Complex relationship of obesity and obesity paradox in heart failure – higher risk of developing heart failure and better outcomes in established heart failure

Heart failure (HF) and obesity are major public health problems. Studies have shown that obesity may increase the risk of developing new HF but after patients have developed HF, obesity may be associated with improved outcomes. This paradoxical association of obesity with HF remains poorly understood. It is believed that the obesity paradox may in part be due to the inherent limitations of body mass index (BMI) as a measure of obesity. BMI may not appropriately measure important components of body mass like body fat, fat distribution, lean body mass, and body fluid content and may not be ideal for examining the relationship of body composition with health outcomes. Differentiating between body fat and lean body mass may explain some of the paradoxical association between higher BMI and better prognosis in patients with HF. Paradoxical outcomes in HF may also be due to phenotypes of obesity. Future studies need to develop and test metrics that may better measure body composition and may serve as a better tool for the estimation of the true association of obesity and outcomes in HF and determine whether the association may vary by obesity phenotypes.

• KEY MESSAGES

• Obesity predisposes to heart failure in all age groups. But obesity in heart failure is an area of controversy, because of obesity paradox, the apparent protective effect of overweight and mild obesity on mortality after development of heart failure.

• Traditional markers of obesity do not measure different components of body weight like muscle mass, fat, water, and skeletal weight. Body Mass Index in heart failure subjects does not measure accurately body fat or fluid retention. So new markers of obesity like visceral adiposity index, body composition analysis, sarcopenic status assessment may be helpful in the assessment of heart failure outcomes.

• Different phenotypes of obesity may be responsible for the different morbidity, mortality as well as therapeutic outcomes in heart failure.

     

Lipid,blood pressure and kidney update 2013

The year 2013 proved to be very exciting as far as landmark trials and new guidelines in the field of lipid disorders, blood pressure and kidney diseases. Among these are the International Atherosclerosis Society Global Recommendations for the Management of Dyslipidemia, European Society of Cardiology (ESC)/European Society of Hypertension Guidelines for the Management of Arterial Hypertension, American Diabetes Association Clinical Practice Recommendations, the Kidney Disease: Improving Global Outcomes Clinical Practice Guidelines for Managing Dyslipidemias in Chronic Kidney Disease (CKD) Patients, the American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults, the Joint National Committee Expert Panel (JNC 8) Evidence-Based Guideline for the Management of High Blood Pressure in Adults, the American Society of Hypertension/International Society of Hypertension Clinical Practice Guidelines for the Management of Hypertension in the Community, the American College of Physicians Clinical Practice Guideline on Screening, Monitoring, and Treatment of Stage 1–3 CKD and many important trials presented among others during the ESC Annual Congress in Amsterdam and the American Society of Nephrology Annual Meeting—Kidney Week in Atlanta, GA. The paper is an attempt to summarize the most important events and reports in the mentioned areas in the passing year.     

Reliability of gadolinium-enhanced magnetic resonance imaging findings and their correlation with clinical outcome in patients with sciatica

Background contextGadolinium-enhanced magnetic resonance imaging (Gd-MRI) is often performed in the evaluation of patients with persistent sciatica after lumbar disc surgery. However, correlation between enhancement and clinical findings is debated, and limited data are available regarding the reliability of enhancement findings.PurposeTo evaluate the reliability of Gd-MRI findings and their correlation with clinical findings in patients with sciatica.Study designProspective observational evaluation of patients who were enrolled in a randomized trial with 1-year follow-up.Patients samplePatients with 6- to 12-week sciatica, who participated in a multicentre randomized clinical trial comparing an early surgery strategy with prolonged conservative care with surgery if needed. In total 204 patients underwent Gd-MRI at baseline and after 1 year.Outcome measuresPatients were assessed by means of the Roland Disability Questionnaire (RDQ) for sciatica, visual analog scale (VAS) for leg pain, and patient-reported perceived recovery at 1 year. Kappa coefficients were used to assess interobserver reliability.MethodsIn total, 204 patients underwent Gd-MRI at baseline and after 1 year. Magnetic resonance imaging findings were correlated to the outcome measures using the Mann-Whitney U test for continuous data and Fisher exact tests for categorical data.ResultsPoor-to-moderate agreement was observed regarding Gd enhancement of the herniated disc and compressed nerve root (kappa<0.41), which was in contrast with excellent interobserver agreement of the disc level of the herniated disc and compressed nerve root (kappa>0.95). Of the 59 patients with an enhancing herniated disc at 1 year, 86% reported recovery compared with 100% of the 12 patients with nonenhancing herniated discs (p=.34). Of the 12 patients with enhancement of the most affected nerve root at 1 year, 83% reported recovery compared with 85% of the 192 patients with no enhancement (p=.69). Patients with and without enhancing herniated discs or nerve roots at 1 year reported comparable outcomes on RDQ and VAS-leg pain.ConclusionsReliability of Gd-MRI findings was poor-to-moderate and no correlation was observed between enhancement and clinical findings at 1-year follow-up.     

