Prevalence and pharmacologic management of familial hypercholesterolemia in an unselected contemporary cohort of patients with stable coronary artery disease

INTRODUCTION: Familial hypercholesterolemia (FH) is an inherited disorder characterized by elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) associated with premature cardiovascular disease. METHODS: Using the data from the START (STable Coronary Artery Diseases RegisTry) study, a nationwide, prospective survey on patients with stable coronary artery disease (CAD), we described prevalence and lipid lowering strategies commonly employed in these patients. The study population was divided into "definite/probable FH," defined as a Dutch Lipid Clinic Network (DLCN) score ≥6, "possible FH" with DLCN 3-5, and "unlikely FH" in presence of a DLCN <3. RESULTS: Among the 4030 patients with the DLCN score available, 132 (3.3%) were classified as FH (2.3% with definite/probable and 1.0% with possible FH) and 3898 (96.7%) had unlikely FH. Patients with both definite/probable and possible FH were younger compared to patients not presenting FH. Mean on-treatment LDL-C levels were 107.8 ± 41.5, 84.4 ± 40.9, and 85.8 ± 32.3 (P < 0.0001) and a target of ≤70 mg/dL was reached in 10.9%, 30.0%, and 22.0% (P < 0.0001) of patents with definite/probable, possible FH, and unlikely FH, respectively. Statin therapy was prescribed in 85 (92.4%) patients with definite/probable FH, in 38 (95.0%) with possible FH, and in 3621 (92.9%) with unlikely FH (P = 0.86). The association of statin and ezetimibe, in absence of other lipid-lowering therapy, was more frequently used in patients with definite/probable FH compared to patients without FH (31.5% vs 17.5% vs 9.5%; P < 0.0001). CONCLUSIONS: In this large cohort of consecutive patients with stable CAD, FH was highly prevalent and generally undertreated with lipid lowering therapies

A new integrated approach to cardiac mechanics: reference values for normal left ventricle

The association between left ventricular (LV) myocardial deformation and hemodynamic forces is still mostly unexplored. The normative values and the effects of demographic and technical factors on hemodynamic forces are not known. The authors studied the association between LV myocardial deformation and hemodynamic forces in a large cohort of healthy volunteers. One-hundred seventy-six consecutive subjects (age range, 16\u201382; 51% women), with no cardiovascular risk factors or any relevant diseases, were enrolled. All subjects underwent an echo-Doppler examination. Both 2D global myocardial and endocardial longitudinal strain (GLS), circumferential strain (GCS), and the hemodynamic forces were measured with new software that enabled to calculate all these values and parameters from the three apical views. Higher LV mass index and larger LV volumes were found in males compared to females (85 \ub1 17 vs 74 \ub1 15\ua0g/m2 and 127 \ub1 28 vs 85 \ub1 18\ua0ml, p < 0.0001 respectively) while no differences of the mean values of endocardial and myocardial GLS and of myocardial GCS were found (p = ns) and higher endocardial GCS in women ( 12\ua030.6 \ub1 4.2 vs 12\ua031.8 \ub1 3.7; p = 0.05). LV longitudinal force, LV systolic longitudinal force and LV impulse were higher in men (16.2 \ub1 5.3 vs 13.2 \ub1 3.6; 25.1 \ub1 7.9 vs 19.4 \ub1 5.6 and 20.4 \ub1 7 vs 16.6 \ub1 5.2, p < 0.0001, respectively). A weak but statistically significant decline with age (p < 0.0001) was also found for these force parameters. This new integrated approach could differentiate normality from pathology by providing average deformation values and hemodynamic forces parameters, differentiated by age and gender

LTF and DEFB1 polymorphisms are associated with susceptibility toward chronic periodontitis development

Objectives: Chronic periodontitis is a common pathological condition that affects the supporting tissue of the teeth, leading to progressive alveolar bone destruction and teeth loss. The disease is caused by bacteria and derives from an altered host immune and inflammatory response, also involving different factors such as the oral hygiene, smoking, and genetic background. The innate immune response, the first line of host defense, could also play an important role in the susceptibility to chronic periodontitis. In this study, we evaluated the possible association between periodontal disease and seven genetic variations within DEFB1 and LTF genes, encoding for \u3b2-defensins 1 and lactoferrin (two members of oral innate immune system), in an Italian isolated population. Subjects and Methods: DEFB1 5\u2032UTR g. -52G>A (rs1799946), g. -44C>G (rs1800972), g. -20G>A (rs11362), 3\u2032UTR c*5G>A (rs1047031), c*87A>G (rs1800971), LTF p.Ala29Thr (rs1126477), and p.Lys47Arg (rs1126478) single nucleotide polymor- phisms (SNPs) were analyzed in 155 healthy individuals and 439 chronic periodontitis patients from North-East Italy. Results: Significant associations were found between periodontitis and g. -20G>A (rs11362) and g. -44C>G (rs1800972) SNPs in DEFB1 gene as well as p.Ala29Thr (rs1126477) and p.Lys47Arg (rs1126478) SNPs in LTF gene. Discussion: Our results suggest the involvement of DEFB1 and LTF genetic variations in the susceptibility toward development of periodontitis

