Sleep apnea and retinal signs in cardiovascular disease: the Multi-Ethnic Study of Atherosclerosis

Purpose

The aim of the study was to examine the relationship between sleep apnea, retinal vascular caliber and retinopathy, and their impact on cardiovascular disease (CVD) risk.

Methods

A multi-ethnic cohort of 5,803 participants was examined based on standardized grading of retinal vascular caliber and retinopathy from digital fundus photographs, self-reported physician-diagnosed sleep apnea (PDSA), and incident cardiovascular events.

Results

In women, PDSA was associated with narrower arterioles (regression coefficient [β] ?5.76; 95 % confidence Interval [CI] ?8.51, ?3.02) after adjusting for cardio-metabolic risk factors. The incident rate ratio (IRR) of CVD was also associated with narrower arterioles (IRR for highest versus lowest tertile 1.91; 95 % CI 1.08, 3.38). In men, PDSA was not associated with arteriolar caliber. However, incident CVD was associated with narrower arterioles (IRR 1.67; 95 % CI 1.10, 2.52), wider venules (IRR 1.71; 95 % CI 1.13, 2.59) and PDSA (IRR 2.03, 95 % CI 1.17, 3.51). The IRR of CVD in men with PDSA increased minimally to 2.06 (95 % CI 1.18, 3.56) after adjustment for retinal arteriolar and venular caliber. Combining women and men, the IRR of CVD was 3.41 (95 % CI 1.79, 6.50) in those with both PDSA and narrower retinal arterioles.

Conclusions

Sleep apnea was associated with narrower retinal arterioles in women but not in men. However, sleep apnea was also associated with incident CVD in men. These suggest potential gender differences in susceptibility to microvascular disease in association with sleep apnea.

     

Differential association of retinal arteriolar and venular caliber with diabetes and retinopathy

Aims

To describe the relationship of retinal arteriolar and venular caliber with diabetes, retinopathy and hyperglycemia, in an Asian Indian population.

Methods

This was a population-based cross-sectional study of 3400 (75.6% response rate) Singapore ethnic Indians aged 40-80 years. Central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) were obtained using a validated computer-assisted program. Diabetes mellitus was identified using standardized criteria. Diabetic retinopathy was graded based on the modified Airlie House Classification System.

Results

There were 980 (32.2%) participants with diabetes. Of these, 327 (33.4%) had diabetic retinopathy. After multivariate adjustment, diabetic persons had a wider CRAE (145.23 μm vs 142.38 μm, P < 0.001). This relationship was stronger in persons without hyperlipidemia (P-interaction < 0.1). Among diabetic participants, wider CRVE was related to increasing severity of retinopathy (P for trend < 0.05) and this association may be altered by hypertensive status. Retinal arteriolar caliber widened with increasing glucose (P < 0.001) and HbA1C (P < 0.001) levels.

Conclusions

In Indian adults, wider retinal arteriolar caliber is associated with diabetes and hyperglycemia, while wider retinal venular caliber is associated with diabetic retinopathy. This is consistent with white populations and confirms the differential systemic association of retinal vascular caliber in Asian Indians.     

Retinal vascular geometry in Asian persons with diabetes and retinopathy

Purpose

Our purpose was to examine the relationship of retinal vascular parameters with diabetes and retinopathy in an older Asian population.

Methods

Retinal photographs from participants of a population-based survey of Asian Malay persons aged 40–80 years were analyzed. Specific retinal vascular parameters (tortuosity, branching angle, fractal dimension, and caliber) were measured using a semiautomated computer-based program. Diabetes was defined as random plasma glucose ≥ 11.1 mmol/liter, the use of diabetes medication, or physician-diagnosed diabetes. Retinopathy signs were graded from photographs using the modified Airlie House classification system.

Results

A total of 2735 persons were included in the study. Persons with diabetes (n = 594) were more likely to have straighter (less tortuous) arterioles and wider arteriolar and venular caliber than those without diabetes (n = 2141). Among subjects with diabetes, those with retinopathy had wider venular caliber than those without retinopathy (211.3 versus 204.9 mm, p = .001). Among nondiabetic subjects, however, those with retinopathy had more tortuous venules than those without retinopathy [5.19(×10⁴) versus 4.27(×10⁴), p < .001].

