Implications of Five Different Risk Models In Primary Prevention Guidelines.

BACKGROUND: A lack of consensus exists across guidelines as to which risk model should be used for the primary prevention of cardiovascular disease (CVD). Our objective was to determine potential improvements in the number needed to treat (NNT) and number of events prevented (NEP) using different risk models in patients eligible for risk stratification. METHODS: A retrospective observational cohort was assembled from primary care patients in Ontario, Canada between January 1st, 2010, to December 31st, 2014 and followed for up to 5 years. Risk estimation was undertaken in patients 40-75 years of age, without CVD, diabetes, or chronic kidney disease using the Framingham Risk Score (FRS), Pooled Cohort Equations (PCEs), a recalibrated FRS (R-FRS), Systematic Coronary Risk Evaluation 2 (SCORE2), and the low-risk region recalibrated SCORE2 (LR-SCORE2). RESULTS: The cohort consisted of 47,399 patients (59% women, mean age 54). The NNT with statins was lowest for SCORE2 at 40, followed by LR-SCORE2 at 41, R-FRS at 43, PCEs at 55, and FRS at 65. Models that selected for individuals with a lower NNT recommended statins to fewer, but higher risk patients. For instance, SCORE2 recommended statins to 7.9% of patients (5-year CVD incidence 5.92%). The FRS, however, recommended statins to 34.6% of patients (5-year CVD incidence 4.01%). Accordingly, the NEP was highest for the FRS at 406 and lowest for SCORE2 at 156. CONCLUSIONS: Newer models such as SCORE2 may improve statin allocation to higher risk groups with a lower NNT but prevent fewer events at the population level.

Evaluating Readability, Understandability, and Actionability of Online Printable Patient Education Materials for Cholesterol Management: A Systematic Review.

BACKGROUND: Dyslipidemia management is a cornerstone in cardiovascular disease prevention and relies heavily on patient adherence to lifestyle modifications and medications. Numerous cholesterol patient education materials are available online, but it remains unclear whether these resources are suitable for the majority of North American adults given the prevalence of low health literacy. This review aimed to (1) identify printable cholesterol patient education materials through an online search, and (2) evaluate the readability, understandability, and actionability of each resource to determine its utility in practice. METHODS AND RESULTS: We searched the MEDLINE database for peer-reviewed educational materials and the websites of Canadian and American national health organizations for gray literature. Readability was measured using the Flesch-Kincaid Grade Level, and scores between fifth- and sixth-grade reading levels were considered adequate. Understandability and actionability were scored using the Patient Education Materials Assessment Tool and categorized as superior (>80%), adequate (50%-70%), or inadequate (<50%). Our search yielded 91 results that were screened for eligibility. Among the 22 educational materials included in the study, 15 were identified through MEDLINE, and 7 were from websites. The readability across all materials averaged an 11th-grade reading level (Flesch-Kincaid Grade Level=11.9±2.59). The mean±SD understandability and actionability scores were 82.8±6.58% and 40.9±28.60%, respectively. CONCLUSIONS: The readability of online cholesterol patient education materials consistently exceeds the health literacy level of the average North American adult. Many resources also inadequately describe action items for individuals to self-manage their cholesterol, representing an implementation gap in cardiovascular disease prevention.

Validation of the European SCORE2 models in a Canadian primary care cohort.

AIMS: Systematic Coronary Risk Evaluation Model 2 (SCORE2) was recently developed to predict atherosclerotic cardiovascular disease (ASCVD) in Europe. Whether these models could be used outside of Europe is not known. The objective of this study was to test the validity of SCORE2 in a large Canadian cohort. METHODS AND RESULTS: A primary care cohort of persons with routinely collected electronic medical record data from 1 January 2010 to 31 December 2014, in Ontario, Canada, was used for validation. The SCORE2 models for younger persons (YP) were applied to 57 409 individuals aged 40-69 while the models for older persons (OPs) were applied to 9885 individuals 70-89 years of age. Five-year ASCVD predictions from both the uncalibrated and low-risk region recalibrated SCORE2 models were evaluated. The C-statistic for SCORE2-YP was 0.74 in women and 0.69 in men. The uncalibrated SCORE2-YP overestimated risk by 17% in women and underestimated by 2% in men. In contrast, the low-risk region recalibrated model demonstrated worse calibration, overestimating risk by 100% in women and 36% in men. The C-statistic for SCORE2-OP was 0.64 and 0.62 in older women and men, respectively. The uncalibrated SCORE2-OP overestimated risk by more than 100% in both sexes. The low-risk region recalibrated model demonstrated improved calibration but still overestimated risk by 60% in women and 13% in men. CONCLUSION: The performance of SCORE2 to predict ASCVD risk in Canada varied by age group and depended on whether regional calibration was applied. This underscores the necessity for validation assessment of SCORE2 prior to implementation in new jurisdictions.

