Inflammation and stress-related candidate genes,plasma interleukin-6 levels,and longevity in older adults

Interleukin-6 (IL-6) is an inflammatory cytokine that influences the development of inflammatory and aging-related disorders and ultimately longevity. In order to study the influence of variants in genes that regulate inflammatory response on IL-6 levels and longevity, we screened a panel of 477 tag SNPs across 87 candidate genes in >5000 older participants from the population-based Cardiovascular Health Study (CHS). Baseline plasma IL-6 concentration was first confirmed as a strong predictor of all-cause mortality. Functional alleles of the IL6R and PARP1 genes were significantly associated with 15%–20% higher baseline IL-6 concentration per copy among CHS European–American (EA) participants (all p < 10⁻⁴). In a case/control analysis nested within this EA cohort, the minor allele of PARP1 rs1805415 was nominally associated with decreased longevity (p = 0.001), but there was no evidence of association between IL6R genotype and longevity. The PARP1 rs1805415 – longevity association was subsequently replicated in one of two independent case/control studies. In a pooled analysis of all three studies, the “risk” of longevity associated with the minor allele of PARP1 rs1805415 was 0.79 (95%CI 0.62–1.02; p = 0.07). These findings warrant further study of the potential role of PARP1 genotype in inflammatory and aging-related phenotypes.     

Motivational interviewing in inflammatory bowel disease patients: A useful tool for outpatient counselling

Background

Most inflammatory bowel disease patients miss follow-up visits and are non-adherent to therapy due to the lack of an engaging patient–physician relationship. Motivational interviewing is a patient-centred counselling method used to elicit/strengthen motivation towards change. The aim of this study was to assess the role of motivational interviewing in patients affected by inflammatory bowel disease.

Methods

The study included consecutive patients with inflammatory bowel disease presenting for the first consultation (June 2012–February 2013). All consultations were carried out applying the motivational interviewing approach. After each consultation, patients filled out a questionnaire asking demographic data, and their past and current experience.

Results

Overall, 23 males (51.1%) and 22 females (48.9%), mean age 36.1 ± 15.2 years, were enrolled. Before and after experiencing the motivational interviewing approach (mean visit duration 41.5 ± 8.7 min) “overall satisfaction rate”, “physician's communication skills”, and “perceived empathy” were 60% vs 100%, 40% vs 95.6%, and 40% vs 100%, respectively. Satisfaction was lower in patients affected by indeterminate colitis (p = 0.004), and of younger age (p = 0.02).

Conclusion

The motivational interview approach is appreciated by inflammatory bowel disease patients. Despite being time-consuming, the motivational interview appears considerably worthwhile at the first visit and in younger patients. Motivational interviewing can help physicians to deal with their patients, moving from “cure” to “care”.     

Modified clopidogrel loading dose according to platelet reactivity monitoring in patients carrying ABCB1 variant alleles in patients with clopidogrel resistance

Objectives

The aim of the present study was to investigate the impact of a adjusted clopidogrel loading dose (LD) according to platelet reactivity index in carriers of ABCB1 mutant allele undergoing percutaneous coronary intervention (PCI).

Methods

All patients met the inclusion criteria were recruited in the present study. Platelet reactivity was measured using the vasodilator-stimulated phosphoprotein (VASP) index. High treatment platelet reactivity (HTPR) was determined by a cut-off value of > 50%. The genetic polymorphism of ABCB1 was determined by allele-specific polymerase chain reaction (PCR). In patients carrying ABCB1 and HTPR after a first 300-mg LD of clopidogrel, dose adjustment was performed by using up to 3 additional 300-mg LDs to obtain a VASP index < 50%. The rate of major adverse cardiovascular events (MACE) and major or minor bleeding in one month were recorded.

