Treatment with Optimal Dose Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers Has a Positive Effect on Long-Term Survival in Older Individuals (Aged >70 Years) and Octogenarians with Systolic Heart Failure.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is a disease of older people, but the target doses of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are unknown. OBJECTIVE: To evaluate the association of ACEI/ARB dose level with long-term survival in stable older patients (aged >70 years) and octogenarian outpatients with HFrEF. POPULATION AND METHODS: A total of 138 outpatients aged >70 years (35.5 % > 80 years), with an LVEF <40 % and who were clinically stable on optimal therapy were followed up for 3 years. The ACEI/ARB doses were categorized as: none (0), low (1-50 % target dose), and high (50-100 % target dose). The Cox regression survival model was adjusted for age, ischemic etiology, and renal function. RESULTS: ACEIs/ARBs were prescribed to 91.3 % of patients, and 52.9 % received the high dose. Survival improved with increasing ACEI/ARB dose level in the total population (Hazard Ratio [HR] = 0.67; 95 % confidence interval [CI] 0.55-0.82; p < 0.001), older patients aged >70 years (HR = 0.65; 95 % CI 0.51-0.83; p < 0.001), and octogenarians (HR = 0.71; 95 % CI 0.51-0.99; p = 0.045). The low (HR = 0.35; 95 % CI 0.16-0.76; p = 0.008) and high doses (HR = 0.13; 95 % CI 0.06-0.32; p < 0.001) improved survival compared with not receiving ACEIs/ARBs. The high dose was associated with a better survival than the low dose in the total population (HR = 0.35; 95 % CI 0.19-0.67; p = 0.001) and in a propensity score-matched cohort (HR = 0.41; 95 % CI 0.16-1.02; p = 0.056). In octogenarians, all dose levels were associated with improved survival compared with not receiving ACEIs/ARBs, but there was no difference between ACEI/ARB doses. CONCLUSION: The achieved optimal dose of ACEIs/ARBs in ambulatory older people with HFrEF is associated with long-term survival.

The importance of assessing nutritional status in elderly patients with heart failure.

Heart failure (HF) is a syndrome characterized by high morbidity and mortality, despite advances in medical and device therapy that have significantly improved survival. The outcome of HF in elderly patients results from a combination of biological, functional, psychological, and environmental factors, one of which is nutritional status. Malnutrition, as well as HF, is frequently present with aging. Early detection might lead to earlier intervention. It is our goal to review the importance of nutritional status in elderly patients with HF, as well as tools for assessing it. We also propose a simple decision algorithm for the nutritional assessment of elderly patients with HF.

Heart rate reduction with ivabradine in patients with acute decompensated systolic heart failure.

INTRODUCTION: In patients with acute decompensated systolic heart failure (ADSHF) high resting heart rate (HR) could be either a compensatory mechanism or contribute to worsening heart failure. The aim of this study was to evaluate, in patients with ADSHF and resting HR >70 bpm, the early (within 24 h) and late (at discharge) effects of oral administration of ivabradine on HR reduction. METHODS: Ten consecutive patients with ADSHF, left ventricular ejection fraction <40 % and HR >70 bpm, without other acute conditions or inotropic therapy, began open-label treatment with oral ivabradine according to a pre-established Heart Failure Unit protocol. We obtained clinical and laboratory data at four periods: admission (T0), immediately before initiation of ivabradine (T2), 24 h after initiation of ivabradine (T3), and at discharge (T4). RESULTS: Ivabradine was administered in 60 % of the patients before the second day. HR decreased 10.7 ± 7.2 bpm at T3 (p < 0.001) and 16.3 ± 8.2 bpm at T4 (p = 0.002). The systolic blood pressure decreased at T3 (p = 0.012), returning to baseline values at T4. There was no change in diastolic and mean blood pressure. New York Heart Association (NYHA) class improvement by two levels was associated with lower HR at T4 (p = 0.033). HR and N-terminal pro-brain natriuretic peptide (Nt-ProBNP) at baseline correlated significantly [Spearman correlation coefficient (rs) = 0.789, p = 0.013]. Total Nt-ProBNP reduction correlated with the HR before (r = 0.762, p = 0.028) and after (T3: r = 0.647, p = 0.083; T4: r = 0.738, p = 0.037) ivabradine addition. CONCLUSION: In the present cohort of patients with ADSHF and HR >70 bpm, the selective reduction of HR with oral ivabradine was safe and efficient.

Independent association of the variant rs1333049 at the 9p21 locus and coronary heart disease.

