98% male, 89% white); 86,327 (12.1%) were frail. Over mean follow-up of 8 (5) years, there were 48.6 and 72.6 deaths per 1000 person-years (PY) among non-frail statin-users vs nonusers (weighted Incidence Rate Difference (wIRD)/1000 person years (PY), -24.0[95% CI, -24.5 to -23.6]), and 90.4 and 130.4 deaths per 1000PY among frail statin-users vs nonusers (wIRD/1000PY, -40.0[95% CI, -41.8 to -38.2]). There were 51.7 and 60.8 MACE per 1000PY among non-frail statin-users vs nonusers (wIRD/1000PY, -9.1[95% CI, -9.7 to -8.5]), and 88.2 and 102.0 MACE per 1000PY among frail statin-users vs nonusers (wIRD/1000PY, -13.8[95% CI, -16.2 to -11.4]). There were no significant interactions by frailty for statin users vs non-users by either mortality or MACE outcomes, p-interaction 0.770 and 0.319, respectively. Statin use was associated with lower risk of all-cause mortality (HR, 0.61 (0.60-0.61)) and MACE (HR 0.86 (0.85-0.87)). New statin use is associated with a lower risk of mortality and MACE, independent of frailty. These findings should be confirmed in a randomized clinical trial.

The relationship between statin administration timing and survival outcomes in patients with cancer receiving immune checkpoint blockade

Objective Statins have been demonstrated to improve outcomes in patients receiving immune checkpoint blockade (ICB). This study aimed to investigate whether the timing of statin administration influences the outcomes of patients receiving ICB. Methods We conducted a retrospective cohort study utilizing electronic health records from two tertiary referral centers in Taiwan. We compared the overall survival (OS) and progression-free survival (PFS) of patients who received statins before and after ICB initiation. Results We included 734 patients who received ICB. Among them, 606 were non-statin users, 76 started statins after ICB initiation, and 52 started statins before ICB initiation. Post-ICB statin users demonstrated significantly prolonged OS (median 37.6 versus 10.3 versus 11.3 months, p = 0.009) and PFS (median 10.5 versus 6.3 versus 5.6 months, p = 0.024) compared to pre-ICB statin and non-statin users. Statin use after ICB initiation had a reduced risk of all-cause mortality (HR, 0.65 [95% CI: 0.45–0.94], p = 0.022) and progressive disease (HR, 0.71 [95% CI: 0.53–0.95], p = 0.021) by approximately 30–35%, compared to non-statin users. However, statin use prior to ICB initiation did not affect the risk of all-cause mortality or progressive disease. Similar results were observed after controlling for potential cofounders such as age, sex, cancer stage, and cancer type. Conclusions These findings suggest that initiating statin therapy after the initiation of ICB, regardless of indication, is associated with improved patient prognosis.

Statin Therapy Is Associated With a Lower Risk of Heart Failure in Patients With Atrial Fibrillation: A Population-Based Study.

Whether statin usecan reduce the risk of heart failure (HF) remains controversial. The present study evaluates the association between statin use and HF in patients with atrial fibrillation. Patients with newly diagnosed atrial fibrillation from 2010 to 2018 were included. An inverse probability of treatment weighting was used to balance baseline covariates between statin users (n=23 239) and statin nonusers (n=29 251). The primary outcome was incident HF. Cox proportional hazard models with competing risk regression were used to evaluate the risk of HF between statin users and nonusers. The median age of the cohort was 74.7 years, and 47.3% were women. Over a median follow-up of 5.1 years, incident HF occurred in 3673 (15.8%) statin users and 5595 (19.1%) statin nonusers. Statin use was associated with a 19% lower risk of HF (adjusted subdistribution hazard ratio, 0.81 [95% CI, 0.78-0.85]). Restricted to the statin users, duration of statin use was measured during follow-up; compared with short-term use (3 months to <2 years), there was a stepwise reduction in the risk of incident HF among those with 2 to <4 years of statin use (subdistribution hazard ratio, 0.86 [95% CI, 0.84-0.88]), 4 to <6 years of statin use (subdistribution hazard ratio, 0.74 [95% CI, 0.72-0.76]), and ≥6 years of statin use (subdistribution hazard ratio, 0.71 [95% CI, 0.69-0.74]). Subgroup analysis showed consistent reductions in the risk of HF with statin use. Statin use was associated with a decreased risk of incident HF in a duration-dependent manner among patients with atrial fibrillation.

