Composite Cardiovascular Disease Endpoint Research Articles

Awareness of Being Prescribed Antihypertensive Medications and Cardiovascular Outcomes.

Hypertension is a major cause of cardiovascular disease (CVD). In patients with hypertension, unawareness of the disease often results in poor blood pressure control and increases the risk of CVD. However, data in nationwide surveys regarding the proportion of unaware individuals and the implications of such on their clinical outcomes are lacking. We aimed to clarify the association between unawareness of being prescribed antihypertensive medications among individuals taking antihypertensive medications and the subsequent risk of developing CVD. This retrospective cohort study analyzed data from the JMDC Claims Database, including 313,715 individuals with hypertension treated with antihypertensive medications (median age 56 years). The primary endpoint was a composite of myocardial infarction, angina pectoris, stroke, heart failure, and atrial fibrillation. Overall, 19,607 (6.2%) individuals were unaware of being prescribed antihypertensive medications. During the follow-up period, 33,976 composite CVD endpoints were documented. Despite their youth, minimal comorbidities, and the achievement of better BP control with a reduced number of antihypertensive prescriptions, unawareness of being prescribed antihypertensive medications was associated with a greater risk of developing composite CVD. Hazard ratios of unawareness of being prescribed antihypertensive medications were 1.16 for myocardial infarction, 1.25 for angina pectoris, 1.15 for stroke, 1.36 for heart failure, and 1.28 for atrial fibrillation. The results were similar in several sensitivity analyses, including the analysis after excluding individuals with dementia. Among individuals taking antihypertensive medications, assessing the awareness of being prescribed antihypertensive medications may help identify those at high risk for CVD-related events.

Cardiovascular disease and stroke following cancer and cancer treatment in older adults

AbstractBackgroundCancer survivors can be at risk of cardiovascular disease (CVD) because of either their malignancy or its treatment. Although studies linking cancer and CVD exist, few examine risk in older adults, the impact of cancer treatment, or the effect of aspirin on reducing risk in this cohort.MethodsThe authors conducted a secondary analysis of the Aspirin in Reducing Events in the Elderly (ASPREE) trial to investigate the impact of cancer and cancer treatment on a composite CVD end point comprising hospitalization for heart failure (HHF), myocardial infarction (MI), and stroke.ResultsOf 15,454 Australian and US ASPREE participants, 1392 had an incident cancer diagnosis. Rates of CVD were greater in the cancer risk‐set compared to the cancer‐free risk‐set (20.8 vs. 10.3 events per 1000 person‐years; incidence rate ratio, 2.03; 95% confidence interval, 1.51–2.66), with increased incidence seen across MI, HHF, overall stroke, and ischemic stroke. Increased incidence remained after adjustment for clinically significant risk factors for CVD. Incidence was greatest in metastatic, hematological, and lung cancer. Chemotherapy was associated with increased risk of CVD. Similar rates of CVD were seen across aspirin and placebo groups.ConclusionsIncidence of CVD, including MI, HHF, and ischemic stroke, was increased in older adults with cancer. Aspirin did not impact CVD incidence. Risk may be higher in those with metastatic, hematological, and lung cancer, and following chemotherapy.

Chronic Obstructive Pulmonary Disease Exacerbations Increase the Risk of Subsequent Cardiovascular Events: A Longitudinal Analysis of the COPDGene Study.

Cardiovascular disease (CVD) is the most important comorbidity in patients with chronic obstructive pulmonary disease (COPD). COPD exacerbations not only contribute to COPD progression but may also elevate the risk of CVD. This study aimed to determine whether COPD exacerbations increase the risk of subsequent CVD events using up to 15 years of prospective longitudinal follow-up data from the COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease) study. The COPDGene study is a large, multicenter, longitudinal investigation of COPD, including subjects at enrollment aged 45 to 80 years with a minimum of 10 pack-years of smoking history. Cox proportional hazards models and Kaplan-Meier survival curves were used to assess the risk of a composite end point of CVD based on the COPD exacerbation rate. Frequent exacerbators exhibited a higher cumulative incidence of composite CVD end points than infrequent exacerbators, irrespective of the presence of CVD at baseline. After adjusting for covariates, frequent exacerbators still maintained higher hazard ratios (HRs) than the infrequent exacerbator group (without CVD: HR, 1.81 [95% CI, 1.47-2.22]; with CVD: HR, 1.92 [95% CI, 1.51-2.44]). This observation remained consistently significant in moderate to severe COPD subjects and the preserved ratio impaired spirometry population. In the mild COPD population, frequent exacerbators showed a trend toward more CVD events. COPD exacerbations are associated with an increased risk of subsequent cardiovascular events in subjects with and without preexisting CVD. Patients with COPD experiencing frequent exacerbations may necessitate careful monitoring and additional management for subsequent potential CVD. URL: https://www.clinicaltrials.gov; Unique identifier: NCT00608764.