Conclusions

Retinal vascular parameters varied by diabetes and retinopathy status in this older Asian cohort. Our findings suggest that subtle alterations in retinal vascular architecture are influenced by diabetes.     

Retinal microvascular calibre and risk of incident diabetes: the multi-ethnic study of atherosclerosis

Aim

To prospectively examine the association of retinal microvascular signs with incident diabetes and impaired fasting glucose (IFG) in a multi-ethnic population-based cohort.

Methods

The multi-ethnic study of atherosclerosis comprised Caucasians, African-Americans, Hispanics and Chinese aged 45-84 years. Retinal vascular calibre and retinopathy were quantified from baseline retinal photographs. Incident diabetes and IFG were ascertained prospectively.

Results

After a median follow-up of 3 years, 243 (4.9%) people developed diabetes and 565 (15.0%) developed IFG. After adjusting for known risk factors, participants with wider retinal arteriolar calibre had a higher risk of developing diabetes [HR: 1.60; 95% CI: 1.12-2.29, p = 0.011 comparing highest with lowest arteriolar calibre tertile]. In ethnic subgroup analysis, the association between wider retinal arteriolar calibre and incident diabetes was stronger and statistically significant only in Caucasians [HR: 2.78; 95% CI: 1.37-5.62, p = 0.005]. Retinal venular calibre and retinopathy signs were not related to risk of diabetes or IFG.

Conclusion

Wider retinal arteriolar calibre is independently associated with an increased risk of diabetes, supporting a possible role for early arteriolar changes in diabetes development. This effect was largely seen in Caucasians, and not in other ethnic groups, and may reflect ethnic differences in susceptibility to diabetes from microvascular pathways.     

Retinal vascular caliber and metabolic syndrome in a Chinese population

Background: Microvascular changes have been associated with the metabolic syndrome. Methods: We included 869 participants aged ≥40 years from the High‐risk for Diabetes Changfeng Study, who had gradable fundus photographs. On digital photographs sum retinal arteriolar and venular calibers were measured with a semi‐automated system. Metabolic syndrome was defined according to the International Diabetes Federation consensus. Results: A total of 286 (32.9%) participants was diagnosed with metabolic syndrome. Participants with narrower retinal arteriolar caliber were more often diagnosed with metabolic syndrome (odds ratio 1.78, 95% confidence interval 1.02–3.10; lowest vs highest quintile). Additionally adjusting for age, gender, education, smoking and weekly activity, and adding arteriolar and venular caliber simultaneously in the same models did not alter these associations. In the component analyses, participants with narrower retinal arteriolar caliber were more likely to have central obesity, dyslipidaemia or raised blood pressure, and less likely to have raised fasting plasma glucose. The association between wider venular caliber and metabolic syndrome was less pronounced and non‐significant (odds ratio 1.34; 95% confidence interval 0.79–2.38; highest vs lowest quintile). Conclusion: Retinal arteriolar narrowing and, to a lesser extent, retinal venular dilatation were associated with metabolic syndrome in this Chinese population. These vascular changes, although small in magnitude, may still be important in the pathophysiological mechanisms involved in the metabolic syndrome.     

Value of coronary artery calcium score to predict severity or complexity of coronary artery disease

Background

Prediction of severity or complexity of coronary artery disease (CAD) is valuable owing to increased risk for cardiovascular events. Although the association between total coronary artery calcium (CAC) score and severity of CAD, Gensini score was not used, it has been previously demonstrated. There is no information about the association between total CAC score and complexity of CAD.

Objectives

To investigate the association between severity or complexity of coronary artery disease (CAD) assessed by Gensini score and SYNTAX score (SS), respectively, and coronary artery calcium (CAC) score, which is a noninvasive method for CAD evaluation in symptomatic patients with accompanying significant CAD.

Methods

Two-hundred-fourteen patients were enrolled. Total CAC score was obtained before angiography. Severity and complexity of CAD was assessed by Gensini score and SS, respectively. Associations between clinical and angiographic parameters and total CAC score were analyzed.

Results

Median total CAC score was 192 (23.0-729.8), and this was positively correlated with both Gensini score (r: 0.299, p<0.001) and SS (r: 0.577, p<0.001). At multivariate analysis, it was independently associated with age (ß: 0.154, p: 0.027), male gender (ß: 0.126, p: 0.035) and SS (ß: 0.481, p< 0.001). Receiver-operating characteristic (ROC) curve analysis revealed a cut-off value > 809 for SS >32 (high SS tertile).

