Correlation between the level of evidence and the class of recommendations concerning the pharmacological aspects of the Guidelines of the European Society of Cardiology.

Background The reliability of the recommendations affecting the clinical decisions is being continuously weighed in everyday practice (Gershlick, 2018). The objective of our study was to assess the consistency of the evidence behind the recommendations. Methods We narrowed our focus on the pharmacotherapeutic aspects of the most recent 38 European Society of Cardiology guidelines and analyzed the correlation between the level of evidence (LoE) classified as A, B and C and the class of recommendations (CoR) subdivided into I, IIa, IIb and III. Results Contrary to the majority of recommendations based on a LoE C (43,0%), fewer recommendations were proposed on heavily evidence-supported LoE A (23.8%), which percentage increased with subsequent updates of the guidelines. The most common recommendation was CoR I (44,9%), while the least common recommendation was CoR III (9,2%). While a similar share of A (39,1%) and C (30,1%) LoE shaped the CoR I nearly half (48,8%) of the CoR III were based on LoE C. Conversely, the overwhelming majority of the recommendations within the scope of LoE A were indisputably strong and classified as CoR I (73,7%). Conclusion The pharmacological aspects of the ESC guidelines are predominantly based on LoE C. A greater number of pharmacological recommendations are based on LoE A in comparison to the general ones. Various constraints significantly skew the credibility due to paucity of scientific data. A more nuanced approach is needed, as the guidelines cannot completely substitute the clinical experience and the patient-centered approach in shaping the optimal therapeutic outcome.

Single and joint impact of type 2 diabetes and of congestive heart failure on albuminuria: Data from subgroup analysis and data on moderate albuminuria.

We investigated 180 consecutive patients with congestive heart failure (CHF), of whom 83 had type 2 diabetes (T2DM) and 97 did not have diabetes as well as 223 controls without CHF, of whom 39 had T2DM and 184 did not have diabetes. Data was recorded by standardized interviews and by standardized examination protocols at our institution and were extracted from medical records. Here, we analyzed data on gender differences. Further, we examined the effect of CHF and T2DM on moderate albuminuria, i.e. on an albumin-creatinine ratio (ACR) of 30-300 mg/g. Table 1 shows baseline characteristics of our patients stratified by gender. Table 2 gives ACRs and prevalence rates of albuminuria separately for men and women. In logistic regression analyses adjusting for age, sex, body mass index, LDL cholesterol, history of smoking, history of hypertension, use of statins, ACE inhibitors/angiotensin II receptor blockers, aldosterone antagonists and other antihypertensive medication CHF and T2DM predicted the prevalence of albuminuria in a mutually independent manner in men (OR 4.93 [95% CI 1.76-13.85]; p = 0.002 and OR 2.38 [1.11-5.11]; p = 0.027, respectively), as well as in women (OR 5.66 [95% CI 1.76-18.20]; p = 0.004 and OR 3.53 [1.38-9.08]; p = 0.009, respectively). There was no significant interaction between gender and CHF or T2DM regarding the presence of albuminuria (p = 0.933 and 0.533, respectively), indicating that the association of CHF and T2DM with albuminuria did not differ significantly between men and women. In multivariate analysis of covariance, CHF and T2DM proved to be independent predictors of ACR in women after adjustment for age, sex, body mass index, LDL cholesterol, history of smoking, history of hypertension, use of statins, ACE inhibitors/angiotensin II receptor blockers, aldosterone antagonists and other antihypertensive medication (F = 5.38; p = 0.022 and F = 4.95; p = 0.028, respectively); for men the corresponding F-values were 2.70; p = 0.102 and 3.12; p = 0.079, respectively. There was no significant interaction between gender and CHF or T2DM regarding ACR (p = 0.464 and 0.202, respectively), indicating that the association of CHF and T2DM with the ACR did not differ significantly between men and women. Regarding moderate albuminuria, both CHF and T2DM predicted moderate albuminuria adjusted in a mutually independent manner after the adjustments described above, with ORs of 4.75 [95% CI 2.16-10.45]; p< 0.001 and OR 2.08 [1.13-3.83]; p=0.018, respectively. The data set presented here could be reused with similar patient cohorts for pooled analysis.

The LDL Apolipoprotein B-to-LDL Cholesterol Ratio: Association with Cardiovascular Mortality and a Biomarker of Small, Dense LDLs.

