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.

Laboratory reporting of framingham risk score increases statin prescriptions in at-risk patients.

BACKGROUND: The under-utilization of cardiovascular preventative therapy with statins warrants novel interventions to optimize prescriptions in at-risk patients. We investigated the role of a laboratory generated Framingham Risk Score (FRS) provided to primary care clinicians in changing statin use in a primary care setting. METHODS: Data was acquired from the electronic medical records of 1573 anonymized patients undergoing routine lipid testing. Follow-up statin use and low-density lipoprotein cholesterol levels were obtained for 2 years post intervention. FRS parameters were entered into a laboratory information system, and provided to ordering physicians along with the cholesterol profile and the appropriate current Canadian Dyslipidemia treatment recommendation in a single report. Statin prescription rates following the intervention were compared with historical use 6 months prior to the study. RESULTS: A total of 1283 participants (mean age of 60 ± 11 years) had an FRS report and were considered for analysis. Two hundred individuals filled a statin prescription in the 6 months prior to their index lipid test, and an additional 84 filled a statin prescription following the intervention (42% increase). The relative and absolute increase in statin prescription was 47.3% and 13.6% in the high-risk group p < 0.001, 53.3% and 8.1% in the intermediate-risk group p < 0.001, and 17.0% and 1.42% in the low-risk group p = 0.008, respectively. CONCLUSION: The use of the laboratory reported FRS was associated with a significant increase in the rate of statin prescription across all risk groups. The expansion of FRS reporting across other health regions would improve cardiovascular risk prevention.

Patterns of Left-Ventricular Function Assessment in Patients With Acute Coronary Syndromes.

BACKGROUND: In patients with acute coronary syndromes (ACS), guidelines recommend the assessment of left-ventricular ejection fraction (LVEF). Many patients with ACS undergo multiple assessments of LVEF, the clinical value of which is unknown. METHODS: Patients with ACS undergoing cardiac catheterization between 2012 and 2016 were evaluated and assessments of LV function identified. To evaluate changes in LVEF over time, available echocardiograms were reviewed in a subsample of patients with LVEF data available (n = 3221). Patients with ACS were classified into 3 groups: group 1 (LVEF > 50%), group 2 (LVEF 35% to 50%), and group 3 (LVEF < 35%). RESULTS: Our cohort consisted of 8327 patients with ACS (76% men), presenting with a mean age of 62.4 ± 12.4 years. At index presentation, 66% of patients had an LVEF > 50%, 27% had an LVEF between 35% and 50%, and 7% had severely reduced LVEF of < 35%. More than half of the cohort (n = 4600) had follow-up assessment of LV function, performed over an average of 2.71 ± 1.31 years. In the subsample of 3221 patients, only 1.1% of those in group 1, and 5.1% of those in group 2, deteriorated to an LVEF < 35%. CONCLUSIONS: Patients with ACS often undergo multiple assessments of LV function. Those with initially preserved EF rarely demonstrate a decline in EF to < 35%. A reduction in low-value cardiac tests may be an important first step in improving the quality of care for patients with ACS.

CONTEXTE: En cas de syndrome coronarien aigu (SCA), les lignes directrices recommandent d'évaluer la fraction d'éjection ventriculaire gauche (FEVG). Beaucoup de patients présentant un SCA subissent plusieurs évaluations de la FEVG, une pratique dont on ne connaît pas la valeur clinique. MÉTHODOLOGIE: Nous avons examiné les dossiers de patients atteints d'un SCA ayant subi un cathétérisme cardiaque entre 2012 et 2016 afin de relever les évaluations de la fonction ventriculaire gauche. Pour évaluer l'évolution de la FEVG au fil du temps, nous avons examiné les échocardiogrammes d'un sous-échantillon de patients pour lesquels des données sur la FEVG étaient disponibles (n = 3 221). Les patients présentant un SCA ont été divisés en trois groupes : groupe 1 (FEVG > 50 %), groupe 2 (FEVG de 35 à 50 %) et groupe 3 (FEVG < 35 %). RÉSULTATS: Notre cohorte comprenait 8 327 patients présentant un SCA (proportion d'hommes : 76 %), dont l'âge moyen était de 62,4 ± 12,4 ans. Au moment de la manifestation de référence, 66 % des patients avaient une FEVG > 50 %, 27 %, une FEVG de 35 à 50 % et 7 %, une FEVG gravement réduite < 35 %. Plus de la moitié des patients de la cohorte (n = 4 600) ont subi une évaluation de suivi de la fonction ventriculaire gauche, effectuée sur une période de 2,71 ± 1,31 ans en moyenne. Dans le sous-échantillon de 3 221 patients, seulement 1,1 % des patients du groupe 1 et 5,1 % de ceux du groupe 2 ont vu leur FEVG se détériorer à une valeur < 35 %. CONCLUSIONS: Les patients présentant un SCA subissent souvent plusieurs évaluations de la fonction ventriculaire gauche. Ceux dont la fraction d'éjection était initialement préservée ont rarement présenté une réduction de la fraction d'éjection en deçà de 35 %. Une réduction du nombre d'évaluations cardiaques offrant peu de valeur pourrait constituer un premier pas important vers l'amélioration de la qualité des soins prodigués aux patients présentant un SCA.