Conclusion

In symptomatic patients with accompanying significant CAD, total CAC score was independently associated with SS and patients with SS >32 may be detected through high Agatston score.     

Low birthweight is associated with narrower arterioles in adults

Low birthweight is associated with increased risk of hypertension, but underlying mechanisms are obscure. We hypothesized structural microvascular alterations may be one such mechanism. We examined the association of birthweight and retinal arteriolar caliber in 3800 persons aged 51 to 72 years participating in a population-based study in 4 US communities (the Atherosclerosis Risk in Communities study). Participants reported full-term birth and their birthweight and had retinal photography. Retinal arteriolar and venular calibers were measured from digitized retinal photographs using a validated computer-assisted method. Lower birthweight was associated with narrower retinal arteriolar caliber, with each kg lower birthweight associated with 2.4 mum (95% confidence intervals, 1.3 to 3.5, P<0.001) narrower retinal arteriolar caliber, after controlling for age, gender, race, education, smoking, alcohol consumption, adult body mass index, and height. Additional adjustment for blood pressure averaged over the past 6 years and fasting glucose did not alter these findings, with each kg lower birthweight associated with a 1.7 mum (95% confidence intervals, 0.7 to 2.8, P<0.001) narrower retinal arteriolar caliber. This association was also present in persons without hypertension or diabetes. Lower birthweight was not associated with retinal venular caliber. These findings provide evidence that structural alterations in the arteriolar microcirculation may be a potential mechanism linking restricted fetal growth with subsequent risk of hypertension.     

Aortic distensibility and retinal arteriolar narrowing: the multi-ethnic study of atherosclerosis

Increased aortic stiffness and retinal arteriolar narrowing are subclinical vascular effects of chronic hypertension and predict future cardiovascular events. The relationship between these 2 vascular measures is uncertain and is examined in the Multi-Ethnic Study of Atherosclerosis. This cross-sectional analysis involves 3425 participants (aged 45 to 85 years) free of clinical cardiovascular disease. Retinal vascular caliber was quantified from digital retinal photographs using standardized protocols. Aortic distensibility was determined from chest MRI. After controlling for age, squared age, gender, race, study center, height, weight, heart rate, cigarette smoking, past and current systolic blood pressure, use of antihypertensive medications, diabetes, fasting glucose, lipid profile, and C-reactive protein, reduced aortic distensibility (first versus fourth distensibility quartile) was associated with increased odds of retinal arteriolar narrowing (odds ratio: 1.72; 95% CI: 1.15 to 2.58, comparing lowest to highest quartile of arteriolar caliber). Further adjustments for atherosclerotic measures (carotid intima-media thickness, coronary calcium score, and ankle brachial index) had minimal impact on this association (odds ratio: 1.70; 95% CI: 1.13 to 2.55). Reduced aortic distensibility was not associated with retinal venular caliber. We conclude that increased aortic stiffness is associated with retinal arteriolar narrowing, independent of measured blood pressure levels and vascular risk factors. These data suggest that changes in the microvasculature may play a role linking aortic stiffness with clinical cardiovascular events.     

Are Retinal Microvascular Caliber Changes Associated with Severity of Coronary Artery Disease in Symptomatic Cardiac Patients?

Objectives: Recent population‐based studies have shown that retinal vascular caliber may predict the risk of clinical coronary artery disease (CAD) events. Whether this association is related to macro‐ or microvascular mechanisms remains unknown. We investigated the relationship of retinal vascular caliber with severity and extent of CAD in symptomatic cardiac patients. Materials and Methods: Overall, 98 patients attending diagnostic coronary angiography were recruited. Coronary angiography was used to assess for the severity and extent of CAD. Digital retinal photography was performed immediately prior to cardiac catheterization, and retinal vascular caliber was measured from these photographs by using a computer program and summarized as central retinal arteriolar (CRAE) and venular (CRVE) equivalents. Results: Retinal arteriolar and venular calibers were not associated with increasing severity of CAD, as assessed by Leaman scores (CRAE/CRVE: P for trend=0.17/0.57), presence of clinically significant CAD (CRAE/CRVE: P=0.35/0.32), or number of diseased vessels (CRAE/CRVE: P for trend=0.18/0.69). Conclusions: Retinal vascular caliber changes are not associated with the severity of obstructive CAD in symptomatic patients. These data suggest that the association of retinal vascular caliber with clinical CAD seen in epidemiological studies may not be applicable to clinical symptomatic patients and may be related to microvascular, rather than macrovascular, mechanisms.     