INTRODUCTION: Recent genome-wide association studies have identified single-nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). Among them, the SNP rs1333049 has demonstrated a consistent association with CAD, which has been successfully replicated in several populations. AIM: To investigate whether the SNP rs1333049 located on the 9p21 chromosome is an independent risk factor for CAD in a Portuguese population. METHODS: We performed a case-control study which included 1406 individuals, 723 consecutive coronary patients (mean age 53.71 +/- 8.9 years, 79.9% male and 683 controls without coronary disease (mean age 53.3 +/- 10.5 years, 73.9% male). Cases and controls were selected so as not to be significantly different in terms of gender and age. We studied the SNP rs1333049 at the 9p21 locus in all individuals, using standard PCR combined with the TaqMan technique (Applied Biosystems). The allelic and genotype distribution (C/G), odds ratios and corresponding confidence intervals for CAD risk were determined. A forward Wald logistic regression analysis model was constructed, adjusted for age, gender, conventional risk factors, biochemical markers and the genotypes under study, in order to determine which variables were linked significantly and independently with CAD. RESULTS: The C allele was found in 60% of the CAD patients and 53% of the controls, with OR = 1.33; p = 0.0002. The CC genotype appeared in 35.7% of CAD patients, with OR = 1.34, p = 0.010. The heterozygous CG genotype was present in 48.1% of the CAD patients and 47% of the controls, and did not present vascular risk (OR = 1.05, p = 0.670). After logistic regression analysis, the CC genotype remained in the equation with OR = 1.7; p = 0.018 and CG with OR = 1.5, p = 0.048. CONCLUSION: In the present study we replicated the coronary risk linked to the recently discovered variant rs1333049 on the 9p21 chromosome in a Portuguese population. Although the mechanism underlying the risk is still unknown, the robustness of this risk allele in risk stratification for CAD has been consistent, even in very different populations. The presence of the CC or CG genotype may thus prove to be useful for predicting the risk of developing CAD in the Portuguese population.

Interaction of paraoxonase-192 polymorphism with low HDL-cholesterol in coronary artery disease risk.

INTRODUCTION: Coronary artery disease (CAD) is the main cause of mortality in developed countries. Increased lipid peroxidation is associated with accelerated progression of atherosclerosis. Paraoxonase (PON1) is an antioxidant enzyme bound to high-density lipoprotein (HDL), which protects against lipid peroxidation and coronary artery disease. PON1 activity is under genetic control and its molecular basis is a polymorphism in the PON1 gene that shows two common isoforms: the wild Q form (192 Gln) with high ability to protect LDL from lipid peroxidation in vitro, and the mutated R (Arg) form with lower ability. AIM: To explore the interaction of the R allele of the paraoxonase gene and low HDL-cholesterol concentrations in CAD risk. METHODS: The study population consisted of 818 individuals, 298 coronary patients, aged 55.0 +/- 10.3 years, 78.9% male, and 520 age and gender matched healthy controls, aged 53.3 +/- 11.7 years, 72.5% male. Low HDL-cholesterol was defined as < 0.90 mmol/l in men and < 1.11 mmol/l in women. Comparisons of genotypes between cases and controls were performed by a chi-square test. Statistical significance was accepted at p < 0.05. Odds ratios and 95% confidence intervals for the RR genotypes and HDL-deficient subjects were computed using univariate analysis (2 x 2 tables). To determine the interaction between the RR paraoxonase genotype and HDL-deficient subjects, we used 4 x 2 epidemiologic tables and synergy measures: the additive model (Rothman's synergy index, SI) and multiplicative model (Khoury's synergy index, SIM). The relative excess risk due to interaction (RERI) and the attributable proportion (AP) due to interaction (Rothman) were calculated. RESULTS: The PON1 RR192 polymorphism was associated with coronary heart disease (OR = 1.61; p = 0.043) in the whole population. HDL-deficient subjects with the RR192 genotype showed increased risk for CAD (OR = 17.38; p < 0.0001) compared to those with normal HDL and RR192 (OR = 1.39; p = 0.348) and HDL-deficient subjects not carrying the RR genotype (OR = 7.79; p < 0.0001). Synergy measures were SI = 2.3, SIM = 1.6; RERI = 9.2. CONCLUSION: These data suggest the existence of a synergistic effect of the PON1 RR192 genotype (with lower antioxidant ability) and HDL-deficient subjects in risk for development of CAD. The AP due to this interaction was 0.53, meaning that 53% of CAD was explained by this interaction.

Percutaneous aortic valvuloplasty in inoperable symptomatic severe aortic stenosis in the very elderly.

Aortic valve replacement is the first therapeutic option in patients with symptomatic severe aortic stenosis. Given the fact that percutaneous aortic valve implantation is a relatively new procedure and the need for palliative treatment in symptomatic patients with a high surgical risk, percutaneous balloon aortic valvuloplasty is still employed. The authors describe two cases of percutaneous balloon aortic valvuloplasty in very elderly patients with severe calcified aortic stenosis not suitable for cardiac surgery, exacerbated in one case by significant coronary artery disease and left ventricular systolic dysfunction. The authors also review the role of this procedure in current interventional cardiology.

Risk factors and clinical angiographical characteristics of myocardial infarction in women.

INTRODUCTION: Myocardial infarction has a higher incidence in men. However, in women, although less frequent, it has a worse prognosis. OBJECTIVE: With the present work we aim to define the clinical and angiographical characteristics and evolution of myocardial infarction in women compared with men. METHODOLOGY: We studied 235 sequential inpatients with acute myocardial infarction in the Intensive Care Unit who underwent post-infarction catheterization. We then compared female with male patients in terms of risk factors, location and type of infarction, coronary morphology and post-infarction complications. RESULTS: About 22% of the patients hospitalized following myocardial infarction were female. The women were older than the men (65.9 +/- 11.2 vs. 60.3 +/- 11.9; p < 0.01), and had a higher prevalence of high blood pressure (71% vs. 54%, p < 0.05) and a lower prevalence of smoking (19% vs. 50%, p < 0.001). Post-infarction angina was more frequent in women (50% vs. 23%, p < 0.001). Neither Q-wave versus non-Q wave myocardial infarction nor its location were significantly different between the sexes. In terms of coronary morphology, myocardial infarction without significant lesions was more frequent in women (10% vs. 3%, p < 0.05) and there were no significant.