In this study, new tools [Systematic Coronary Risk Evaluation Model 2 (SCORE2)] that were developed across Europe to predict heart attack and stroke risk in healthy individuals were tested independently for the first time in a Canadian setting. Key findings are as follows:The accuracy of predictions from SCORE2 in Canadians depends on the age group considered and whether uncalibrated or recalibrated equations are being used.Independent assessment of tools such as SCORE2 remains useful prior to widespread implementation in new jurisdictions.

Development and Validation of the CANHEART Population-Based Laboratory Prediction Models for Atherosclerotic Cardiovascular Disease.

BACKGROUND: Prediction of atherosclerotic cardiovascular disease (ASCVD) in primary prevention assessments exclusively with laboratory results may facilitate automated risk reporting and improve uptake of preventive therapies. OBJECTIVE: To develop and validate sex-specific prediction models for ASCVD using age and routine laboratory tests and compare their performance with that of the pooled cohort equations (PCEs). DESIGN: Derivation and validation of the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) Lab Models. SETTING: Population-based cohort study in Ontario, Canada. PARTICIPANTS: A derivation and internal validation cohort of adults aged 40 to 75 years without cardiovascular disease from April 2009 to December 2015; an external validation cohort of primary care patients from January 2010 to December 2014. MEASUREMENTS: Age and laboratory predictors measured in the outpatient setting included serum total cholesterol, high-density lipoprotein cholesterol, triglycerides, hemoglobin, mean corpuscular volume, platelets, leukocytes, estimated glomerular filtration rate, and glucose. The ASCVD outcomes were defined as myocardial infarction, stroke, and death from ischemic heart or cerebrovascular disease within 5 years. RESULTS: Sex-specific models were developed and internally validated in 2 160 497 women and 1 833 147 men. They were well calibrated, with relative differences less than 1% between mean predicted and observed risk for both sexes. The c-statistic was 0.77 in women and 0.71 in men. External validation in 31 697 primary care patients showed a relative difference less than 14% and an absolute difference less than 0.3 percentage points in mean predicted and observed risks for both sexes. The c-statistics for the laboratory models were 0.72 for both sexes and were not statistically significantly different from those for the PCEs in women (change in c-statistic, -0.01 [95% CI, -0.03 to 0.01]) or men (change in c-statistic, -0.01 [CI, -0.04 to 0.02]). LIMITATION: Medication use was not available at the population level. CONCLUSION: The CANHEART Lab Models predict ASCVD with similar accuracy to more complex models, such as the PCEs. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research.

Sex differences in the association of sleep spindle density and cognitive performance among community-dwelling middle-aged and older adults with obstructive sleep apnea.

Recent studies have found associations between obstructive sleep apnea and cognitive decline. The underlying mechanisms are still unclear. Here, we investigate the associations between changes in micro-architecture, specifically sleep spindles, and cognitive function in community-dwelling middle-aged and older adults, some with obstructive sleep apnea, with a focus on sex differences. A total of 125 voluntary participants (mean age 66.0 ± 6.4 years, 64 females) from a larger cohort (participants of the Brain in Motion Studies I and II) underwent 1 night of in-home polysomnography and a neuropsychological battery (sleep and cognitive testing were conducted within 2 weeks of each other). A semi-automatic computerized algorithm was used to score polysomnography data and detect spindle characteristics in non-rapid eye movement Stages 2 and 3 in both frontal and central electrodes. Based on their apnea-hypopnea index, participants were divided into those with no obstructive sleep apnea (apnea-hypopnea index < 5 per hr, n = 21), mild obstructive sleep apnea (5 ≥ apnea-hypopnea index < 15, n = 47), moderate obstructive sleep apnea (15 ≥ apnea-hypopnea index < 30, n = 34) and severe obstructive sleep apnea (apnea-hypopnea index ≥ 30, n = 23). There were no significant differences in spindle characteristics between the four obstructive sleep apnea severity groups. Spindle density and percentage of fast spindles were positively associated with some verbal fluency measures on the cognitive testing. Sex might be linked with these associations. Biological sex could play a role in the associations between spindle characteristics and some verbal fluency measures. Obstructive sleep apnea severity was not found to be a contributing factor in this non-clinical community-dwelling cohort.