Association between HMW adiponectin,HMW-total adiponectin ratio and early-onset coronary artery disease in Chinese population

Objective

Adiponectin is an adipose-secreting protein that shows atheroprotective property and has inverse relation with coronary artery disease (CAD). High-molecular weight (HMW) adiponectin is reported as the active form of adiponectin. In the present study, we aimed to investigate the association between total adiponectin, HMW adiponectin, HMW-total adiponectin ratio and the severity of coronary atherosclerosis, and to compare their evaluative power for the risk of CAD.

Methods

Serum levels of total and HMW adiponectin were measured in 382 early-onset CAD (EOCAD) patients and 305 matched controls undergoing coronary angiography by enzyme-linked immunosorbent assay (ELISA). Gensini score was used to evaluate the severity of coronary atherosclerosis.

Results

CAD onset age was positively correlated with HMW adiponectin (r = 0.383, P < 0.001) and HMW-total adiponectin ratio (r = 0.429, P < 0.001) in EOCAD patients. Total and HMW adiponectin and HMW-total adiponectin ratio were all inversely correlated with Gensini score (r = −0.417, r = −0.637, r = −0.578, respectively; all P < 0.001). Multivariate binary logistic regression analysis demonstrated that HMW adiponectin and HMW-total adiponectin ratio were both inversely correlated with the risk of CAD (P < 0.05). ROC analysis indicated that areas under the ROC curves of HMW adiponectin and HMW-total adiponectin ratio were larger than that of total adiponectin (P < 0.05).

Conclusions

Adiponectin is cardioprotective against coronary atherosclerosis onset in EOCAD patients. HMW adiponectin and HMW-total adiponectin ratio show stronger negative associations with the severity of coronary atherosclerosis than total adiponectin does. HMW adiponectin and HMW-total adiponectin ratio are effective biomarkers for the risk of CAD in Chinese population.     

The prediction roles of asymmetric dimethyl-arginine,adiponectin and apelin for macroangiopathy in patients with impaired glucose regulation

Purpose

To investigate the effects of asymmetric dimethyl-arginine (ADMA), adiponectin (APN) and apelin in predicting macroangiopathy in impaired glucose regulation (IGR) patients.

Methods

A total of 210 patients undergoing oral glucose tolerance test were included in this study. They were classified to normal glucose tolerance (NGT, n = 42), impaired fasting glucose (IFG, n = 36), impaired glucose tolerance (IGT, n = 92, including 44 IGT1 and 48 IGT2 patients) and IFG + IGT (n = 40) groups. APN, apelin and ADMA levels, blood pressure, blood lipid, insulin, body mass index (BMI), and homeostasis model assessment of insulin resistance (HOMA-IR) were detected. The severity and extent of coronary atherosclerosis were determined by the Gensini score.

Results

The prevalence of coronary heart disease and Gensini scores in IGT and IFG + IGT groups were similar but both were higher than NGT and IFG groups (all P < 0.05). Lower APN, higher ADMA and apelin levels were witnessed in IGT and IGT + IFG groups compared with NGT and IFG groups (all P < 0.05). IGT2 group had higher 2-h PG and apelin levels and Gensini scores but lower APN levels than IGT1 group (all P < 0.05). Gensini score was positively correlated with apelin (r = 0.669) and ADMA (r = 0.764), but were negatively correlated with APN (r = –0.555, all P < 0.001). ADMA and APN were the independent factors affecting Gensini score.

Conclusion

ADMA and APN levels could be predictive factors for macroangiopathy in IGR patients, especially in IGT cases.     