Effect of an educational program on the prevalence of use of antiplatelet drugs, beta blockers, angiotensin-converting enzyme inhibitors, lipid-lowering drugs, and calcium channel blockers prescribed during hospitalization and at hospital discharge in patients with coronary artery disease

BACKGROUND: There is a marked underutilization of antiplatelet drugs, beta blockers, angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), and lipid-lowering drugs, and an overutilization of calcium channel blockers in elderly patients with coronary artery disease (CAD). METHODS: An ongoing educational program is being given by Dr. Wilbert Aronow on the appropriate utilization of cardiovascular drugs in patients with CAD during hospitalization and at hospital discharge. In a prospective study, charts of 200 unselected patients hospitalized for CAD at least 6 months after the onset of the educational program were analyzed by a medical resident to investigate the appropriate utilization of cardiovascular drugs. The 200 patients included 115 men and 85 women, mean age 70 years, with documented CAD. Of the 200 patients, 127 (64%) had the diagnosis of prior CAD. The use of cardiovascular medications in these 127 patients prior to hospitalization served as a control group. RESULTS: After the educational program, aspirin, clopidogrel, or warfarin was given to 93% of patients compared with 67% in the control group; beta blockers were given to 81% of patients compared with 56% in the control group; ACE inhibitors or ARBs were given to 70% of patients compared with 42% in the control group. Lipid-lowering drugs if dyslipidemia were given to 88% of patients compared with 52% in the control group; calcium channel blockers were given to 18% of patients compared with 24% in the control group. CONCLUSIONS: In patients with CAD, the educational program increased the use of antiplatelet drugs by 26%, beta blockers by 25%, ACE inhibitors or ARBs by 28%, and lipid-lowering drugs by 36%, and decreased the use of calcium channel blockers by 6%.     

The effect of iron loading and iron chelation on the innate immune response and subclinical organ injury during human endotoxemia: a randomized trial

In this double-blind randomized placebo-controlled trial involving 30 healthy male volunteers we investigated the acute effects of iron loading (single dose of 1.25 mg/kg iron sucrose) and iron chelation therapy (single dose of 30 mg/kg deferasirox) on iron parameters, oxidative stress, the innate immune response, and subclinical organ injury during experimental human endotoxemia. The administration of iron sucrose induced a profound increase in plasma malondialdehyde 1 h after administration (433±37% of baseline; P<0.0001), but did not potentiate the endotoxemia-induced increase in malondialdehyde, as was seen 3 h after endotoxin administration in the placebo group (P=0.34) and the iron chelation group (P=0.008). Endotoxemia resulted in an initial increase in serum iron levels and transferrin saturation that was accompanied by an increase in labile plasma iron, especially when transferrin saturation reached levels above 90%. Thereafter, serum iron decreased to 51.6±9.7% of baseline at T=8 h in the placebo group versus 84±15% and 60.4±8.9% of baseline at 24 h in the groups treated with iron sucrose and deferasirox, respectively. No significant differences in the endotoxemia-induced cytokine response (TNF-α, IL-6, IL-10 and IL-1RA), subclinical vascular injury and kidney injury were observed between groups. However, vascular reactivity to noradrenalin was impaired in the 6 subjects in whom labile plasma iron was elevated during endotoxemia as opposed to those in whom no labile plasma iron was detected (P=0.029). In conclusion, a single dose of iron sucrose does not affect the innate immune response in a model of experimental human endotoxemia, but may impair vascular reactivity when labile plasma iron is formed. (Clinicaltrials.gov identifier:01349699)     