CHA2DS2-VASc Score Predicts Adverse Outcome in Patients with Simple Congenital Heart Disease Regardless of Cardiac Rhythm

Adult patients with simple congenital heart disease (sACHD) represent an expanding population vulnerable to atrial arrhythmias (AA). CHA2DS2-VASc score estimates thromboembolic risk in non-valvular atrial fibrillation patients. We investigated the prognostic role of CHA2DS2-VASc score in a non-selected sACHD population regardless of cardiac rhythm. Between November 2009 and June 2018, 427 sACHD patients (377 in sinus rhythm, 50 in AA) were consecutively referred to our ACHD service. Cardiovascular hospitalization and/or all-cause death were considered as composite primary end-point. Patients were divided into group A with CHA2DS2-VASc score = 0 or 1 point, and group B with a score greater than 1 point. Group B included 197 patients (46%) who were older with larger prevalence of cardiovascular risk factors than group A. During a mean follow-up of 70\ua0months (IQR 40\u201393), primary end-point occurred in 94 patients (22%): 72 (37%) in group B and 22 (10%, p < 0.001) in group A. Rate of death for all causes was also significantly higher in the group B than A (22% vs 2%, respectively, p < 0.001). Multivariable Cox regression analysis revealed that CHA2DS2-VASc score was independently related to the primary end-point (HR 1.84 [1.22\u20132.77], p = 0.004) together with retrospective AA, stroke/TIA/peripheral thromboembolism and diabetes. Furthermore, CHA2DS2-VASc score independently predicted primary end-point in the large subgroup of 377 patients with sinus rhythm (HR 2.79 [1.54\u20135.07], p = 0.01). In conclusion, CHA2DS2-VASc score accurately stratifies sACHD patients with different risk for adverse clinical events in the long term regardless of cardiac rhythm

Influence of heart rate, blood pressure, and beta-blocker dose on outcome and the differences in outcome between carvedilol and metoprolol tartrate in patients with chronic heart failure: results from the COMET trial.

AIMS: We studied the influence of heart rate (HR), systolic blood pressure (SBP), and beta-blocker dose on outcome in the 2599 out of 3029 patients in Carvedilol Or Metoprolol European Trial (COMET) who were alive and on study drug at 4 months after randomization (time of first visit on maintenance therapy). METHODS AND RESULTS: By multivariable analysis, baseline HR, baseline SBP, and their change after 4 months were not independently related to subsequent outcome. In a multivariable analysis including clinical variables, HR above and SBP below the median value achieved at 4 months predicted subsequent increased mortality [relative risk (RR) for HR>68 b.p.m. 1.333; 95% confidence intervals (CI) 1.152-1.542; P120 mmHg 0.78; 95% CI 0.671-0.907; P<0.0013]. Achieving target beta-blocker dose was associated with a better outcome (RR 0.779; 95% CI 0.662-0.916; P<0.0025). The superiority of carvedilol as compared to metoprolol tartrate was maintained in a multivariable model (RR 0.767; 95% CI 0.663-0.887; P=0.0004) and there was no interaction with HR, SBP, or beta-blocker dose. CONCLUSION: Beta-blocker dose, HR, and SBP achieved during beta-blocker therapy have independent prognostic value in heart failure. None of these factors influenced the beneficial effects of carvedilol when compared with metoprolol tartrate at the pre-defined target doses used in COMET

BLITZ-HF: a nationwide initiative to evaluate and improve adherence to acute and chronic heart failure guidelines