Results

536 patients were included in the present study. One hundred seventy-two patients (32%) carried ABCB1 mutant allele (11 homozygotes [2%] and 161 heterozygotes [30%]). The VASP index in these patients was significantly higher than in homozygotic patients for the wild allele (65.5 ± 13.8% vs. 47.6 ± 21.8%; p < 0.001). Of the 172 ABCB1 mutant allele carriers, 130 were considered to have HTPR. After a second clopidogrel LD, the VASP index was significantly decreased in these patients (66.9 ± 12.8% vs.50.2 ± 18.3%; < 0.001). Finally, dose adjustment according to platelet reactivity monitoring enabled 88% of ABCB1 mutant allele carriers and 91% of wild allele carriers exhibiting HTPR to reach a VASP index < 50%. The rate of MACE and major or minor bleeding in one-month follow-up between the wild allele carriers and the mutant allele carriers didn't differentiate significantly.

Conclusions

Increased and adjusted clopidogrel loading dose according to platelet reactivity monitoring attenuated clopidogrel resistance in carriers of ABCB1 mutant allele.     

Early repolarization is associated with atrial and ventricular tachyarrhythmias in patients with acute ST elevation myocardial infarction undergoing primary percutaneous coronary intervention

Background

Recent studies found that early repolarization (ER) is significantly more common in survivors of aborted sudden cardiac death. We hypothesized that ER might be more common in patients with ST elevation myocardial infarction (STEMI) who have complications of atrial and ventricular arrhythmias.

Methods

This study included 266 patients with acute STEMI undergoing primary percutaneous coronary intervention. Twelve-lead electrocardiograms were analyzed for ER, defined as J-point elevation ≥ 0.1 mV and “notching” and “slurring” of the terminal part of the QRS complex in at least 2 lateral or inferior leads. Acute and late atrial and ventricular arrhythmic events were evaluated.

Results

The ER pattern was observed in 76 patients (28.6%). Atrial arrhythmia [21/76 (27.6%) vs. 22/190 (11.6%), p = 0.001] and ventricular arrhythmia [16/76 (21.1%) vs. 16/190 (8.4%), p = 0.004] were more frequently complicated in patients with ER than those without during hospitalization. ER was a significant independent predictor of developing atrial (HR = 2.682, 95% CI = 1.355–5.310, p = 0.005) and ventricular arrhythmia (HR = 2.936, 95% CI = 1.360–6.335, p = 0.006). Three patients with ER and ventricular fibrillation expired during hospitalization [3.9% (3/76) vs. 0% (0/190), p = 0.023]. However, the presence of ER did not affect the late recurrence of atrial and ventricular arrhythmia.

Conclusions

The ER pattern is commonly observed in patients with STEMI and associated with atrial and ventricular tachyarrhythmia during acute setting.     

Complement factor H 402His variant confers an increased mortality risk in Finnish nonagenarians: The Vitality 90+ study

Ageing is characterized by chronic low-grade inflammation and the expected lifespan may be affected by several immunological and inflammatory mediators. In this study, we investigated whether the functional Tyr402His polymorphism (rs1061170) on complement factor H (CFH) gene, which is a key inflammatory downregulator, modulates the longevity of 491 nonagenarians in the Vitality 90+ study. Logistic regression analysis and Kaplan–Meier method with the log rank test were used to examine the effect of the CFH Tyr402His polymorphism on 4-year mortality. After follow-up, we observed that risk factor-adjusted mortality was significantly higher among the carriers of CFH 402His allele compared to non-carriers (OR 1.78, 95% CI 1.19–2.67, p = 0.005) and that the survival curves of CFH 402His carriers and non-carriers deviated significantly (p = 0.016). We propose that the increased mortality is inflammation-related and mediated by aberrant complement regulation by the CFH 402His variant.     

Association of RAGE (p.Gly82Ser) and MnSOD (p.Val16Ala) polymorphisms with diabetic retinopathy in T2DM patients from north India

Aims

The present study aimed to examine the association of RAGE (p.Gly82Ser) and MnSOD (p.Val16Ala) polymorphisms with diabetic retinopathy (DR) in north Indian T2DM patients.

Methods

In this case-control association study, 758 T2DM patients were recruited. 446 with retinal neovascularization, microneurysms and hemorrhages were considered as cases (DR) and 312 patients with T2DM and no clinical signs of retinopathy (DNR), were recruited as controls. Genotypes for RAGE (p.Gly82Ser) and MnSOD (p.Val16Ala) polymorphisms were generated by direct sequencing of amplified products.