Unawareness of being prescribed medications for diabetes and incident cardiovascular disease

BackgroundSome patients with diabetes are unaware that they are prescribed medications for diabetes. The purpose of this study is to determine, using a Japanese nationwide epidemiologic database, the association between unawareness of being prescribed medication for diabetes and the risk of developing cardiovascular disease (CVD) in patients with diabetes. MethodsThis observational cohort study analyzed data from the JMDC Claims Database between 2005 and 2022, including 94,048 patients with diabetes treated with medications. The primary endpoint was a composite endpoint including myocardial infarction (MI), stroke, heart failure (HF), and atrial fibrillation (AF). ResultsWe identified 7561 composite CVD endpoints during a mean follow-up of 1199 ± 902 days. Overall, 7779 (8.3 %) patients were unaware of being prescribed medications for diabetes. Those who did not know they were prescribed drugs were younger and had better glycemic control, but these individuals were at higher risk of developing combined CVD [hazard ratio (HR) 1.13, 95 % confidence interval (95 % CI) 1.04–1.22]. HRs of unawareness of being prescribed medications for diabetes were 1.33 (95 % CI 1.06–1.68) for MI, 1.13 (95 % CI 0.97–1.31) for stroke, 1.10 (95 % CI 1.00–1.21) for HF, and 1.19 (95 % CI 0.97–1.47) for AF, respectively. ConclusionsIn patients with diabetes taking medications for diabetes, even if they are young and have good glycemic control, unawareness of being prescribed medications for diabetes was associated with a greater risk of developing CVD. It is important that they receive adequate education from their healthcare providers to accurately identify their treatment status.

Hypertensive retinopathy and cardiovascular disease risk: 6 population-based cohorts meta-analysis

BackgroundThe cardiovascular risk associated with different levels of hypertensive retinopathy, including mild, remains unclear. We performed an individual participant meta-analysis from 6 population-based cohort studies to determine the relationship of hypertensive retinopathy with incident cardiovascular outcomes. MethodsWe identified cohort studies that objectively assessed hypertensive retinopathy from photographs, documented incident cardiovascular outcomes, and were population-based. Six studies contributed data from 11,013 individuals at baseline with 5–13 years follow-up. Participants were recruited if they had hypertension and did not have confounding conditions such as diabetic retinopathy. Main outcome measures were incident coronary heart disease (CHD), stroke and a composite endpoint of cardiovascular disease (CHD or stroke). Pooled estimates of incident risk ratios (IRR) were obtained after adjusting for age, gender, systolic blood pressure, serum total cholesterol, high density lipoprotein and smoking. ResultsAmong eligible participants with hypertension and without diabetes, there were 1018/9662 (10.5%) incident CHD events, 708/11,013 (6.4%) incident stroke events and 1317/9378 (14.0%) incident CVD events. Mild hypertensive retinopathy was associated with increased risk of CVD (IRR 1.13, 95% CI 1.00 to 1.27) and CHD (IRR 1.17, 95% CI 1.02 to 1.34) but not stroke; moderate hypertensive retinopathy was associated with increased risk of CVD (IRR 1.25 95% CI 1.02 to 1.53) but not stroke or CHD individually. ConclusionsIn persons with hypertension, both mild and moderate hypertensive retinopathy were associated with higher CVD risk.