Relationship between retinal arteriolar narrowing and myocardial perfusion: multi-ethnic study of atherosclerosis

Retinal arteriolar narrowing is a marker of chronic hypertension. Myocardial perfusion reflects microvascular processes in the heart. The relationship between these 2 measures has not been studied previously and is examined in 212 men and women aged 45 to 84 years and free of cardiovascular disease diagnoses. Retinal caliber was measured through fundus photography and presented as central retinal arteriolar and venular caliber equivalents. Myocardial blood flow was measured using MRI during rest and adenosine-induced hyperemia. Among subjects with no coronary artery calcification (n=98), smaller retinal arteriolar caliber was associated with lower hyperemic myocardial blood flow and perfusion reserve (calculated as the ratio of hyperemic:resting blood flow). Mean hyperemic blood flow (3.43, 3.28, 3.26, and 3.09 mL/min per gram; P(linear)=0.006) and mean perfusion reserve (3.52, 3.37, 3.19, and 3.10; P(linear)=0.01) progressively decreased across decreasing quartiles of retinal arteriolar caliber. These associations remained significant after adjusting for age, gender, and race/ethnicity but were no longer significant after additionally adjusting for other cardiovascular risk factors. In contrast, among subjects with coronary calcification (n=114), retinal arteriolar caliber was not associated with hyperemic myocardial blood flow (P(linear)=0.73) or perfusion reserve (P(linear)=0.79). There were no associations between retinal venular caliber and perfusion measurements. We conclude that narrower retinal arterioles were associated with lower hyperemic myocardial blood flow and perfusion reserve in asymptomatic adults with no coronary calcification, which is partially mediated by traditional cardiovascular risk factors. This finding suggests that retinal arteriolar narrowing may serve as a marker of coronary microvascular disease.     

Retinal microvascular structure and function in patients with risk factors of atherosclerosis and coronary artery disease

Objective

Retinal microvascular signs are markers of cardiovascular disease risk. There are limited data, on relationships between retinal microvascular signs and retinal microvascular endothelial function. We sought to determine the relationship of retinal vascular signs with retinal microvascular endothelial function in patients with or at high risk of coronary artery disease.

Methods

Participants with atherosclerosis risk factors and coronary disease (n = 258; mean age 57 ± 11 years) were recruited to have static and dynamic retinal vascular assessment. Retinal arteriolar dilatation in response to flicker light (FI–RAD) was measured using the Digital Vessel Analyser and expressed as percentage increase over baseline diameter. Static retinal photographs were acquired utilising a digital fundus camera for measurement of central retinal artery and vein equivalent (CRAE and CRVE), arteriovenous nicking (AVN) and focal arteriolar narrowing (FAN).

Results

Intra-class correlation coefficient was 0.82 for flicker-light induced retinal arteriolar dilatation. There were modest associations in retinal vascular measurements between eyes. For each 10 μm decrease in retinal arteriolar diameter, the absolute increase in FI–RAD was 0.28% (95% CI 0.11, 0.45; p = 0.002) independent of age, gender and atherosclerosis risk factors. AVN and FAN were associated with attenuated FI–RAD (β = −0.67%; 95% CI −1.20, −0.15; p = 0.012) and (β = −0.83%; 95% CI −1.44, −0.23; p = 0.007) respectively after adjustment for age and gender.

Conclusion

Assessment of retinal microvascular endothelial function is reproducible and correlated with retinal microvascular structure and signs, independent of atherosclerosis risk factors. Assessment of retinal vascular structure and function may provide insights into atherosclerotic disease.     

Early pregnancy urinary biomarkers of fatty acid and carbohydrate metabolism in pregnancies complicated by gestational diabetes

Aims

Alterations in organic acid biomarkers from fatty acid and carbohydrate metabolism have been documented in type 2 diabetes patients. However, their association with gestational diabetes mellitus (GDM) is largely unknown.

Methods

Participants were 25 GDM cases and 25 non-GDM controls. Biomarkers of fatty acid (adipate, suberate and ethylmalonate) and carbohydrate (pyruvate, l-lactate and β-hydroxybutyrate) metabolism were measured in maternal urine samples collected in early pregnancy (17 weeks) using liquid chromatography–mass spectrometry methods. Logistic regression were used to calculate odds ratios (OR) and 95% confidence intervals (CI).

Results

GDM cases and controls differed in median urinary concentrations of ethylmalonate (3.0 vs. 2.3 μg/mg creatinine), pyruvate (7.4 vs. 2.1 μg/mg creatinine), and adipate (4.6 vs. 7.3 μg/mg creatinine) (all p-values <0.05). Women in the highest tertile for ethylmalonate or pyruvate concentrations had 11.4-fold (95%CI 1.10–117.48) and 3.27-fold (95%CI 0.72–14.79) increased risk of GDM compared with women in the lowest tertile for ethylmalonate and pyruvate concentrations, respectively. Women in the highest tertile for adipate concentrations, compared with women in the lowest tertile, had an 86% reduction in GDM risk (95%CI 0.02–0.97).