Results

Genotype distribution of p.Gly82Ser (RAGE) and p.Val16Ala (MnSOD) polymorphisms were significantly different between DR and DNR (p < 0.05) whereas distribution of allele frequency did not differ significantly (p > 0.05). A significantly higher frequency of homozygous Ser82 genotype in DR patients was detected compared with DNR (2.4% vs 0.64%) for p.Gly82Ser (RAGE) polymorphism whereas there was a higher frequency of homozygous Ala16 genotype for p.Val16Ala (MnSOD) polymorphism in DR patients compared with DNR (22.6% vs 19.3%). Binary logistic analyses showed an association of homozygous recessive genotype Ser82 with DR (OR: 2.63%, 95% CI: 0.16–15.88, p < 0.033) for p.Gly82Ser (RAGE) polymorphism. However, we did not find a significant association of p.Val16Ala polymorphism in MnSOD with retinopathy.

Conclusions

The findings indicate a statistically significant association of p.Gly82Ser polymorphism in RAGE with DR in T2DM patients.     

Use of covered Cheatham-Platinum stents in congenital heart disease

Background

Controversy remains regarding the use of covered stents in congenital heart disease (CHD). We evaluate the possibilities and safety of covered Cheatham-Platinum (CCP) stents in CHD.

Methods

Single-center retrospective CHD-database study of all CCP stents, 2003–2012. Three study groups: aortic coarctation (CoA), right ventricular outflow tract pre-stenting for percutaneous revalvulation (RVOT), and miscellaneous. Continuous data expressed as median (range).

Results

114 CCP stents in 105 patients, age 16.8 years (4.2–71.2).CoA group: 54 CCP stents in 51 patients: 3/54 for aneurysm exclusion, in 51/54 covering used “prophylactically” because of increased risk for vessel tear. Overall, CCP stenting increased the coarctation diameter from 6 mm (0–15) to 15 mm (10–20) (p < 0.001).RVOT group: 39 CCP stents in 37 patients (34 with RVOT graft, 3 with transannular patch): the graft lumen had shrunken from nominal 21 mm (10–26) to 13 mm (5–22); with the CCP stent the RVOT was redilated to 22 mm (16–26, p < 0.001 vs stenosis).Miscellaneous group: 21 CCP stents in 17 patients: closure of Fontan-circuit fenestration (n = 5), restoration of superior caval vein (n = 2) or pulmonary artery (n = 3) patency, relief of supra-pulmonary stenosis (n = 2), exclusion of aberrant pulmonary arteries (n = 1), cavopulmonary conduit expansion (n = 2), Blalock–Taussig shunt flow reduction (n = 1), and defibrillator lead protection from sharp stents (n = 1). Hybrid procedures performed in 3/17 patients. CCP stent was used as rescue treatment in 2/patients to seal iatrogenic bleeding.

Conclusion

CCP stents can safely be applied in CHD patients. The covering allows adequate sealing of existing or expected tears, thereby increasing the safety margin with more complete dilation.     

Le ressenti des patients vis-à-vis d’une corticothérapie orale prolongée influence l’adhérence déclarée à ce traitement

Background

In patients treated with systemic glucocorticoids (GCs), it is unknown if beliefs about the treatment are associated with level of reported adherence.

Patients and methods

Cross-sectional study conducted in two departments of internal medicine during a six-month period. All patients receiving long-term GCs therapy were asked to fill in a questionnaire regarding their beliefs about (specific scale of the Beliefs about Medicines Questionnaire) and their adherence to (four-item Morisky-Green scale) GCs. Logistic regression analysis was used to assess association between beliefs about GCs and adherence to treatment.