VEGF Inhibition in Retinal Vein Occlusion Does Not Associate with Cardiovascular Morbidity or Mortality

Intravitreal treatment with VEGF inhibitors has proven safe in clinical trials, but often on selected patient groups and without statistical power to investigate rare safety events. Data on anti-VEGF treatment in patients with retinal vein occlusion (RVO) are sparsely represented, and studies providing population-based, long-term follow-up are needed to assess the risks in routine clinical practice. We aimed to evaluate the association between treatment with anti-VEGF and the risk of incident cardiovascular disease (CVD) and all-cause mortality in patients with RVO, and whether this association was affected by selected risk factors. A cohort study from January 2012 to December 2018 using Danish nationwide registries linked on an individual level. Patients with RVO (n= 7235), exposed (n= 3508), and unexposed (n= 3727) to anti-VEGF, aged ≥ 40 years, alive, and living in Denmark. Cox proportional hazards analysis evaluating the effect of intravitreal VEGF inhibitory treatment on incident CVD and all-cause mortality. A predefined analysis plan specified primary outcomes as hazard ratios (HRs) of a composite CVD endpoint and all-cause mortality in patients treated with anti-VEGF compared with untreated. Secondary outcomes included cumulative dose analysis, HRs on subgroups of CVD, and stratified analyses evaluating the effect of sex, age, diabetes, intensive treatment, and preexisting CVD on the HRs. We found no increased risk of composite CVD (HR, 1.07; 95% confidence interval [CI], 0.89-1.29) or all-cause mortality (HR, 0.88; 95% CI, 0.77-1.00) in patients with RVO treated with anti-VEGF. In the secondary analyses, we found no dose-response relationship. We found an increased risk of intracranial hemorrhage (HR, 1.66; 95% CI, 1.02-2.71), but no increased risks in remaining subgroups of CVD. We found no increased risk associated with selected predisposing risk factors, and no increased risk in patients with preexisting CVD. Treatment with anti-VEGF in patients with RVO is safe, when evaluated in a nationwide, population-based setting. An increased risk of intracranial hemorrhage might be present, but cannot be reliably quantified and should be further elucidated by larger population-based studies including all indications for anti-VEGF treatment. Proprietary or commercial disclosure may be found after the references.

The association of BP with cardiovascular outcomes in patients with dipstick proteinuria and preserved kidney function.

Little is known about the relationship between blood pressure (BP) and incident cardiovascular disease (CVD) in people with proteinuria and a preserved estimated glomerular filtration rate (eGFR). This study sought to investigate the association of BP with CVD risk in adults with proteinuria and preserved eGFR. We studied 188,837 individuals with proteinuria and preserved eGFR ≥60 mL/min/1.73 m2. We categorized individuals who were not taking BP-lowering medications into four groups based on the 2017 American College of Cardiology/American Heart Association BP guideline and categorized those who were taking BP-lowering medications using the same BP ranges. The primary outcome was a composite CVD endpoint that included myocardial infarction, angina pectoris, stroke, and heart failure. Over a mean follow-up of 1,050 days, 7,039 CVD events were identified. Compared with normal BP, stage 1 hypertension (hazard ratio [HR]: 1.30, 95% confidence interval [95% CI]: 1.21-1.40) and stage 2 hypertension (HR: 2.17, 95% CI: 2.01-2.34) were associated with an increased risk for CVD events among medication-naïve individuals. Only stage 2 hypertension range (HR: 1.19, 95% CI: 1.02-1.38) was associated with an increased CVD event risk among people taking BP-lowering medications. Restricted cubic spline analysis showed that the risk of CVD events increased monotonically with BP at an SBP/DBP > 120/80 mmHg among medication-naïve individuals, but risk increased only at an SBP/DBP > 140/90 mmHg among individuals taking BP-lowering medications. In conclusion, among people with proteinuria and preserved eGFR, stage 1 and stage 2 hypertension were associated with a greater risk of CVD among medication-naïve individuals, whereas only stage 2 hypertension was associated with an increased CVD risk among those taking BP-lowering medications.

Reduction in blood pressure for people with isolated diastolic hypertension and cardiovascular outcomes.