Statin Use, Cholesterol Level, and Mortality Among Females With Breast Cancer

Several studies have reported an association between the use of statins and breast cancer (BC) mortality. However, most of these studies did not take into account the underlying cholesterol level. To investigate the association between serum cholesterol, statin use, and BC mortality. This cohort study included females with invasive BC that was newly diagnosed between January 1, 1995, and December 31, 2013, in Finland. The cohort had available hormone receptor data and at least 1 cholesterol measurement. All data were obtained from Finnish national registries. Statistical analyses were performed from January to May 2022. Use of statins; statin dose; and serum cholesterol, low-density lipoprotein, high-density lipoprotein, and triglyceride levels measured separately before and after BC diagnosis. Breast cancer mortality and overall mortality between date of BC diagnosis and December 31, 2015. A total of 13 378 female patients with BC (median [IQR] age, 62 [54-69] years) participated in the study. The median (IQR) follow-up was 4.5 (2.4-9.8) years after BC diagnosis, during which 16.4% of patients died and 7.0% died of BC. Prediagnostic statin use was a risk factor for BC death even after adjustment for total cholesterol level (hazard ratio [HR], 1.22; 95% CI, 1.02-1.46; P = .03). Reduced risk for BC death was seen for postdiagnostic statin use (HR, 0.85; 95% CI, 0.73-1.00; P = .05). The risk reduction was robust in participants whose cholesterol level decreased after starting statins (HR, 0.49; 95% CI, 0.32-0.75; P = .001) but was nonsignificant if cholesterol level did not subsequently decrease (HR, 0.69; 95% CI, 0.34-1.40; P = .30). Reduced BC mortality among statin users was also observed in females with estrogen receptor-positive tumors (HR, 0.82; 95% CI, 0.68-0.99; P = .03). Overall mortality was lower among statin users vs nonusers when adjusted for serum cholesterol level (HR, 0.80; 95% CI, 0.72-0.88; P < .001). Results of this cohort study showed that postdiagnostic use of statins was associated with reduced BC mortality compared with nonuse, and the risk was associated with subsequent change in serum cholesterol level. This finding suggests that cholesterol-lowering interventions with statins may be beneficial for patients with BC.

The concentration of small-diameter HDL particles (HDLp1) predicts the incidence of coronary calcium score in diabetic subjects without established cardiovascular disease