Guideline LDL-C Threshold Achievement in Acute Myocardial Infarction Patients: A Real-World Evidence Study Demonstrating the Impact of Treatment Intensification with PCSK9i.

INTRODUCTION: A high proportion of Canadian patients with acute myocardial infarction (AMI) do not achieve the threshold low-density lipoprotein cholesterol (LDL-C) levels recommended by the Canadian Cardiovascular Society in 2021. This increases the risk of subsequent atherosclerotic cardiovascular disease (ASCVD) events. Here, we assess LDL-C levels and threshold achievement among patients by lipid-lowering therapies (LLT) received post-AMI. METHODS: A retrospective cohort study of patients identified with AMI between 2015 and 2019 was conducted using administrative health databases in Alberta, Canada. Patients were grouped by their highest-intensity LLT post-AMI (proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) + another LLT; PCSK9i alone; ezetimibe + statin; statins (high, moderate, low intensity); or ezetimibe alone), and available LDL-C levels were examined in the year before and after LLT dispense date. RESULTS: The cohort included 15,283 patients. In patients on PCSK9i + LLT, the median [95% confidence interval (CI)] LDL-C levels decreased from 2.7 (2.3-3.4) before to 0.9 (0.5-1.2) mmol/l after treatment, the largest decrease among treatment groups. In the ezetimibe + statin and high-intensity statin groups, median (95% CI) values after treatment were 1.5 (1.5-1.6) and 1.4 (1.4-1.4) mmol/l, respectively. The proportion of patients below the 1.8 mmol/l threshold increased by 77.7% in the PSCK9i + LLT group after treatment, compared to 45.4 and 32.4% in the ezetimibe + statin and high-intensity statin groups, respectively. CONCLUSIONS: Intensification with PCSK9i in AMI patients results in a greater proportion of patients achieving below the recommended LDL-C threshold versus statins and or ezetimibe alone. Increased focus on achieving below the LDL-C thresholds with additional LLT as required may benefit patient cardiovascular outcomes.

Temporal Trends of the Prevalence of Angina With No Obstructive Coronary Artery Disease (ANOCA).

BACKGROUND: Angina with no obstructive coronary artery disease (ANOCA) is a common entity. There is still under-recognition of this condition, but it is unclear if the referral patterns for chest pain diagnosis have changed. We aimed to determine if the prevalence of patients diagnosed with ANOCA by means of coronary angiography has changed over time. METHODS: A population-based cohort of patients who had their first coronary angiogram for a chest pain syndrome in Alberta from 1995 to 2020 was extracted retrospectively from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) database. A temporal trend analysis was performed to compare patients with ANOCA vs obstructive coronary artery disease (CAD), and the predictors of ANOCA were investigated. RESULTS: In our analysis, 121,066 patients were included (26% ANOCA, 31% female, overall mean age 62 years). The percentages of ANOCA vs obstructive CAD ranged from 24.2% to 26.7% in all patients (P < 0.001), from 19.4% to 21.4% in patients with acute coronary syndromes (P = 0.002), and from 30.6% to 37.5% in patients with stable angina (P < 0.001). Independent predictors of ANOCA were female sex (odds ratio [OR] 3.34, 95% confidence interval [CI] 3.05-3.66), younger age (OR 0.96, 95% CI 0.95-0.96), history of atrial fibrillation (OR 2.18, 95% CI 1.73-2.73), and stable angina (vs myocardial infarction: OR 0.25, 95% CI 0.23-0.28; vs unstable angina: OR 0.79, 95% CI 0.70-0.89). Traditional cardiovascular risk factors were associated with obstructive CAD. CONCLUSIONS: There remained a high prevalence of ANOCA detected during invasive coronary angiography, which remained stable over time. This study demonstrates an opportunity to exclude obstructive CAD with less invasive testing, particularly in women.

Repurposing Metformin for Vascular Disease.