Isolated diastolic hypertension (IDH) is a largely underrated risk factor for cardiovascular disease (CVD). It is currently unclear whether a reduction in blood pressure (BP) is associated with CVD events among adults with IDH. We aimed to elucidate the relationship between BP reduction and incident CVD in individuals with IDH. We retrospectively analysed the data of 71 297 individuals with IDH. Isolated diastolic hypertension was defined as systolic BP of < 140 mmHg and diastolic BP (DBP) of ≥90 mmHg (median age, 48 years; 83.1% men; median DBP, 92 mmHg). None of the participants took BP-lowering medications or had a history of CVD at baseline. Blood pressure was measured at baseline and 1-year follow-up, and participants were categorized into two groups based on DBP at 1 year (≥90 or < 90 mmHg). The primary outcome was a composite endpoint that included myocardial infarction, stroke, and all-cause death. Over a mean follow-up period of 1100 ± 859 days, 1317 composite CVD endpoints were recorded. Participants with DBP of < 90 mmHg at 1 year were at a lower risk of composite CVD events [hazard ratio (HR): 0.75, 95% confidence interval (CI): 0.67-0.83] than those with DBP of ≥90 mmHg at 1 year. A reduction in DBP per 5 mmHg during the 1-year follow-up was associated with a lower composite CVD event risk (HR: 0.92, 95% CI: 0.89-0.95). The results remained consistent across a multitude of sensitivity analyses. Our analysis of a large-scale epidemiological dataset demonstrated a relationship of reduction in DBP with a reduced risk for CVD events in individuals with IDH.

MO468: Moving More Associates With Reduced Risk of Cardiovascular Disease and Death Across All Stages of Chronic Kidney Disease: A UK Biobank Study

Abstract BACKGROUND AND AIMS Physical activity (PA) is widely recommended for the prevention of chronic conditions including cardiovascular (CV) disease. In chronic kidney disease (CKD), it is unclear whether PA confers a similar benefit. We examined whether the duration and intensity of PA are associated with the risk of CV disease and mortality and whether the relationship differs in CKD. METHOD Participants were from UK Biobank: a prospective cohort study with over 500 000 participants. The estimated glomerular filtration rate was calculated using cystatin C (eGFRcys). CKD was defined according to the KDIGO guidelines and participants were categorized as no CKD (eGFRcys &amp;gt; 90mL/min/1.73m2), CKD G1-2 (eGFRcys 60–89mL/min/1.73m2) or CKD G3-5 (eGFRcys &amp;lt; 60mL/min/1.73m2). Exercise duration and intensity were self-reported using the international physical activity questionnaire (IPAQ) and participants were categorized into four groups: inactive (reference), low, moderate and vigorous PA, according to World Health Organisation (WHO) weekly PA recommendations. Cox proportional hazards models tested associations between PA category and a composite endpoint of CV disease (myocardial infarction or stroke) or all-cause mortality across CKD categories. Models were adjusted for other known risk factors for CV disease and death including age, smoking status, blood pressure, eGFRcys and albuminuria. RESULTS Of 502 460 participants in UK Biobank, 123 167 were excluded because of missing biochemistry or IPAQ data and a further 21 084 were excluded because of pre-existing CV disease: 358 209 participants were included in the analyses. Of these 182 457 (51.0%) were classed as no CKD, 162 621 (45.4%) as CKD G1-2 and 13 131 (3.7%) as CKD G3-5. A total of 48 369 (13.5%) of participants were classed as inactive and 211 591 (16.5%) as undertaking vigorous PA. In participants without CKD, any PA above inactivity was associated with a reduced risk of reaching the combined endpoint by approximately 20% (low: hazard ratio, HR 0.77, 95% confidence interval, CI 0.67–0.89; moderate: HR 0.80, 95%CI 0.70–0.91; vigorous: HR 0.81, 95%CI 0.73–0.90, P &amp;lt; 0.001). This relationship is maintained in CKD G1-2, but in CKD G3-5, moderate (HR 0.75, 95%CI 0.61–0.93) and vigorous (HR 0.77, CI 0.66–0.89, P &amp;lt; 0.001) activity are associated with reduced risk of the combined endpoint (Table 1). Interestingly across all categories of CKD, the majority of participants considered that they undertook more than the WHO minimum recommended PA per week. CONCLUSION Achieving the minimum weekly targets for PA set by WHO is associated with a significantly reduced risk of a combined endpoint of CV disease and death. This relationship is preserved in those with CKD G1-2, even when adjusted for other recognized risk factors. The benefit is seen in CKD G3-5 with increased intensity of PA, above the WHO minimum. PA data is self-reported which limits the accuracy and association does not prove causality. However, patients with CKD have a much higher risk of CVD and death and PA is a simple, low-cost intervention that warrants further study to improve CV morbidity and all-cause mortality amongst people with CKD.