Abstract Introduction Type 2 diabetes (DM2) decisively influences the evolution of coronary atherosclerosis. However, this is a heterogeneous and poorly understood process. While in 50% of diabetics the chance of incident Coronary Calcium Score (CAC) in 5 years exceeds 40%, in 10% of diabetics the chance of incident CAC is less than 10%. To better understand the progression of coronary atherosclerosis measured by CAC in diabetics without cardiovascular disease, we studied the impact of the concentration of the small-diameter subfraction of HDL (HDLp1, 7 to 8nm). HDLp1 has been implicated as a central mediator of the anti-inflammatory effect of the HDL pool and could play a specific role in CAC incidence among diabetics. Methods From 2370 individual with two CAC evaluations and hydrogen spectroscopy/magnetic resonance (H1-NMR) plasma profile available, we found 461 diabetic individuals, non-users of statins, without previous cardiovascular disease, with CAC=0 in the first measurement and a second CAC measurement after an average period of 5 years. [HDLp1] concentration was measured by H1-NMR and divided into tertiles. The incidence of CAC was defined as an initial CAC of 0 followed by CAC&amp;gt;0 in the second measurement. Stepwise forward logistic regressions were used to identify risk factors for CAC incidence. Discrimination analysis was performed by calculating the area under the ROC curve (AUROC). Results A total of 143 (31.0%) patients had incident CAC. In stepwise logistic regression, alongside factors such as age, gender, systolic blood pressure, smoking, LDL-C, C-reactive protein and HbA1c, the 3rd tertile of [HDLp1] was associated with 55.2% (95% CI 15-110%, p =0.0039) and 140% (95% CI 32-341%, p&amp;lt;0.001) higher risk of CAC incidence compared to the 2nd tertile and 1st tertile, respectively. When compared to a model composed of 10 confounding variables (age, gender, systolic blood pressure, BMI, smoking, Lp(a), LDL-C,triglycerides, C-reactive protein and HbA1c) for predicting the incidence of CAC, the diameter of HDLp1 substantially increased the AUROC from 0.651 (95% CI 0.597-0.705) to 0.684 (95% CI 0.631–0.736), p=0.027 for the DeLong test comparing AUROCs. A restricted cubic spline demonstrated a strong association between [HDLp1] and CAC incidence. Conclusion The concentration of HDLp1 improves the predictive capacity for the incidence of CAC in diabetic individuals, non-users of statins, without cardiovascular disease.Spline HDLp1 concentration vs CAC incideROC for incident CAC

Statin use is associated with a lower risk of mortality in patients with malignant breast cancer treated with anthracyclines. A global federated health database analysis

Abstract Introduction Anthracyclines (ANT are a key component in the treatment of early breast cancer but are associated with an enhanced oxidative stress which is associated with f short- and long-term adverse events. Statins are a well-known class of lipid lowering agent with anti-inflammatory properties that could potentially counteract ANT toxicity in cancer patients. Purpose To assess the potential therapeutic benefit of statins among malignant breast cancer patients treated with ANT. Methods Retrospective study utilizing a global federated health research network (TriNetX). Patients with malignant breast cancer (ICD code C50) treated with ANT were categorized in two groups: statin users (at least 1 month before the ANT treatment); and non-statin users. The primary outcome was the 5-year risk of all-cause death. Secondary outcomes were the intra-treatment (within 6 months), post-treatment (6 months-1 year) and long-term (1 year-5 years) risk of-all cause death. A further sensitivity analysis was done to assess the risk differences between hydrophilic (rosuvastatin and pravastatin) and lipophilic (atorvastatin, simvastatin, lovastatin) statins. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Results Amongst the 36,770 patients with breast cancer identified (mean age 60±12.6 years, 98.6% female): 6,616 (17.9%) were statin users and 30,154 (81.1%) were non-statin users. Statins users were older and had more cardiovascular risk factors. After PSM, the 5-year risk of all-cause death was significantly lower in statin users (HR 0.72, 95%CI 0.63-0.83) compared to non-statins users. Analyzing the different time frames, the lowest risk of all-cause death was observed in the early period after the ATN treatment (Figure 1). The 5-year all-cause death was reduced in both the hydrophilic (HR: 0.69, 95%CI 0.58-0.83) and lipophilic statins (HR 0.72, 95%CI 0.65-0.79), when compared to non-statins users (Figure 2), with no significant differences between these two statin types (p=0.496). Conclusion Statin use was associated with a reduced risk of all-cause death in breast cancer patients treated with ATN. Further studies are needed to clarify the mechanism(s) by which statins counteract the ATN toxicity.