Background and Objective: Small, dense low-density lipoproteins (LDLs) are considered more atherogenic than normal size LDLs. However, the measurement of small, dense LDLs requires sophisticated laboratory methods, such as ultracentrifugation, gradient gel electrophoresis, or nuclear magnetic resonance. We aimed to analyze whether the LDL apolipoprotein B (LDLapoB)-to-LDL cholesterol (LDLC) ratio is associated with cardiovascular mortality and whether this ratio represents a biomarker for small, dense LDLs. Methods: LDLC and LDLapoB were measured (beta-quantification) and calculated (according to Friedewald and Baca, respectively) for 3291 participants of the LURIC Study, with a median (inter-quartile range) follow-up for cardiovascular mortality of 9.9 (8.7−10.7) years. An independent replication cohort included 1660 participants. Associations of the LDLapoB/LDLC ratio with LDL subclass particle concentrations (ultracentrifugation) were tested for 282 participants. Results: In the LURIC Study, the mean (standard deviation) LDLC and LDLapoB concentrations were 117 (34) and 85 (22) mg/dL, respectively; 621 cardiovascular deaths occurred. Elevated LDLapoB/LDLC (calculated and measured) ratios were significantly and independently associated with increased cardiovascular mortality in the entire cohort (fourth vs. first quartile: hazard ratio (95% confidence interval) = 2.07 (1.53−2.79)) and in statin-naïve patients. The association between calculated LDLapoB/LDLC ratio and cardiovascular mortality was replicated in an independent cohort. High LDLapoB/LDLC ratios were associated with higher LDL5 and LDL6 concentrations (both p < 0.001), but not with concentrations of larger LDLs. Conclusions: Elevated measured and calculated LDLapoB/LDLC ratios are associated with increased cardiovascular mortality. Use of LDLapoB/LDLC ratios allows estimation of the atherogenic risk conferred by small, dense LDLs.

The LDL-C/ApoB ratio predicts major cardiovascular events in patients with established atherosclerotic cardiovascular disease.

BACKGROUND AND AIMS: The low density lipoprotein cholesterol to Apolipoprotein B (LDL-C/ApoB) ratio is a validated proxy for low density lipoprotein (LDL) particle size that can be easily calculated from a standard lipid/apolipoprotein profile. Whether it is predictive of cardiovascular events in patients with established atherosclerosis is not known and is addressed in the present investigation. METHODS: We determined the LDL-C/ApoB ratio in a cohort of 1687 subjects with established atherosclerosis. Prospectively, major cardiovascular events (MACE) including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a period of 9.9 ± 4.6 years. The study covers >16,000 patient-years. RESULTS: At baseline, the LDL-C/ApoB ratio was 1.36 ± 0.28 in our cohort. During follow up, a total of 558 first MACE were recorded. The LDL-C/ApoB ratio predicted MACE in univariate Cox proportional hazard analysis (HR 0.90 [0.82-0.98]; p = 0.014); this finding was confirmed after adjustment for age, gender, intensity of statin treatment, hypertension, history of smoking, type 2 diabetes, body mass index and ApoB (HR 0.87 [0.78-0.97]; p = 0.013). CONCLUSIONS: The LDL-C/ApoB ratio is independently predictive of MACE in subjects with established atherosclerosis.

Type 2 diabetes and the risk of cardiovascular events in peripheral artery disease versus coronary artery disease.

INTRODUCTION: The prevalence of type 2 diabetes mellitus (T2DM) is higher in peripheral artery disease (PAD) than in coronary artery disease (CAD) patients, and PAD overall confers higher cardiovascular risk than CAD. How cardiovascular risk compares between PAD and CAD patients when analyses are stratified by the presence of type 2 diabetes is unclear and is addressed in the present study. RESEARCH DESIGN AND METHODS: We prospectively recorded major cardiovascular events (MACE; ie, cardiovascular death, myocardial infarction or stroke) over 10.0±4.7 years in 923 patients with stable CAD, of whom 26.7% had T2DM and in 292 patients with PAD, of whom 42.1% had T2DM. Four groups were analyzed: CAD patients without diabetes (CAD/T2DM-; n=677), CAD patients with T2DM (CAD/T2DM+; n=246), PAD patients without diabetes (PAD/T2DM-; n=169) and PAD patients with T2DM (PAD/T2DM+; n=123). RESULTS: The event rate for MACE increased over our four investigated groups: it was lowest in CAD/T2DM- patients (2.52 events per 100 person-years). It was significantly higher in CAD/T2DM+ patients (3.96 events per 100 person-years; p<0.001), in PAD/T2DM- patients (3.68 events per 100 person-years; p=0.022), and in PAD/T2DM+ patients (7.10 events per 100 person-years; p<0.001), who in turn were at a higher risk than CAD/T2DM+ or PAD/T2DM- patients (p=0.001 and p<0.001, respectively). Cox regression analysis after multivariate adjustment showed that the presence of T2DM (HR=1.44 (95% CI 1.09 to 1.92); p=0.012) and the presence of PAD versus CAD (HR=1.48 (95% CI 1.15 to 1.91); p=0.002) were mutually independent predictors of cardiovascular events. CONCLUSIONS: In conclusion, our data show that T2DM as well as the presence of PAD versus CAD are mutually independent predictors of MACE. Patients with both PAD and T2DM are at an exceedingly high risk of cardiovascular events.

Single and joint impact of type 2 diabetes and of congestive heart failure on albuminuria.