IDF21-0485 Hyperglycaemia in pregnancy is associated with cardiovascular and renal risk among Aboriginal women in Australia

Background: Around the world, First Nations peoples in countries with similar histories of colonisation experience substantial health and socioeconomic disparities. Aboriginal people in the Northern Territory (NT) of Australia have a high burden of type 2 diabetes, cardiovascular disease (CVD) and chronic kidney disease (CKD). Rates of hyperglycaemia in pregnancy, including both gestational diabetes (GDM) and pre-existing diabetes, are increasing. Internationally, GDM has been associated with future CVD, but the relationship with CKD is less clear. Pregnancy may be a valuable opportunity to evaluate and manage future cardiometabolic risk given routine diabetes screening and near universal healthcare engagement. Aim: To investigate CVD and CKD risk among Aboriginal women with GDM and pre-existing diabetes compared to those without known diabetes during pregnancy. Method: A retrospective, longitudinal cohort study was performed among Aboriginal women who gave birth from 2000 to 2016, using linked data from the NT Perinatal Data Collection and NT Hospital Inpatient Activity dataset (2000–2018). Pre-specified outcomes included hospital admissions for a composite CVD endpoint (ischaemic heart disease, stroke or peripheral vascular disease), heart failure, CKD (any stage) and end stage kidney disease (ESKD). Time-to-event analyses were undertaken using Cox proportional hazards regression (Table). Results: The cohort included 10,931 Aboriginal women. At the index pregnancy, mean age was 23.1 (SD 6.2) years, 755 (6.9%) had GDM and 241 (2.2%) had pre-existing diabetes. Median follow-up was 12.1 (IQR 7.2–15.8) years. Compared to those without diabetes, women with GDM or pre-existing diabetes had increased risk for CVD, heart failure, CKD and ESKD.Tabled 1OutcomeEvent rates, n(%)HR (95% CI)* vs. no known diabetes during pregnancyNo known diabetesGDMPre-existing diabetesGDMPre-existing diabetesCVD242 (2.4)49 (6.5)34 (14)2.7 (1.9-3.8)3.4 (2.1-5.3)Heart failure174 (1.8)25 (3.3)19 (7.9)2.7 (1.6-4.4)5.3 (2.9-9.6)CKD250 (2.5)74 (9.8)89 (37)5.1 (3.8-6.8)14 (9.6-19)ESKD50 (0.5)21 (2.8)29 (12)10 (5.5-20)34 (17-68) Open table in a new tab *Adjusted for age, hypertensive disorder, parity, remoteness and smoking during index pregnancy. Discussion: In this relatively young cohort of Aboriginal women in Australia, GDM and pre-existing diabetes in pregnancy were strongly associated with development of cardiovascular and kidney disease. Culturally appropriate post-partum strategies to reduce cardiometabolic risk should be investigated along with public health strategies that address the social determinants of health.

Impaired fasting glucose, type 2 diabetes mellitus, and lifetime risk of cardiovascular disease among women and men: the Rotterdam Study

IntroductionData on sex-specific lifetime risk of cardiovascular disease (CVD) across the glycemic spectrum, in particular in impaired fasting glucose (IFG) state, are scarce. Whether overweight/obesity modifies the CVD burden also...

Visit-to-visit office blood pressure variability revisited in SPRINT.

Visit-to-visit office blood pressure variability revisited in SPRINT.

Aortic Stiffness, Inflammation, and Incidence of Cardiovascular Events in Elderly Participants From the General Population.

Low-grade inflammation and arterial stiffness are key factors in the development of vascular aging. However, the interplay between arterial stiffness and inflammation for cardiovascular (CV) disease is unclear. Aortic pulse wave velocity (aPWV) and the inflammatory markers, high-sensitivity C-reactive protein (CRP) and orosomucoid, were measured in 2710 participants (median age: 72 years). These participants were followed up for a mean of 7.6 years for a composite CV disease end point. Per 1 interquartile range increment of CRP and orosomucoid, respectively, aPWV increased by 0.19 m/s (95% CI: 0.07-0.32) and 0.19 m/s (0.11-0.27), after multifactorial adjustment. Mediation analysis showed that aPWV, after multifactorial adjustment, mediated 8% (-4, 20) of the CV disease risk associated with CRP and 8% (-4, 18) of orosomucoid risk. The associated risk increased with combinations of high aPWV and high CRP or orosomucoid. We found no evidence that arterial PWV acted as an important mediator of the relationship between systemic inflammation and CV disease risk in this elderly population. The results instead indicate an additive effect. Our study supports the view that arterial stiffness and chronic inflammation affects CV risk mainly through separate causal pathways.