Association of Apolipoproteins B and A-1 With Markers of Vascular Health or Cardiovascular Events.

BACKGROUND: Apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1) are markers of lipoprotein metabolism. Although their relationship to cardiovascular disease has been well documented, little is known regarding their correlation to measures of vascular structure and function. This study was conducted to investigate the relationship between apoA-1, apoB, and measures of vascular function, as well their relationship to adverse cardiovascular events. Moreover, we evaluated whether apoB or the apoB/apoA-1 ratio was more closely related to vascular markers than was low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C). METHODS: One thousand five hundred twenty-two healthy middle-aged men of the Firefighters and Their Endothelium (FATE) cohort were assessed for risk factors and flow-mediated dilatation (FMD), hyperemic velocity (VTI), and carotid intima-media thickness (CIMT). Participants were then followed for 7.2 ± 1.7 years. ApoA-1 and apoB levels were measured at baseline. RESULTS: ApoA-1 was not correlated with VTI, FMD, or CIMT, whereas apoB was significantly related to VTI and CIMT. Multiple regression analyses confirmed apoB as being related to both VTI (ß = -0.083; P = 0.001) and CIMT (ß = 0.055; P = 0.022) in models adjusted for age; blood pressure; high-density lipoprotein C (HDL-C), triglyceride and insulin levels; waist circumference; and C-reactive protein levels. In substituted models, LDL-C (ß = -0.092; P < 0.001) and non-HDL-C (ß = -0.089; P = 0.001) levels appeared to have the same degree of association as apoB for VTI but were not associated with CIMT. ApoB was found to be associated with cardiovascular events (hazard ratio, 1.349; 95% confidence interval, 1.073-1.695; P = 0.010). CONCLUSIONS: ApoB had an independent but weak relationship with indices of microvascular health. Nevertheless, it was associated with occurrence rates of adverse cardiovascular events.

Association of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) With Cardiovascular Risk in Primary Prevention.

OBJECTIVE: Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the modulation of low-density lipoprotein metabolism. This study was conducted to evaluate the relationship between serum PCSK9 concentrations and measures of vascular health, subclinical atherosclerosis, and adverse cardiovascular events. The relationship between traditional risk factors and PCSK9 concentrations was also examined. APPROACH AND RESULTS: The cohort consisted of 1527 middle-aged men enrolled in the Firefighters and Their Endothelium (FATE) study, who were free of vascular disease and followed up over a mean period of 7.2±1.7 years. Baseline evaluation included assessment of traditional cardiovascular risk factors and measurements of flow-mediated dilation, reactive hyperemic velocity time integral, and carotid intima-media thickness. Biochemical parameters, including serum PCSK9 concentrations, were analyzed to determine predictors of vascular measures and to evaluate the role of PCSK9 in the occurrence of adverse cardiovascular events. Multivariate linear regression analyses indicated that body mass index, insulin, low-density lipoprotein-cholesterol, and triglycerides were independent predictors of PCSK9. Further modeling revealed no correlation between PCSK9 concentration and carotid intima media thickness, flow-mediated dilation, or reactive hyperemic velocity time integral. Analyses indicated no significant association between PCSK9 concentrations and cardiovascular event occurrences. CONCLUSIONS: Although correlated with low-density lipoprotein-cholesterol, insulin, and triglycerides, PCSK9 was not associated with measures of vascular function or structure. There was also no significant relationship between PCSK9 concentrations and cardiovascular events. Thus, although PCSK9 is an important therapeutic target to reduce circulating low-density lipoprotein-cholesterol concentrations, it is unlikely to be a biomarker of atherosclerotic risk or vascular health.