SLCO1B1*5 is protective against non-senile cataracts in cohort prescribed statins: analysis in a British-South Asian cohort

Abstract Background Reported association between statin use and cataract risk is controversial. The SLCO1B1 gene encodes a transport protein responsible for statin clearance. The SLCO1B1*5 reduced function variant is known to increase systemic exposure to statins. The aim of this study was to investigate a possible association between the SLCO1B1*5 reduced function variant and cataract risk in statin users of South Asian ethnicity. Methods The Genes &amp; Health cohort consists of UK participants of Bangladeshi and Pakistani ancestry. SLCO1B1*5 genotype was assessed with the Illumina GSAMD-24v3-0-EA chip. Medication data from primary care health record linkage was used to compare those who had regularly used statins compared to those who had not. Multivariable logistic regression was used to test for association between statin use and cataracts, adjusting for population characteristics and potential confounders in 36,513 participants. Multivariable logistic regression was used to test association between SLCO1B1*5 heterozygotes or homozygotes and cataracts, in subgroups having been regularly prescribed statins versus not. Results Statins were prescribed to 35% (12,704) of participants (average age 41 years old, 45% male). Non-senile cataract was diagnosed in 5% (1686) of participants. An apparent association between statins and non-senile cataract (12% in statin users and 0.8% in non-statin users) was negated by inclusion of confounders. In those prescribed a statin, presence of the SLCO1B1*5 genotype was independently associated with a decreased risk of non-senile cataract (OR 0.7 (CI 0.5-0.9, p 0.007)). Conclusions Our findings suggest that there is no independent association between statin use and non-senile cataract risk after adjusting for confounders. Among statin users, the SLCO1B1*5 genotype is associated with a 30% risk reduction of non-senile cataracts. Stratification of on-drug cohorts by validated pharmacogenomic variants is a useful tool to support or repudiate adverse drug events in observational cohorts.Study results overview

Guideline adherence to statin therapy and association with major adverse cardiac events in high-risk patients following major noncardiac surgery

Abstract Introduction Statins are widely used for the prevention of coronary artery disease (CAD) and associated secondary cardiovascular complications. Despite established evidence in acute and chronic cardiovascular disease, the optimal perioperative use of statins remains uncertain. We aimed to evaluate adherence to current guideline recommendations regarding statin therapy in high-risk patients undergoing major noncardiac surgery and its association with major adverse cardiac event (MACE). Methods Class I indications for statin therapy according to current ESC clinical practice guidelines were assessed among consecutive high-risk patients undergoing major noncardiac surgery enrolled in a prospective multicentre cohort study. The primary endpoint MACE, a composite of cardiovascular death and spontaneous acute myocardial infarction, was recorded during 120-day follow up and centrally adjudicated by cardiologists blinded to statin therapy. As a co-primary endpoint, perioperative myocardial infarction/injury (PMI) due to a type 1 MI (T1MI) or likely type 2 MI (lT2MI) within the first three postoperative days was used. After multivariable adjustment with inverse probability of treatment weighting (IPTW) to account for differences between statin and non-statin users, we performed a Cox proportional hazard model with MACE and a logistic regression model with PMI due to T1MI or lT2MI as endpoints. Results Between October 2014 and February 2018, we included 8116 high-risk patients undergoing major noncardiac surgery. 4227 of 8116 patients (52.1%) had at least one class I indication for statin therapy. The most common indication for statin use was CAD in 2235 patients (52.9%) followed by diabetes with comorbidities in 1676 patients (39.6%) and peripheral artery disease in 1514 patients (35.8%). From all patients with a class I indication for statin use, only 2440 (57.7%) were on statins preoperatively. Usage was highest in patients with prior myocardial infarction (828/1110 [74.6%]) and lowest in patients with chronic kidney disease stage 3-5 (494/996 [49.6%]). During the follow up of 120 days, 192 MACE occurred (4.6%) including 116 cardiovascular deaths. After multivariable adjustment, preoperative use of statins was associated with a reduced risk of MACE (weighted hazard ratio 0.59, 95% confidence interval [CI] 0.41-0.86; p = 0.006). PMI due to T1MI or lT2MI occurred in 508 of 4170 (12.2%) patients. After IPTW, the weighted odds ratio for PMI in patients receiving preoperative statin therapy was 1.15 (95%CI 1.01-1.31; p = 0.036). Conclusion Current adherence to guideline-recommended statin therapy in the noncardiac surgery population is suboptimal. The use of statins was associated with reduced rates of adverse cardiac events within 120 days, but not with cardiac PMI.Percentage of patients receiving statinsMACE within 120 days