Medications for gout and its comorbidities: mutual benefits?

To review recent literature with relevance to the management of multimorbid patients with gout, i.e., gout medication repurposed for comorbidities and vice versa. Adding to the previous success of interleukin-1 inhibition, two trials on low-dose colchicine's role in cardiovascular disease (CVD) demonstrated potential benefits in patients with or without gout. In Colchicine Cardiovascular Outcomes Trial, a composite CVD endpoint was reduced by 23% among patients who had experienced a recent myocardial infarction. In Low-Dose Colchicine 2, the composite CVD endpoint was reduced 31% among those with stable coronary artery disease. Use of urate-lowering therapy (ULT) for renal protection in patients without gout produced null results. Allopurinol did not benefit the glomerular filtration rate in two trials (Controlled trial of slowing of Kidney Disease progression From the Inhibition of Xanthine oxidase and Preventing Early Renal Function Loss) among patients with chronic kidney disease (with or without hyperuricemia, but not gout). SGLT-2 inhibitors, a medication recommended for patients with diabetes and CVD, diabetic kidney disease, or heart failure, demonstrated a protective effect against gout flares in a secondary trial analysis and a large observational study. The role of colchicine may expand beyond gout flare prevention to patients with existing CVD. The renal benefit of ULT among patients with gout remains unclear. SGLT-2 inhibitors may benefit diabetic patients who have gout as a comorbidity.

LEADER Trial Eligibility and Preventable Cardiovascular Events in US Adults with Diabetes: the National Health and Nutrition Examination Surveys 2007-2016.

The Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial showed the cardiovascular disease (CVD) benefits of liraglutide therapy among patients with type 2 diabetes mellitus (T2DM). We applied this trial to US adults with T2DM in terms of eligibility and preventable CVD events. We included US adults with T2DM from the National Health and Nutrition Examination Survey (NHANES) 2007-2016. Eligibility criteria from LEADER primary and secondary prevention cohorts were applied to determine potentially eligible US adults. We estimated the number of primary composite and secondary CVD endpoints that would occur based on LEADER treated and placebo published event rates, with the difference indicating the number of preventable events. Among 4672 (projected to 27.3 million [M]) adults we identified with T2DM, we estimated 800 (4.2 million) (15.4%) to fit LEADER eligibility criteria, including 205 (0.9 M) primary prevention 595 (3.3 M) secondary prevention subjects. Compared to LEADER trial participants, our sample had higher proportions of women and minorities, prior angina, chronic kidney disease, and lipid-lowering medication use. We estimated 21,209 primary composite CVD events, 29,691 extended CVD composite outcomes, 16,967 all-cause deaths, 16,967 cardiovascular deaths, 12,725 myocardial infarctions, and 12,725 microvascular events would be prevented annually if our eligible T2DM subjects were on liraglutide. Liraglutide may prevent many fatal and non-fatal CVD events if provided to US adults meeting LEADER eligibility criteria. More efforts are needed to educate the healthcare providers on the CVD benefits from newer diabetes therapies, including liraglutide.

Greater variability in lipid measurements associated with cardiovascular disease and mortality: A 10‐year diabetes cohort study