Microvascular dysfunction in schizophrenia: a case-control study.

BACKGROUND: Schizophrenia is a mental illness associated with cardiovascular disease at a younger age than in the general population. Endothelial dysfunction has predictive value for future cardiovascular events; however, the impact of a diagnosis of schizophrenia on this marker is unknown. AIMS: We tested the hypothesis that subjects with schizophrenia have impaired endothelial function. METHODS: A total of 102 subjects (34.5±7.5 years) participated in this study. This sample consisted of 51 subjects with a diagnosis of schizophrenia and 51 healthy subjects, who were matched for age (P=0.442), sex (P>0.999), and smoking status (P=0.842). Peripheral artery microvascular and conduit vessel endothelial function was measured using hyperemic velocity time integral (VTI), pulse arterial tonometry (PAT), and flow-mediated dilation (FMD). RESULTS: Significantly lower values of VTI were noted in subjects with schizophrenia (104.9±33.0 vs. 129.1±33.8 cm, P<0.001), whereas FMD (P=0.933) and PAT (P=0.862) did not differ between the two groups. A multivariable-linear-regression analysis, built on data from univariate and partial correlations, showed that only schizophrenia, sex, lipid-lowering medications, antihypertensive medications, and low-density lipoprotein (LDL)-cholesterol were predictive of attenuated VTI, whereas age, ethnicity, family history of cardiovascular disease, smoking status, systolic blood pressure, waist circumference, HDL-cholesterol, triglycerides, C-reactive protein, and homeostatic model assessment-insulin resistance (HOMA-IR), antidiabetic medications, antidepressant medications, mood stabilizers, benzodiazepines, and anticholinergic medications did not predict VTI in this model (adjusted R (2)=0.248). CONCLUSIONS: Our findings suggest that a diagnosis of schizophrenia is associated with impaired microvascular function as indicated by lower values of VTI, irrespective of many other clinical characteristics. It might be an early indicator of cardiovascular risk in schizophrenia, and might help to identify high-risk individuals.

The optimal measure of microvascular function with velocity time integral for cardiovascular risk prediction.

Recent evidence suggests that microvascular function may be important in cardiovascular risk prediction. One measure of microvascular function is hyperaemic velocity time integral (VTI). We assessed whether the VTI of more than one beat of reactive hyperaemia would provide a stronger correlate to traditional cardiovascular risk factors using a subset of subjects from the Firefighters and Their Endothelium (FATE) study. Vascular function was assessed by measurement of hyperaemic blood velocity with high-resolution ultrasound of the brachial artery. We evaluated three measures in the current analysis: the VTI of the first beat, average VTI of 10 beats, and maximum VTI of 10 beats post-cuff release. A total of 399 male subjects (45.5 ± 10 years) were included in this analysis. Univariate correlations between the three end points and cardiovascular risk factors were calculated, and multivariable regression models constructed. Intra-observer variability was approximately equal for all VTI end points (coefficient of variation: first = 1.6%, average = 1.4%, maximum = 1.4%). Univariate correlations between VTI and cardiovascular risk factors were similar across all three end points. In multivariable analyses, there were no differences in the relationships between cardiovascular risk factors and the various VTI end points (R(2) from 0.090 to 0.102). Age, systolic blood pressure, and BMI were predictors of the three VTI end points (p < 0.05). In conclusion, the first beat of reactive hyperaemia remains the suitable measure of microvascular function.

Microvascular function predicts cardiovascular events in primary prevention: long-term results from the Firefighters and Their Endothelium (FATE) study.