AIMS: Albuminuria is a characteristic feature of diabetic nephropathy, and urine albumin excretion is also increased in patients with congestive heart failure (CHF). However, no data are available on the single and joint associations of type 2 diabetes mellitus (T2DM) and CHF with albuminuria. This issue was addressed in the present study. METHODS: We investigated 4 groups of patients: 180 patients with CHF, of whom 83 had T2DM (CHF+/T2DM+) and 97 did not have diabetes (CHF+/T2DM-) and 223 controls without CHF, of whom 39 had T2DM (CHF-/T2DM+) and 184 did not have diabetes (CHF-/T2DM-). RESULTS: The albumin-creatinine ratio (ACR) was 9.2 [5.7-16.9] mg/g in CHF-/T2DM- patients. Compared to this group it was higher in CHF-/T2DM+ patients (16.1 [7.7-27.8] mg/g; p = 0.004), in CHF+/T2DM- patients (22.0 [9.0-76.8] mg/g; p < 0.001) and in CHF+/T2DM+ patients (66.2 [16.0-177.0] mg/g; p < 0.001), in whom in turn it was higher than in CHF-/T2DM+ (p < 0.001) or in CHF+/T2DM- (p = 0.001) patients. The ACR did not differ significantly between CHF-/T2DM+ and CHF+/T2DM- patients (p = 0.188). In multivariate analysis of covariance, CHF and T2DM proved to be independent predictors of ACR after multivariate adjustment (F = 5.68; p = 0.018 and F = 4.79; p = 0.029, respectively). CONCLUSIONS: We conclude that T2DM and CHF are mutually independent determinants of albuminuria.

Usefulness of Handgrip Strength to Predict Mortality in Patients With Coronary Artery Disease.

Handgrip strength (HGS) is a validated and simple technique to estimate skeletal muscular strength. Whether HGS is a predictor of overall mortality in patients with established coronary artery disease (CAD) is not known, this question is therefore addressed in the present study. We prospectively investigated a cohort of 691 patients with angiographically proven CAD. HGS was measured at baseline, and all-cause death as well as cardiovascular events was recorded over a period of up to 12 years. During a follow-up time of 9.2 ± 3.1 years, 31.3% (n = 216) of the study participants died. Further, 27.8% (n = 192) suffered major cardiovascular events and 56.6% (n = 391) any cardiovascular event. Cox proportional hazard model analysis showed a reduced mortality risk with higher HGS univariately (hazard ratio [HR] for each 5 kg increase in HGS 0.87 [95% confidence interval 0.82 to 0.92]; p <0.001), after adjustment for age and gender (HR 0.86 [0.79 to 0.94]; p = 0.001), and after further adjustment for conventional cardiovascular risk factors (HR 0.86 [0.79 to 0.94]; p = 0.001). Similarly, high HGS was protective of major cardiovascular events as well as of total cardiovascular events (HRs in the fully adjusted model 0.86 [0.78 to 0.94]; p = 0.002 and 0.89 [0.83 to 0.96]; p = 0.002, respectively). From these data, we conclude that HGS is an independent predictor of overall survival and of cardiovascular events in patients with CAD.

Type 2 diabetes mellitus is a strong predictor of LDL cholesterol target achievement in patients with peripheral artery disease.

BACKGROUND AND AIMS: Patients with peripheral artery disease (PAD) are at a very high risk of cardiovascular events and strongly benefit from lowering LDL cholesterol (LDL-C); updated European Society of Cardiology guidelines recommend an LDL-C target of at least <55 mg/dl for these patients. Whether the presence of type 2 diabetes (T2DM) affects LDL-C target achievement in PAD patients is unknown and is addressed in the present study. METHODS: We investigated an unselected consecutive series of 319 patients with sonographically proven PAD, of whom 136 (42.6%) had T2DM. RESULTS: The LDL-C target of <55 mg/dl was met by 8.1% of T2DM patients and by 2.2% of non-diabetic patients (p = 0.014); LDL-C was <70 mg/dl in 22.8% of patients with T2DM and in 9.8% of non-diabetic patients (p = 0.002). Logistic regression analysis showed that the presence of T2DM was an independent and strong predictor of LDL-C target achievement after multivariate adjustment including age, gender, potency adjusted statin use, BMI, smoking, hypertension and other lipid-modifying therapy for the <55 mg/dl target (OR 3.58 [1.08-11.90]; p = 0.038) as well as for the <70 mg/dl target (OR 2.78 [1.40-5.35]; p = 0.003). CONCLUSION: We conclude that T2DM is a strong and independent predictor of LDL-C target achievement among PAD patients; however, also among PAD patients with T2DM only a minority meets the current target of <55 mg/dl and most patients do not even have an LDL-C < 70 mg/dl.

Experience in designing and evaluating a Teleconsultation System supporting shared care of oncological patients.

This poster present our experience in designing, developing and deploying a Web-based Teleconsultation System based on a Patient Centered Oncological Electronic Medical Record (PEMR) specifically de-signed to provide clinicians a cooperative work tool supporting the oncological patient management. An evaluation phase in a clinical setting was performed when the system was deployed in the hospitals. A second evaluation phase after two year of utilization has been carrying on.