AimTo examine the associations between variability in lipids and the risk of cardiovascular disease (CVD) and mortality in patients with type 2 diabetes based on low‐density lipoprotein‐cholesterol (LDL‐C), the total cholesterol (TC) to high‐density lipoprotein‐cholesterol (HDL‐C) ratio and triglycerides (TG).Materials and methodsA retrospective cohort study included 125 047 primary care patients with type 2 diabetes aged 45‐84 years without CVD during 2008‐2012. The variability of LDL‐C, TC to HDL‐C and TG was determined using the standard deviation of variables in a mixed effects model to minimize regression dilution bias. The associations between variability in lipids and CVD and mortality risk were assessed by Cox regression. Subgroup analyses based on patients’ baseline characteristics were also conducted.ResultsA total of 19 913 CVD events and 15 329 mortalities were recorded after a median follow‐up period of 77.5 months (0.8 million person‐years), suggesting a positive linear relationship between variability in lipids and the risk of CVD and mortality. Each unit increase in the variability of LDL‐C (mmol/L), the TC to HDL‐C ratio and TG (mmol/L) was associated with a 27% (HR: 1.27 [95% CI: 1.20‐1.34]), 31% (HR:1.31 [95% CI: 1.25‐1.38]) and 9% (HR: 1.09 [95% CI: 1.04‐1.15]) increase in the risk of composite endpoint of CVD and mortality, respectively. Age‐specific effects were also found when comparing LDL‐C variability, with patients aged 45‐54 years (HR: 1.70 [95% CI: 1.42‐2.02]) exhibiting a 53% increased risk for the composite endpoints than those aged 75‐84 years (HR: 1.11 [95% CI: 1.01‐1.23]). Similar age effects were observed for both the TC to HDL‐C ratio and TG variability. Significant associations remained consistent among most of the subgroups.ConclusionsVariability in respective lipids are significant factors in predicting CVD and mortality in primary care patients with type 2 diabetes, with the strongest effects related to LDL‐C and the TC to HDL‐C ratio and most significant in the younger age group of patients aged 45‐54 years. Further study is warranted to confirm these findings.

1422-P: Different Diagnostic Criteria for Diabetes and Risk of Cardiovascular Disease in the Greenland Inuit

Introduction: Diabetes prevalence in Greenland is high and increasing. Diabetes can be diagnosed by different criteria; currently HbA1c levels ≥ 48 mmol/mol, fasting plasma glucose (FPG) ≥ 7.0 mmol/l and/or two-hour plasma glucose (2hPG) ≥ 11.1 mmol/l after an oral glucose tolerance test (OGTT). We compared the risk of cardiovascular disease (CVD) by different diagnostic criteria, in the Greenland Inuit. Methods: Participants included in the population-based Inuit Health in Transition (IHIT) study in Greenland (2005-2010), had HbA1c, FPG and 2hPG levels measured at entry. We followed participants in the Danish and Greenlandic health registers for a composite endpoint of non-fatal and fatal CVD until 31/12-2017. Participants with known diabetes (n=77) and previous CVD (n=140), were excluded. We compared incidence rates for different diagnostic criteria, adjusted for various clinical and sociodemographic confounders in separate Poisson regressions, using multiple imputations for missing data and split follow-up into 1-year age-bands to account for a non-constant effect of age. Results: We included 2,898 adult participants, with 246 CVD events and 366 deaths during follow-up. In the crude analyses, incidence rate ratios (IRR) of CVD were highest among participants diagnosed by HbA1c (IRR:2.69; 95%CI (1.66-4.34)), followed by participants diagnosed by FPG (2.04 (1.27-3.27)), and both FPG and 2hPG (1.96 (1.31-2.94)), compared with normoglycemia. The IRR for all three diagnostic criteria were attenuated after confounder adjustment (HbA1c 1.14 (0.70-1.88); FPG: 0.81 (0.50-1.30); FPG and 2hPG: 0.78 (0.51-1.18)). Conclusions: IRR of CVD were highest among participants diagnosed by HbA1c in the crude analyses. None of the diagnostic criteria were associated with CVD after adjustment, especially for age. Future studies will investigate other diabetes related complications, competing risks from death, and interactions with genetic variants in the Greenland population. Disclosure S. Byberg: None. M. Tvermosegaard: None. L. Díaz: None. N.K. Senftleber: None. C.V.L. Larsen: None. P.F. Rønn: Research Support; Self; Amgen, Danish Diabetes Academy. Stock/Shareholder; Spouse/Partner; Novo Nordisk A/S. P. Bjerregaard: None. M.L. Pedersen: None. M.E. Jørgensen: Research Support; Self; Amgen, AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi-Aventis. Stock/Shareholder; Self; Novo Nordisk A/S.

Impact of LR11 as Residual Risk on Long-Term Clinical Outcomes in Patients with Coronary Artery Disease Treated with Statins after First Percutaneous Coronary Intervention.