BACKGROUND: Biomarkers of atherosclerosis may refine clinical decision making in individuals at risk of cardiovascular disease. The purpose of the study was to determine the prognostic significance of endothelial function and other vascular markers in apparently healthy men. METHODS AND RESULTS: The cohort consisted of 1574 men (age, 49.4 years) free of vascular disease. Measurements included flow-mediated dilation and its microvascular stimulus, hyperemic velocity, carotid intima-media thickness, and C-reactive protein. Cox proportional hazard models evaluated the relationship between vascular markers, Framingham risk score, and time to a first composite cardiovascular end point of vascular death, revascularization, myocardial infarction, angina, and stroke. Subjects had low median Framingham risk score (7.9%). Cardiovascular events occurred in 71 subjects (111 events) over a mean follow-up of 7.2±1.7 years. Flow-mediated dilation was not associated with subsequent cardiovascular events (hazard ratio, 0.92; P=0.54). Both hyperemic velocity (hazard ratio, 0.70; 95% confidence interval, 0.54 to 0.90; P=0.006) and carotid intima-media thickness (hazard ratio, 1.45; confidence interval, 1.15 to 1.83; P=0.002) but not C-reactive protein (P=0.35) were related to events in a multivariable analysis that included Framingham risk score (per unit SD). Furthermore, the addition of hyperemic velocity to Framingham risk score resulted in a net clinical reclassification improvement of 28.7% (P<0.001) after 5 years of follow-up in the intermediate-risk group. Overall net reclassification improvement for hyperemic velocity was 6.9% (P=0.24). CONCLUSIONS: In men, hyperemic velocity, the stimulus for flow-mediated dilation, but not flow-mediated dilation itself was a significant risk marker for adverse cardiovascular outcomes. The prognostic value was additive to traditional risk factors and carotid intima-media thickness. Hyperemic velocity, a newly described marker of microvascular function, is a novel tool that may improve risk stratification of lower-risk healthy men.

Relationship between brachial artery flow-mediated dilatation, hyperemic shear stress, and the metabolic syndrome.

Metabolic syndrome (MetSyn) may predispose to cardiovascular disease (CVD) by causing vascular dysfunction. This study aimed to determine the association of MetSyn with vascular function, as assessed by brachial artery flow-mediated dilatation (FMD) and hyperemic shear stress (HSS). A total of 1,417 male firefighters without established diabetes and CVD were classified for MetSyn, according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP) definition. MetSyn was present in 267 individuals (19%). Although FMD was lower in those with versus without MetSyn (8.1 +/- 4.1 vs 8.7 +/- 4.0%; p = 0.02), this was not significant after adjusting for baseline differences (age, smoking, and brachial artery diameter) (p = 0.2). However, HSS was significantly lower in those with versus without MetSyn (72.0 +/- 27.8 vs 80.9 +/- 24.8 dyne/cm(2); p < 0.001), and there was a significant inverse graded relationship with the number of NCEP criteria present (mean HSS for those with 0, 1, 2, 3, 4, and 5 criteria: 83.2 +/- 22.5, 82.2 +/- 24.7, 76.5 +/- 27.2, 74.3 +/- 27.4, 66.5 +/- 28.4, 67.1 +/- 27.6 dyne/cm(2); p < 0.001 for trend). The individual NCEP criteria of abdominal obesity, systolic hypertension, and impaired fasting glucose were independent predictors for HSS. In conclusion, MetSyn was not associated with impaired FMD. Alternatively, HSS, a measure of microvascular function, was significantly lower in those with MetSyn. Thus, MetSyn may contribute to CVD by causing microvascular dysfunction.

Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C-reactive protein in healthy individuals.

AIMS: The present study was designed to (a) examine the interrelationship between endothelial function and CRP in healthy individuals and (b) evaluate the relationship of each biomarker towards global Framingham risk scores. METHODS AND RESULTS: Brachial artery flow-mediated vasodilatation (FMD), CRP, and traditional cardiovascular risk factors were measured in the Firefighters and Their Endothelium (FATE) study, which recruited 1154 male participants (mean age 47.4+/-9.8 years) with no known history of cardiovascular disease. No relationship was observed between FMD and CRP (p = 0.96). FMD and the Framingham risk score tended to correlate but not significantly (p = 0.07). A lower FMD was related to a higher systolic and diastolic blood pressure (p < 0.001 and p = 0.002, respectively) in the univariate analysis, and higher systolic blood pressure (p = 0.001) in the multivariate analysis. Elevated CRP levels independently correlated most closely with overall Framingham risk score (r = 0.36, p < 0.001) and a weaker although statistically significant relationship was seen with individual traditional cardiovascular risk factors (p < 0.005). CONCLUSIONS: The current study provided evidence that brachial artery FMD had no relationship to CRP in a large cohort of healthy subjects. These observations suggest that the predictive value of CRP may be largely independent of abnormalities in endothelial function. The additive prognostic value of endothelial vasodilator testing remains to be established.