Conclusions

These preliminary findings underscore the importance of altered fatty acid and carbohydrate metabolism in the pathogenesis of GDM.     

The relation between coronary artery disease severity and fragmented QRS complex in patients with left bundle branch block

Background

The diagnosis of coronary artery disease (CAD) in patients with LBBB represents a clinical challenge. The presence of fragmented QRS (fQRS) complex on surface ECG may be related to myocardial ischemia, scarring or fibrosis.

Mean platelet volume and coronary artery disease: a systematic review and meta-analysis

Background

Platelets with high hemostatic activity play an important role in the pathophysiology of coronary artery disease(CAD) and mean platelet volume(MPV) has been proposed as an indicator of platelet reactivity. Thus, MPV may emerge as a potential marker of CAD risk. The aim of this study was to conduct a systematic review and meta-analysis comparing mean difference in MPV between patients with CAD and controls and pooling the odds ratio of CAD in those with high versus low MPV.

Methods

Medline and Scopus databases were searched up to 12 March 2013. All observational studies that considered MPV as a study's factor and measured CAD as an outcome were included. Two reviewers independently selected the studies and extracted the data.

Results

Forty studies were included in this meta-analysis. The MPV was significantly larger in patients with CAD than controls with the unstandardized mean difference of 0.70 fL (95% CI: 0.55, 0.85). The unstandardized mean difference of MPV in patients with acute coronary event and in patients with chronic stable angina was 0.84 fL (95% CI: 0.63, 1.04) and 0.46 fL (95% CI: 0.11, 0.81) respectively. Patients with larger MPV (≥ 7.3 fL) also had a greater odds of having CAD than patients with smaller MPV with a pooled odds ratio of 2.28 (95% CI: 1.46, 3.58).

Conclusion

Larger MPV was associated with CAD. Thus, it might be helpful in risk stratification, or improvement of risk prediction if combining it with other risk factors in risk prediction models.     

The influence of lower-extremity function in elderly individuals’ quality of life (QOL): An analysis of the correlation between SPPB and EQ-5D

Background

If an association between a decline in physical performance and subjective QOL is confirmed, the SPPB could be used as a predictor for declining QOL in older people.

Objective

This study aimed to elucidate the association between the short physical performance battery (SPPB) and QOL (EQ-5D) to determine the utility of the SPPB as a predictor of declining QOL.

Methods

The SPPB and the EQ-5D test were performed with a random sample of participants nested in the Korean Longitudinal Study of Aging (KLoSA) panel. Comparisons of the adjusted mean scores on the EQ-5D index between normal and abnormal SPPB groups were performed. We selected the quartiles of the EQ-5D index variables for the analysis. The association between the EQ-5D index and SPPB abnormality was examined using multinomial logistic regression analysis. Additionally, the associations between gait speed and chair stand time and the EQ-5D index were examined using the same analysis.

Results

Four hundred and twenty-two subjects were included in the analysis. The adjusted means for the EQ-5D index were significantly lower when the SPPB score was abnormal (p = 0.022 for men, p = 0.047 for women). An abnormal SPPB score was significantly associated with the lowest quartile of EQ-5D index score (adjusted OR 3.54 in the lowest quartile for men; adjusted OR 2.50 and 3.37 in the lowest and second quartiles for women). Gait speed was significantly associated with the EQ-5D index for participants of both sexes, but standup time was associated with the EQ-5D index only for men.

Conclusions

An abnormal SPPB score was associated with lower QOL. Thus, the SPPB has the potential to be used as an early predictor of declining QOL in clinical settings and epidemiological studies.     