Cardiovascular events still occur despite statin-based lipid-lowering therapy in patients with coronary artery disease (CAD). LR11, a member of the low-density lipoprotein receptor family, is a novel marker for the proliferation of intimal smooth muscle cells, which are critical to atherosclerotic plaque formation. We evaluated the impact of LR11 on long-term clinical outcomes in CAD patients treated with statins after percutaneous coronary intervention (PCI).This study included 223 consecutive CAD patients (age, 64.5 ± 9.6 years; male, 81.2%) treated with statin after first PCI between March 2003 and December 2004 at our institution. Patients were stratified to two groups according to LR11 levels (median). Composite cardiovascular disease (CVD) endpoints that included cardiovascular death, non-fatal acute coronary syndrome and non-fatal stroke were compared between groups.The rate of CVD endpoints was significantly higher in the high LR11 group (log-rank, P = 0.0029) during the median follow-up period of 2844 days. Multivariate Cox regression analysis showed that a higher LR11 level was significantly associated with adverse clinical outcomes (adjusted hazard ratio for composite CVD endpoints, 2.47; 95% confidence interval, 1.29-4.92; P = 0.006).Elevated levels of LR11 were significantly associated with long-term clinical outcomes among CAD patients treated with statins after first PCI.

Reducing Cardiovascular Disease Risk in Women Beyond Statin Therapy: New Insights 2020.

Management of residual and persistent cardiovascular disease (CVD) risk among statin-treated individuals has emerged as an important preventive strategy. The purpose of this article is to review the unique landscape of CVD in women and relevant prior prevention trials, and to discuss how the recent results of the Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT) might apply to the contemporary management of CVD risk among statin-treated women. Women have unique risk factors that may impact CVD and its prevention. Historically, women have been underrepresented in CVD trials, posing a challenge to development of clinical recommendations for women. Low-density lipoprotein cholesterol-targeting treatments have demonstrated CVD risk reduction, with comparable effects in both sexes. In contrast, triglyceride-lowering treatments (niacin, fenofibrate, and omega-3 fatty acids) have reported mixed findings for CVD risk reduction. Recent clinical trials of combination omega-3 fatty acids (docosahexaenoic acid/eicosapentaenoic acid [EPA]) have not found significant CVD risk reduction. The recently published REDUCE-IT study found that icosapent ethyl, an EPA-only omega-3 fatty acid, in combination with statins, significantly reduced CVD events in high-risk patients. The icosapent ethyl group had a significantly lower occurrence of the primary composite CVD endpoint (17.2%) than the placebo group (22.0%; hazard ratio 0.75; 95% confidence interval 0.68-0.83; p < 0.001). CVD risk reduction with icosapent ethyl treatment was comparable between women and men (p for interaction, 0.33). Data from REDUCE-IT suggest women benefit similarly to men with respect to icosapent ethyl, a novel therapy for prevention of CVD.

The Impact of APOL1 on Chronic Kidney Disease and Hypertension.

Essential hypertension is a clinical diagnosis based on the presence of an elevated systemic blood pressure on physical examination without a clear inciting cause. It has multiple etiologies and is not a homogeneous disorder. Hypertension contributes to the development and progression of atherosclerotic cardiovascular diseases, and antihypertensive treatment reduces the risk of fatal and nonfatal myocardial infarction, stroke, and congestive heart failure. Although hypertension is frequently present in nondiabetic individuals with low levels of proteinuria and chronic kidney disease, reducing blood pressures in this population does not reliably slow nephropathy progression. Many of these patients with recent African ancestry have the primary kidney disease "solidified glomerulosclerosis" that is strongly associated with renal-risk variants in the apolipoprotein L1 gene (APOL1). This kidney disease contributes to secondarily elevated blood pressures. The APOL1-associated spectrum of nondiabetic nephropathy also includes proteinuric kidney diseases, idiopathic focal segmental glomerulosclerosis, collapsing glomerulopathy, severe lupus nephritis, and sickle cell nephropathy. This article reviews relationships between mild to moderate essential hypertension and chronic kidney disease with a focus on the role of APOL1 in development of hypertension. Available evidence strongly supports that APOL1 renal-risk variants associate with glomerulosclerosis in African Americans, which then causes secondary hypertension, not with essential hypertension per se.