Improving statins effectiveness by targeting baseline LDL cholesterol in type 2 diabetes mellitus, a systematic review and meta-analysis

Abstract Background Although the guidelines recommend statins to prevent cardiovascular events in patients with type 2 diabetes (T2D), it remains controversial whether their cardiovascular effectiveness depends on baseline LDL-Cholesterol (LDL-C) levels at the start of statin use. Purpose To determine whether the association of statin use in T2D patients with major adverse cardiovascular events (MACE) and all-cause mortality differ according to baseline LDL-C categories. Methods This study was registered in the PROSPERO database (CRD42022374004); and was performed according to the PRISMA statement. Through January 2022, Medline, Embase, and Web of science were systematically searched from inception. Observational studies in patients with T2D comparing statin users vs non-users, with reports of the baseline LDL-C levels, were included. Random-effects meta-analysis and meta-regression were performed to study if the association between statin use and the risk of all-cause mortality and MACE (a composite of myocardial infarction, hospitalization due to heart failure, stroke, and revascularization events) modified by baseline LDL-C levels. We categorized studies according to their baseline LDL-C levels into 1) &amp;lt;100 mg/dl (2.59 mmol/l), 2) 100-130 mg/dl (2.59-3.37 mmol/l) and 3) ≥130 mg/dl (3.37 mmol/l) categories. Results A total of 11 cohort studies (n= 408,937 individuals) fulfilled our criteria. The follow-up duration ranged from 1.7 to 8 years. The overall combined estimate showed that statin therapy was associated with a significantly lower risk of MACE (Hazard Ratio (HR): 0.67 [95% CI 0.57 to 0.79]) and all-cause mortality (HR: 0.60 [95% CI 0.46 to 0.79]), but varied, albeit not statistically significant, by baseline LDL-C levels. Studies with baseline LDL-C levels of 130 mg/dl or higher had the greatest reduction of MACE (HR: 0.58 [95% CI 0.37 to 0.90]) and all-cause mortality risk (HR: 0.51 [95% CI [ 0.29, 0.90]). The HRs of MACE in studies with LDL-C levels of 100-130 mg/dl and &amp;lt;100 mg/dl categories were respectively (0.66 [95% CI 0.53 to 0.82]) and (0.83 [95% CI [0.68, 1.00]); and that of all-cause mortality were respectively (0.62 [95% CI 0.38 to 1.01]) and (0.67 [95% CI [0.44, 1.02]). Statin use was associated with reductions in HRs of MACE (0.99 [95%CI, 0.98 to 1.00]; P = 0.11) and all-cause mortality (0.99 [95% CI 0.98 to 1.01]; P = 0.8) per each mg/dl increase in baseline LDL-C level in meta-regression analyses. Conclusion The results of this study suggest that the greatest cardiovascular protective effects of statin therapy in patients with T2D are attributable to patients with baseline LDL-C levels of 130 mg/dl or higher in real-life settings of observational studies.

Abstract 11710: The Integrative Experimental and Computational Approach to Assess Patient Lipid-Lowering Drug Adherence for Coronary Artery Disease Risk Diagnostics