Metformin has been used as an oral anti-hyperglycaemic drug since the late 1950s; however, following the release in 1998 of the findings of the 20-year United Kingdom Prospective Diabetes Study (UKPDS), metformin use rapidly increased and today is the first-choice anti-hyperglycaemic drug for patients with type 2 diabetes (T2D). Metformin is in daily use by an estimated 150 million people worldwide. Historically, the benefits of metformin as an anti-diabetic and cardiovascular-protective drug have been linked to effects in the liver, where it acts to inhibit gluconeogenesis and lipogenesis, as well as reduce insulin resistance and enhance peripheral glucose utilization. However, direct protective effects on the endothelium and effects in the gut prior to metformin absorption are now recognized as important. In the gut, metformin modulates the glucagon-like peptide- 1 (GLP-1) - gut-brain axis and impacts the intestinal microbiota. As the apparent number of putative tissue and cellular targets for metformin has increased, so has the interest in re-purposing metformin to treat other diseases that include polycystic ovary syndrome (PCOS), cancer, neurodegenerative diseases, and COVID-19. Metformin is also being investigated as an anti-ageing drug. Of particular interest is whether metformin provides the same level of vascular protection in individuals other than those with T2D, including obese individuals with metabolic syndrome, or in the setting of vascular thromboinflammation caused by SARS-CoV-2. In this review, we critically evaluate the literature to highlight clinical settings in which metformin might be therapeutically repurposed for the prevention and treatment of vascular disease.

Chest Pain Evaluation: Diagnostic Testing.

Chest pain/discomfort (CP) is a common symptom and can be a diagnostic dilemma for many clinicians. The misdiagnosis of an acute or progressive chronic cardiac etiology may carry a significant risk of morbidity and mortality. This review summarizes the different options and modalities for establishing the diagnosis and severity of coronary artery disease. An effective test selection algorithm should be individually tailored to each patient to maximize diagnostic accuracy in a timely fashion, determine short- and long-term prognosis, and permit implementation of evidence-based treatments in a cost-effective manner. Through collaboration, a decision algorithm was developed (www.chowmd.ca/cadtesting) that could be adopted widely into clinical practice.

La douleur ou la gêne thoracique sont des symptômes fréquents qui peuvent poser un dilemme diagnostique pour de nombreux médecins. Les erreurs de diagnostic d'une cause aiguë ou chronique progressive d'origine cardiaque peuvent d'ailleurs entraîner un risque considérable de morbidité et de mortalité. La présente synthèse porte sur les différentes options et modalités d'établissement du diagnostic et de la gravité d'une coronaropathie. Un algorithme efficace pour le choix des tests doit être adapté à chaque patient afin de maximiser l'exactitude diagnostique dans les plus brefs délais, de déterminer le pronostic à court et à long terme, et de permettre une mise en œuvre de traitements fondés sur des données probantes tout en tenant compte des coûts. Un algorithme décisionnel a donc été conjointement mis au point (www.chowmd.ca/cadtesting) et pourrait être largement adopté dans la pratique clinique.

Magnetic Resonance Imaging of Intraplaque Hemorrhage and Plaque Lipid Content With Continued Lipid-Lowering Therapy: Results of a Magnetic Resonance Imaging Substudy in AIM-HIGH.

BACKGROUND: Intraplaque hemorrhage (IPH) is associated with plaque progression and ischemic events, and plaque lipid content (% lipid core) predicts the residual atherosclerotic cardiovascular disease risk. This study examined the impact of IPH on lipid content change in the setting of intensive lipid-lowering therapy. METHODS: In total, 214 AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low High-Density Lipoprotein/High Triglycerides: Impact on Global Health Outcomes) participants with clinically established ASCVD and low high-density lipoprotein cholesterol received cartoid MRI at baseline and 2 years to assess changes in carotid morphology and composition. Patients were randomized to extended-release niacin or placebo, and all received simvastatin with optional ezetimibe as necessary to lower low-density lipoprotein cholesterol to 40 to 80 mg/dL. Changes in lipid content and carotid morphology were tested using the Wilcoxon signed-rank test. Differences between subjects with and without IPH and between subjects assigned extended-release niacin or placebo were tested using the Wilcoxon rank-sum test. Linear regression was used to test the association of IPH and lipid content changes after adjusting for clinical risk factors. RESULTS: Among 156 patients (61±9 years; 81% men) with complete MRI, prior statin use: <1 year, 26%; 1 to 5 years, 37%; >5 years, 37%. Triglycerides and ApoB decreased significantly, whereas high-density lipoprotein cholesterol and ApoA1 increased significantly over time. Plaque lipid content was significantly reduced (-0.5±2.4 %/year, P = 0.017) without a significant difference between the 2 treatment groups. However, the lipid content increased in plaques with IPH but regressed in plaques without IPH (1.2±2.5 %/year versus -1.0±2.2, P = 0.006). Additionally, IPH was associated with a decrease in lumen area (-0.4±0.9 mm2/year versus 0.3±1.4, P = 0.033). IPH remained significantly associated with increase in lipid content in multivariable analysis (54.4%, 95% CI: 26.8, 88.0, P < 0.001). CONCLUSIONS: Carotid plaques under continued intensive lipid-lowering therapy moved toward stabilization. However, plaques with IPH showed greater increases in lipid content and greater decreases in lumen area than plaques without IPH. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01178320.