Aims: To assess adherence to guideline recommendations among a large network of Italian cardiology sites in the management of acute and chronic heart failure (HF) and to evaluate if an ad-hoc educational intervention can improve their performance on several pharmacological and non-pharmacological indicators. Methods and results: BLITZ-HF was a cross-sectional study based on a web-based recording system with pop-up reminders on guideline recommendations used during two 3-month enrolment periods carried out 3 months apart (Phase 1 and 3), interspersed by face-to-face macro-regional benchmark analyses and educational meetings (Phase 2). Overall, 7218 patients with acute and chronic HF were enrolled at 106 cardiology sites. During the enrolment phases, 3920 and 3298 patients were included, respectively, 84% with chronic HF and 16% with acute HF in Phase 1, and 74% with chronic HF and 26% with acute HF in Phase 3. At baseline, adherence to guideline recommendations was already overall high for most indicators. Among acute HF patients, an improvement was obtained in three out of eight indicators, with a significant rise in echocardiographic evaluation. Among chronic HF patients with HF and preserved or mid-range ejection fraction, performance increased in two out of three indicators: creatinine and echocardiographic evaluations. An overall performance improvement was observed in six out of nine indicators in ambulatory HF with reduced ejection fraction patients with a significant increase in angiotensin receptor-neprilysin inhibitor prescription rates. Conclusions: Within a context of an already elevated level of adherence to HF guideline recommendations, a structured multifaceted educational intervention could be useful to improve performance on specific indicators. Extending this approach to other non-cardiology healthcare professionals, who usually manage patients with HF, should be considered

Should beta-blocker therapy be reduced or withdrawn after an episode of decompensated heart failure? Results from COMET.

BACKGROUND: It is unclear whether beta-blocker therapy should be reduced or withdrawn in patients who develop acute decompensated heart failure (HF). We studied the relationship between changes in beta-blocker dose and outcome in patients surviving a HF hospitalisation in COMET. METHODS: Patients hospitalised for HF were subdivided on the basis of the beta-blocker dose administered at the visit following hospitalisation, compared to that administered before. RESULTS: In COMET, 752/3029 patients (25%, 361 carvedilol and 391 metoprolol) had a non-fatal HF hospitalisation while on study treatment. Of these, 61 patients (8%) had beta-blocker treatment withdrawn, 162 (22%) had a dose reduction and 529 (70%) were maintained on the same dose. One-and two-year cumulative mortality rates were 28.7% and 44.6% for patients withdrawn from study medication, 37.4% and 51.4% for those with a reduced dosage (n.s.) and 19.1% and 32.5% for those maintained on the same dose (HR,1.59; 95%CI, 1.28-1.98; p<0.001, compared to the others). The result remained significant in a multivariable model: (HR, 1.30; 95%CI, 1.02-1.66; p=0.0318). No interaction with the beneficial effects of carvedilol, compared to metoprolol, on outcome was observed (p=0.8436). CONCLUSIONS: HF hospitalisations are associated with a high subsequent mortality. The risk of death is higher in patients who discontinue beta-blocker therapy or have their dose reduced. The increase in mortality is only partially explained by the worse prognostic profile of these patients

Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial

BACKGROUND: Beta blockers reduce mortality in patients who have chronic heart failure, systolic dysfunction, and are on background treatment with diuretics and angiotensin-converting enzyme inhibitors. We aimed to compare the effects of carvedilol and metoprolol on clinical outcome. METHODS: In a multicentre, double-blind, and randomised parallel group trial, we assigned 1511 patients with chronic heart failure to treatment with carvedilol (target dose 25 mg twice daily) and 1518 to metoprolol (metoprolol tartrate, target dose 50 mg twice daily). Patients were required to have chronic heart failure (NYHA II-IV), previous admission for a cardiovascular reason, an ejection fraction of less than 0.35, and to have been treated optimally with diuretics and angiotensin-converting enzyme inhibitors unless not tolerated. The primary endpoints were all-cause mortality and the composite endpoint of all-cause mortality or all-cause admission. Analysis was done by intention to treat. FINDINGS: The mean study duration was 58 months (SD 6). The mean ejection fraction was 0.26 (0.07) and the mean age 62 years (11). The all-cause mortality was 34% (512 of 1511) for carvedilol and 40% (600 of 1518) for metoprolol (hazard ratio 0.83 [95% CI 0.74-0.93], p=0.0017). The reduction of all-cause mortality was consistent across predefined subgroups. The composite endpoint of mortality or all-cause admission occurred in 1116 (74%) of 1511 on carvedilol and in 1160 (76%) of 1518 on metoprolol (0.94 [0.86-1.02], p=0.122). Incidence of side-effects and drug withdrawals did not differ by much between the two study groups. INTERPRETATION: Our results suggest that carvedilol extends survival compared with metoprolo