Background: Statins, lipid-lowering drugs, are the first-line pharmaceutical therapy against Atherosclerotic Cardiovascular Disease (ASCVD). The emphasis on providing statin treatment as a preventive measure before the first cardiac event burdens low-risk individuals with adverse side effects. Furthermore, inaccurate self-reporting of statin use by patients or their poor adherence to statins complicates the monitoring of long-term benefits and side effects of statins and ASCVD risk assessment. New sensitive, multiplexed and high throughput methods to confirm actual statin use by patients are urgently needed. Methods: We used 690 plasma samples from individuals with known number of diseased vessels, established lipid profiles, and medication records of statin use. The samples were obtained from the CATHeterization GENetics (CATHGEN) sample archive. The levels of 7 statins (atorvastatin, simvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and fluvastatin) in the plasma samples were determined by a 4-minute-long Liquid Chromatography-Mass Spectrometry Method (LC-MS/MS). Nominal logistic regression algorithms were employed to model coronary artery disease (CAD) outcomes with the incorporation of statin use, phenotypic, and lipid profile characteristics. Results: Our LC-MS/MS analysis has revealed discrepancies between the reported statin medication use and the detected statin levels in plasma. The reported statin use history was confirmed for 212 out of 261 patients. Among 429 specimens without a recorded history of statin use, statin was detected in 198 specimens. Comparison of logistic regression models built with statin use data as a covariate and with stratification by statin users and non-users revealed significant differences in covariate corrected mean lipid profile measures and their association with predicted atherosclerosis outcomes. Conclusion: In summary, high-throughput multiplexed LC-MS/MS analysis is highly applicable to uncover discrepancies between the self-reported and actual use of statins. By combining LC-MS/MS with statistical modeling, we showed that these discrepancies may significantly affect the modeled association between lipid profile measures and ASCVD outcome.

Abstract 15447: The Association of Maternal Statin Use During Pregnancy to Perinatal Outcomes

Introduction: Statins are used to treat those with hyperlipidemia and at high risk for a cardiovascular event, including women of childbearing potential. Traditionally, statins have been contraindicated during pregnancy because of a theoretical risk of teratogenicity. The FDA removed the black box warning for usage during pregnancy in 2021and recent observational studies have reported a relatively safe profile of statin use during pregnancy. However, ongoing evidence is needed because of the small samples and limited data available. Therefore, the objective of this study is to report perinatal outcomes of statin use during pregnancy. Methods: Patients taking a statin while pregnant were matched 1:10 to non-statin pregnant patients by age (±1 years), date of delivery (±2 years), hypertension, diabetes, and smoking history. All patients were &gt; 18 years of age and received prenatal and delivery care between 1997 and 2021 at Intermountain Health, a system of 24 hospitals and 215 clinics in Utah, Idaho, and Nevada. Data for this study utilized electronic health records stored in Intermountain’s data warehouse. Results: A total of 57 statin-user pregnancies were well-matched to 570 non-statin user pregnancies (Table 1). No significant differences were found between the groups for miscarriage, pre-term delivery, preclampsia/eclampsia, and congenital anomalies (Table 2). Mean length of statin use prior to pregnancy was 1.3±2.5 years. Among those without miscarriages, 59.6% discontinued statin use, with a mean length of use while pregnant before discontinuation being 5 months. Conclusions: This study suggests that statin use while pregnant may be safe with no congenital anomalies being found. However, ongoing surveillance is needed because of the small sample size of statin users that can make it difficult to detect associations.

Association between lipid levels and the risk of Parkinson's disease in individuals with diabetes mellitus: A nationwide population-based cohort study

IntroductionMany studies have examined the positive association between diabetes mellitus (DM) and the risk of Parkinson's disease (PD). Dyslipidemia has been reported to be prevalent in patients with diabetes; thus, lipid levels and the drugs for dyslipidemia could influence the development of PD in patients with DM. This study aimed to examine the association between lipid levels and the risk of PD in individuals with DM and evaluate whether the association changes with the use of statins. MethodsThis nationwide population-based retrospective cohort study included individuals with DM according to the International Classification of Diseases between 2009 and 2012. Among the 2,361,633 patients with DM followed up for up to 9 years, 17,046 were newly diagnosed with PD. Patients with DM were categorized into quartile groups of total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels. ResultsThere was an inverse association between lipid levels and PD development in the unadjusted model; however, this relationship became less significant after adjusting the use of statins in triglyceride and total cholesterol. In the analysis stratified by statin use, total cholesterol level was associated with decreased PD risk in non-statin users with DM; however, there was no significant association between total cholesterol level and PD risk in statin users. ConclusionWe found an inverse relationship between lipid levels and PD risk in patients with DM, which was influenced by statin use. Future studies about optimal target lipid levels relevant to PD risk considering statin dose in DM patients are needed.