Population-Based Recalibration of the Framingham Risk Score and Pooled Cohort Equations.

BACKGROUND: The Framingham Risk Score (FRS) and Pooled Cohort Equations (PCEs) overestimate risk in many contemporary cohorts. OBJECTIVES: This study sought to determine if recalibration of these scores using contemporary population-level data improves risk stratification for statin therapy. METHODS: Five-year FRS and PCEs were recalibrated using a cohort of Ontario residents alive January 1, 2011, who were 30 to 79 years of age without cardiovascular disease. Scores were externally validated in a primary care cohort of routinely collected electronic medical record data from January 1, 2010, to December 31, 2014. The relative difference in mean predicted and observed risk, number of statins avoided, and number needed to treat with statins to reduce a cardiovascular event at 5 years were reported. RESULTS: The FRS was recalibrated in 6,938,971 Ontario residents (51.6% women, mean age 48 years) and validated in 71,450 individuals (56.1% women, mean age 52 years). Recalibration reduced overestimation from 109% to 49% for women and 131% to 32% for men. The recalibrated FRS was estimated to reduce statin prescriptions in up to 26 per 1,000 low-risk women and 80 per 1,000 low-risk men, as well as reduce the number needed to treat from 61 to 47 in women and from 53 to 41 in men. In contrast, after recalibration of the PCEs, risk remained overestimated by 217% in women and 128% in men. CONCLUSIONS: Recalibration is a feasible solution to improve risk prediction but is dependent on the model being used. Recalibration of the FRS but not the PCEs reduced overestimation and may improve utilization of statins.

Racial and Ethnic Differences in the Association Between Classical Cardiovascular Risk Factors and Common Carotid Intima-Media Thickness: An Individual Participant Data Meta-Analysis.

Background The major risk factors for atherosclerotic cardiovascular disease differ by race or ethnicity but have largely been defined using populations of European ancestry. Despite the rising prevalence of cardiovascular disease in Africa there are few related data from African populations. Therefore, we compared the association of established cardiovascular risk factors with carotid-intima media thickness (CIMT), a subclinical marker of atherosclerosis, between African, African American, Asian, European, and Hispanic populations. Methods and Results Cross-sectional analyses of 34 025 men and women drawn from 15 cohorts in Africa, Asia, Europe, and North America were undertaken. Classical cardiovascular risk factors were assessed and CIMT measured using B-mode ultrasound. Ethnic differences in the association of established cardiovascular risk factors with CIMT were determined using a 2-stage individual participant data meta-analysis with beta coefficients expressed as a percentage using the White population as the reference group. CIMT adjusted for risk factors was the greatest among African American populations followed by Asian, European, and Hispanic populations with African populations having the lowest mean CIMT. In all racial or ethnic groups, men had higher CIMT levels compared with women. Age, sex, body mass index, and systolic blood pressure had a significant positive association with CIMT in all races and ethnicities at varying magnitudes. When compared with European populations, the association of age, sex, and systolic blood pressure with CIMT was weaker in all races and ethnicities. Smoking (beta coefficient, 0.39; 95% CI, 0.09-0.70), body mass index (beta coefficient, 0.05; 95% CI, 0.01-0.08) and glucose (beta coefficient, 0.13; 95% CI, 0.06-0.19) had the strongest positive association with CIMT in the Asian population when compared with all other racial and ethnic groups. High-density lipoprotein-cholesterol had significant protective effects in African American (beta coefficient, -0.31; 95% CI, -0.42 to -0.21) and African (beta coefficient, -0.26; 95% CI, -0.31 to -0.19) populations only. Conclusions The strength of association between established cardiovascular risk factors and CIMT differed across the racial or ethnic groups and may be due to lifestyle risk factors and genetics. These differences have implications for race- ethnicity-specific primary prevention strategies and also give insights into the differential contribution of risk factors to the pathogenesis of cardiovascular disease. The greatest burden of subclinical atherosclerosis in African American individuals warrants further investigations.