Inverse association of the endogenous thrombin potential (ETP) with cardiovascular death: The Ludwigshafen Risk and Cardiovascular Health (LURIC) study

Background

Coagulation and prothrombotic potential have genuinely been associated with increased cardiovascular risk. However, not all studies in this regard are conclusive. Some clinical trials have shown an increased frequency of cardiovascular complications in patients receiving direct thrombin inhibitors. Previous data from human subjects after acute cardiovascular events showed an inverse association between the thrombin generation marker F1+2 and cardiovascular endpoints indicating that not the lowest, but a slightly elevated propensity for thrombin generation is associated with a lower risk of cardiovascular events. This observation has been supported by findings in animal models of atherosclerosis. Hence, we evaluated the association between the endogenous thrombin potential (ETP) and cardiovascular death (CVD) and markers of vascular dysfunction in a large prospective study with long-term follow up.

Method

After excluding patients receiving anticoagulants we tested ETP in 2196 participants (median follow-up 10 years) for its ability to predict vascular death (CVD). In addition, the association between ETP and sVCAM-1, sICAM-1, LpPLA₂, hsCRP and SAA was determined.

Results

We observed an inverse association between ETP and CVD with the lowest hazard ratio in the 4th ETP quartile. The nadirs of sICAM-1 or sVCAM-1 were observed in the 3rd, for LpPLA₂ in the 4th ETP quartile. Conversely, hsCRP and SAA were highest in the 4th quartile.

Conclusions

These results demonstrate that not the lowest ETP possible, but slightly higher levels are associated with a reduced risk of CVD and lower markers of endothelial dysfunction, suggesting a more complex role of thrombin in cardiovascular disease.     

Association of cardiac events with coronary artery disease detected by 64-slice or greater coronary CT angiography: A systematic review and meta-analysis

Background

The value of ≥ 64-slice coronary CT angiography (CCTA) to determine odds of cardiac death or non-fatal myocardial infarction (MI) needs further clarification.

Methods

We performed a systematic review and meta-analysis using publications reporting events/severity of coronary artery disease (CAD) in patients with suspected CAD undergoing CCTA. Patients were divided into: no CAD, non-obstructive CAD (maximal stenosis < 50%), and obstructive CAD (≥ 50% stenosis). Odds ratios with 95% confidence intervals were calculated using a fixed or random effects model. Heterogeneity was assessed using the I² index.

Results

We included thirty-two studies comprising 41,960 patients with 363 all-cause deaths (15.0%), 114 cardiac deaths (4.7%), 342 MI (14.2%), 69 unstable angina (2.8%), and 1527 late revascularizations (63.2%) over 1.96 (SD 0.77) years of follow-up. Cardiac death or MI occurred in 0.04% without, 1.29% with non-obstructive, and 6.53% with obstructive CAD. OR for cardiac death or MI was: 14.92 (95% CI, 6.78 to 32.85) for obstructive CAD, 6.41 (95% CI, 2.44 to 16.84) for non-obstructive CAD versus no CAD, and 3.19 (95% CI, 2.29 to 4.45) for non-obstructive versus obstructive CAD and 6.56 (95% CI, 3.07 to 14.02) for no versus any CAD. Similar trends were noted for all-cause mortality and composite major adverse cardiovascular events.

Conclusions

Increasing CAD severity detected by CCTA is associated with cardiac death or MI, all-cause mortality, and composite major adverse cardiovascular events. Absence of CAD is associated with very low odds of major adverse events, but non-obstructive disease significantly increases odds of cardiac adverse events in this follow-up period.     

Education and age affect skill acquisition and retention in lay rescuers after a European Resuscitation Council CPR/AED course

Objectives

To examine whether education and age affect skill acquisition and retention in lay rescuers after a European Resuscitation Council (ERC) CPR/AED course.

Background

Because of the importance of bystander CPR/AED skills in the setting of cardiac arrest, acquisition and retention of resuscitation skills has gained a great amount of interest.

Methods

The ERC CPR/AED course format for written and practical evaluation was used. Eighty lay people were trained and evaluated at the end of the course, as well as at one, three, and six months.

Results

Retention of CPR/AED skills improved over time, recording the lowest practical scores at one month after initial training and the lowest written scores at initial training. In practical evaluation scores, when examined longitudinally, age presented a significant adverse effect and higher background education presented a non-significant positive effect. Moreover, regarding written evaluation scores, when examined longitudinally, education presented a significant positive effect while age did not significantly correlate with written scores.

Conclusions

Education and age affected retention of CPR/AED skills in lay rescuers. Also, our results suggest that the ERC CPR/AED course format may be poorly designed to discriminate between participants with different levels of practical and written resuscitation skills and merit a thorough investigation in future studies.