SOCIETAL BURDEN OF STROKE REHABILITATION: COSTS AND HEALTH OUTCOMES AFTER ADMISSION TO STROKE REHABILITATION

ObjectiveTo estimate societal costs and changes in health-related quality of life in stroke patients, up to one year after start of medical specialist rehabilitation.DesignObservational.PatientsConsecutive patients who received medical specialist rehabilitation in the Stroke Cohort Out-comes of REhabilitation (SCORE) study.MethodsParticipants completed questionnaires on health-related quality of life (EuroQol EQ-5D-3L), absenteeism, out-of-pocket costs and healthcare use at start and end of rehabilitation and 6 and 12 months after start. Clinical characteristics and rehabilitation costs were extracted from the medical and financial records, respectively.ResultsFrom 2014 to 2016 a total of 313 stroke patients completed the study. Mean age was 59 (standard deviation (SD) 12) years, 185 (59%) were male, and 244 (78%) inpatients. Mean costs for inpatient and outpatient rehabilitation were US$70,601 and US$27,473, respectively. For inpatients, utility (an expression of quality of life) increased significantly between baseline and 6 months (EQ-5D-3L 0.66–0.73, p = 0.01; visual analogue scale 0.77–0.82, p < 0.001) and between baseline and 12 months (visual analogue scale 0.77–0.81, p < 0.001).ConclusionOne-year societal costs from after the start of rehabilitation in stroke patients were considerable. Future research should also include costs prior to rehabilitation. For inpatients, health-related quality of life, expressed in terms of utility, improved significantly over time.LAY ABSTRACTThe objective of this study was to estimate societal costs and changes in health-related quality of life in stroke patients, up to one year after the start of rehabilitation. Participants were stroke patients who received inpatient or outpatient rehabilitation. They completed questionnaires on quality of life, absenteeism, out-of-pocket costs and healthcare use at start and end of rehabilitation and 6 and 12 months after the start of rehabilitation. Rehabilitation costs were obtained from the financial records. From 2014 to 2016 a total of 313 patients completed the study. Mean age was 59 years, 185 (59%) were male and 244 (78%) inpatients. Mean costs for inpatient and outpatient rehabilitation were $70,601 and $27,473, respectively. For inpatients, health-related quality of life increased significantly between baseline and 6 months, and between baseline and 12 months. In conclusion, societal costs one year after the start of rehabilitation were considerable and health-related quality of life improved for inpatients.Key words: stroke, rehabilitation, cost analysis, utility, health-related quality of life

The number of people living with stroke in Europe is expected to increase from 1.1 million per year in 2000 to 1.5 million per year in 2025 (1). Stroke survivors may experience severe functional impairments, including impairments in physical functioning (2), cognition (3), and speech/language (4), which, in turn, lead to limitations in activities and participation and to worse quality of life (QoL) (5). Specialist rehabilitation was proven to be effective in improving functional outcomes after stroke (6), such as motor function, balance, walking speed and activities of daily living (7–9). Furthermore, in stroke patients admitted for inpatient rehabilitation, QoL increased significantly between admission and discharge (10).Besides the fact that rehabilitation after stroke is effective, rehabilitation was also found to be the main contributor to the costs of post-stroke care, according to a systematic review published in 2018 including 42 publications (11). Costs of post-stroke care, but not those of acute care, were included. Rehabilitation in different care settings was evaluated, which included primary, secondary and tertiary care, and the costs often applied to part of the patients and were not described in detail. For the delivery of value-based healthcare (VBHC), it is important to consider not only the health effects and patient-reported outcome measures, but to also evaluate the costs of care, since it is important to achieve good patient outcomes per dollar spent (12, 13).The aim of the current study was therefore: (i) to estimate the 1-year societal costs from the start of the rehabilitation in stroke patients treated in a medical specialist rehabilitation facility in The Netherlands; and (ii) to evaluate health changes in terms of utility (an expression of quality of life) over that year.     

Lesions and virus accumulation in inoculated transgenic tobacco plants expressing the coat protein gene of tobacco mosaic virus

The objective of this work was to identify steps in virus infection which were inhibited in transgenic tobacco plants (Nicotiana tabacum cv. Xanthi) that express the coat protein (CP) gene of the U, strain of tobacco mosaic virus (TMV). These plants were shown to be protected against disease development after inoculation with U,-TMV (P. Powell Abel, R. S. Nelson, B. De, N. Hoffman, S. G. Rogers, R. T. Fraley, and R. N. Beachy, 1986, Science 232, 738-743). Experiments were also conducted to allow comparison between the protection observed for the transgenic plants and cross-protection. In addition to protection against U1-TMV, the CP-expressing transgenic plants were protected against symptom development of infection after inoculation with a severe TMV strain, PV230, a strain which is immunologically related to the U1 strain. The numbers of chlorotic lesions produced on inoculated leaves of CID-expressing transgenic Xanthi plants infected with PV230 were 30%-or-less of those on leaves of control plants. Likewise necrotic lesion numbers produced on inoculated leaves of CP-expressing transgenic Xanthi 'nc' plants infected with U1 were 5%-or-less of those on leaves of control plants. Virus accumulation in the inoculated leaves of the CP-expressing Xanthi plants was substantially lower than that in leaves of control plants and thus correlated well with the lesion numbers. These results indicate that the delay in disease development includes prevention of virus accumulation in the inoculated leaves. Furthermore, there was a substantial reduction in accumulation of virus in the first leaf above the inoculated leaves in transgenic plants compared with control plants. Inoculation with viral RNA rather than virus largely overcame the protection, leading to the conclusion that the presence of the CID on virus particles in the challenge inoculum was necessary for maximum protection. As shown by these studies, expression of the TMV-CP coding sequence in transgenic plants mimics several of the characteristics of classical cross-protection previously reported by other researchers. We therefore refer to the protection observed for the transgenic plants as "genetically engineered cross-protection."