Aerobic exercise training in older men and women-Cerebrovascular responses to submaximal exercise: Results from the Brain in Motion study.

Physical inactivity is a leading modifiable risk factor for cardiovascular and cerebrovascular disease, cognitive dysfunction, and global mortality. Regular exercise might mitigate age-related declines in cardiovascular and cerebrovascular function. In this study, we hypothesize that a 6-month aerobic exercise intervention will lead to a decrease in cerebrovascular resistance index (CVRi) and to an increase in cerebral blood flow (CBF) and cerebrovascular conductance index (CVCi) during two submaximal exercise workloads (40% VO2 max and 65 W), intensities that have been shown to be comparable to activities of daily life. Two hundred three low-active healthy men and women enrolled in the Brain in Motion study, completed a 6-month exercise intervention and underwent submaximal and maximal tests pre-/post-intervention. The intervention improved the gas exchange threshold and maximal oxygen consumption (VO2 max), with no change in heart rate at VO2 max, during the treadmill VO2 max test. Heart rate and CVRi decreased from pre-intervention values during both relative (40% VO2 max) and absolute (65 W) submaximal exercise tests. Blood flow velocity in the middle cerebral artery and CVCi increased post-intervention during 40% VO2 max and 65 W. Changes in mean arterial pressure were found only during the absolute component (65 W). Our study demonstrates that aerobic exercise improves not only cardiorespiratory indices but also cerebrovascular function at submaximal workloads which may help to mitigate age-related declines in everyday life. Investigation of the mechanisms underlying the decline in cardiovascular and cerebrovascular capacity with aging has important implications for the maintenance of health and continued independence of older adults.

Anti-Müllerian hormone and vascular dysfunction in women with chronic kidney disease.

Young women with chronic kidney disease (CKD) have disproportionately increased risk of cardiovascular mortality. Reduced anti-Müllerian hormone (AMH) is linked to poor cardiovascular outcomes in the general population, but whether AMH is associated with increased cardiovascular risk in the high-risk CKD population is unknown. This study examined the association between AMH and vascular function, validated markers of cardiovascular risk, in women with CKD. An exploratory cross-sectional study was performed in 47 young women with CKD. Laboratory measurements of AMH were collected. Using standardized protocols, endothelial function was measured with brachial artery flow-mediated dilation and hyperemic velocity time integral. Arterial stiffness was measured with aortic augmentation index and pulse wave velocity. Multivariate linear regression analyses were utilized to evaluate the association between AMH levels and each measure of vascular health. Forty women (36 ± 7 years) with non-dialysis-dependent CKD and 7 women (38 ± 6 years) with dialysis-dependent CKD participated. AMH levels were inversely associated with age (p = 0.01) but not associated with eGFR (p = 0.59) or dialysis status (p = 0.97). AMH was associated with brachial artery flow-mediated dilation (R2  = 0.21 [p = 0.03]) and aortic augmentation index (R2  = 0.20 [p = 0.04]) in the non-dialysis-dependent participants, and with aortic augmentation index in all participants (R2  = 0.18 [p = 0.03]). No association between AMH and any measure of vascular function was demonstrated in the dialysis-dependent participants. AMH levels are associated with impaired vascular function in young women with CKD and may be an important marker of future cardiovascular risk. Further investigation into this female-specific cardiovascular risk factor is warranted in this high-risk population.

Impact of intermittent hypoxia on human vascular responses during sleep.

Exposure to intermittent hypoxia (IH) ≥15 times per hour is believed to be the primary mechanism for the increased risk of cerebrovascular and cardiovascular disease in patients with moderate to severe sleep apnea. Human experimental models of IH used to investigate this link have been predominantly employed during wakefulness, which limits extrapolation of findings to sleep apnea where IH occurs during sleep. Moreover, how IH impacts vascular regulation during sleep has not been measured quantitatively. Therefore, the objective of this study was to assess the impact sleep accompanied by IH on vascular responses to hypoxia and hypercapnia during sleep. Ten males performed two randomly scheduled 6-h overnight sleep studies. One sleep study was performed in room air (normoxia) and the other sleep study was performed during isocapnic IH (60 s hypoxia-60 s normoxia). On each night, cerebrovascular (peak blood velocity through the middle cerebral artery (V¯P); transcranial Doppler ultrasound) and cardiovascular (blood pressure, heart rate) responses to hypoxia and hypercapnia were measured before sleep onset (PM-Awake), within the first 2 h of sleep (PM-Asleep), in the 5th (out of 6) hours of sleep (AM-Asleep) and after being awoken in the morning (AM-Awake). Sleep accompanied by IH had no impact on the V¯P and blood pressure responses to hypoxia and hypercapnic at any timepoint (p ≥ 0.103 for all responses). However, the AM-Awake heart rate response to hypoxia was greater following sleep in IH compared to sleep in normoxia. Independent of the sleep environment, the V¯P response to hypoxia and hypercapnia were reduced during sleep. In conclusion, cerebral blood flow responses are reduced during sleep compared to wakefulness, but 6 h of sleep accompanied by IH does not alter cerebrovascular and cardiovascular response to hypoxia and hypercapnia during wakefulness or sleep in healthy young humans. However, it is likely that longer exposure to IH during sleep (i.e., days-to-weeks) is required to better elucidate IH's impact on vascular regulation in humans.

Care gaps in achieving cholesterol targets in people with diabetes: A population-based study in a universal health care setting.

AIMS: Statins are first line therapy in people with diabetes. Little is known about real-world statin intensity use and low-density lipoprotein cholesterol (LDL-C) levels achieved. We aimed to describe statin intensity used, achievement of LDL-C targets, and factors associated with achieving targets among adults with diabetes. METHODS: This population based (∼4.3 million), retrospective observational study, used clinical and administrative databases. Statin use by intensity, adherence, and achievement of LDL-C targets in adults with diabetes were described. Multiple logistic regression assessed the factors associated with achieving targets. RESULTS: Out of 331,312 individuals with diabetes, 88% had an index LDL-C test. At follow up, 31% overall did not achieve LDL-C targets and overall adherence was 66%. Failure to achieve targets was 49%, 30%, and 25% in low-, moderate-, and high-intensity statin groups, respectively. Those who were older, males, had a history of myocardial infarction, stroke, congestive heart failure, renal disease, better adherence, and higher intensity statin users were more likely to achieve targets. CONCLUSIONS: One-third of people on statins did not achieve targets. Strategies to fill the gap between ideal and current levels of LDL-C achieved are needed if the benefits of statins demonstrated in trials are to be translated into practice.

Cardiac remodelling predicts outcome in patients with chronic heart failure.

AIMS: Surveillance imaging is often used to detect remodelling, a change in cardiac geometry, and/or function; however, there are limited data in patients with chronic heart failure (HF). We sought to characterize cardiac remodelling in patients with chronic HF and evaluate its association with outcome. METHODS AND RESULTS: A prospective cohort of patients at risk for HF or with chronic HF underwent cardiac magnetic resonance (CMR) at baseline and 1 year. Ventricular function, volumes, mass, left atrial volume, global longitudinal strain, and myocardial scar were measured. The primary outcome was a composite of death or cardiovascular hospitalization up to 5 years from the 1 year scan. Cox regression was used to identify 1 year CMR predictors of outcome after adjusting for baseline risk. A total of 262 patients (median age 68 years, 57% males) including 96 at risk for HF, 97 with HF and preserved ejection fraction, and 69 with HF and reduced ejection fraction were included. In the patients with HF, 55 events were identified during follow-up. After adjustment for baseline clinical risk, Cox proportion hazard regressions only identified 1 year change in left ventricular (LV) mass index as a CMR predictor of outcome, adjusted hazard ratio 1.21 (1.02, 1.44) per 10% increase, P = 0.031. Cardiac remodelling defined as a 1 year change in LV mass index ≥15% was observed in 35% of patients with HF. Patients with adverse remodelling of LV mass index had more events on Kaplan-Meier analyses compared to those with no remodelling, log-rank P = 0.004 for overall cohort, P = 0.035 for heart failure with preserved ejection fraction and P = 0.035 for heart failure and reduced ejection fraction. CONCLUSIONS: Cardiac remodelling is common during serial CMR assessment of patients with chronic HF. Change in LV mass predicted long-term outcomes whereas change in left ventricular ejection fraction did not.