Results

One hundred and eighty one questionnaires were analysed (women: 79%, median age [IQR]: 47 [33–61] years, median duration of treatment: 18 [7–72] months, median daily dosage of prednisone equivalent: 10 [6–20] mg). Among these 181 patients, 83 (46%) reported a “concern” score equal to or higher than the “necessity” score. Nineteen percent of patients reported a low adherence level. In multivariate analysis, these patients were significantly younger (OR: 0.96 [0.93–0.98] per increasing year of age, P = 0.002) and reported more frequently a “concern” score higher than a “necessity” score (OR: 3.08 [1.27–7.46], P = 0.01) as compared to patients reporting a high adherence level.

Conclusion

Informing patients about the “necessity” of GCs and taking into account their “concerns” about adverse events or their fear of becoming dependent on the medication may improve their adherence to treatment.     

Neuronal Differentiation 1 gene Ala45Thr polymorphism and type 2 diabetes mellitus: A meta-analysis of 7,940 subjects

Background and aimsPrevious studies have shown that there was a possible relationship between human Neuronal Differentiation 1 (NEUROD1) gene Ala45Thr polymorphism and type 2 diabetes mellitus (T2DM) susceptibility. Nevertheless, no public opinion has been formed because of the conflicting results in the past studies. In order to illuminate the potential association of human NEUROD1 gene Ala45Thr polymorphism and T2DM, the present meta-analysis was conducted.Methods and resultsIn the current meta-analysis, 7940 subjects from 14 individual studies were included. The fixed or random effects models were used to evaluate the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CIs). The current meta-analysis found a significant association between NEUROD1 gene Ala45Thr polymorphism and T2DM under allelic (OR: 1.21, 95% CI: 1.04–1.41, P = 0.01), dominant (OR: 0.819, 95% CI: 0.734–0.913, P = 3.31 × 10^?4), heterozygous (OR:1.199, 95% CI: 1.068–1.346, P = 0.002), and additive (OR: 1.33, 95% CI: 1.09–1.62, P = 0.004) genetic models.ConclusionsNEUROD1 gene Ala45Thr polymorphism was significantly related to T2DM, especially in the Asian population. More particularly, the Thr45 allele carriers of the NEUROD1 gene may be more susceptible to T2DM.     

Validity of the primary care diagnosis of diabetes in veterans in the southeastern United States

Aims

To determine the validity of diagnosis of diabetes in primary care.

Methods

Patients with initial primary care diagnosis (ICD-9 code 250.xx) were compared to matched controls (without code or diabetes drugs), and patients meeting VA Diabetes Epidemiology Cohort (DEpiC) criteria (any 250.xx twice, or diabetes drug) in “diagnostic accuracy” (whether hyperglycemia preceded diagnosis) and “predictive accuracy” (whether diabetes drug or A1c ≥6.5% followed diagnosis).

Results

Only 1.8% of primary care diagnoses met ADA criteria, while nonstandard non-fasting morning glucose ≥126 mg/dl or A1c ≥6.5% were utilized in 51.5%; broad “diagnostic accuracy” criteria were met in 53% of 2980 primary care vs. 2% of 13,397 control (p < 0.001), and 60% of 2456 DEpiC patients (p < 0.001). “Predictive accuracy” was 88% in primary care diagnosis vs. 12% control (p < 0.001) and 93% DEpiC patients (p = 0.08), but was higher if ADA criteria were met. Delay from hyperglycemia to diagnosis averaged 12.5 months in primary care vs. 20.1 months in DEpiC patients (p < 0.001).

Conclusions

While generally not based on ADA criteria, the primary care diagnosis of diabetes is valid, and identifies patients earlier than detection by DEpiC criteria. Either primary care diagnosis or DEpiC criteria could be used to trigger electronic reminders aimed to facilitate management.     

No reflow : quels facteurs prédictifs ?

Introduction

During the past 20 years, significant progress has been made in the recanalization of ACS with ST elevation. It is now accepted that the reopening of the large coronary vessels in the acute phase of infarction by thrombolysis or angioplasty is necessary but not sufficient, because in 20–50% of cases, the coronary recanalization is an illusion of reperfusion. This phenomenon is called “no reflow”.

Objective

The main objective of our study was to identify predictors of poor perfusion or “no reflow” in the acute phase of myocardial infarction.

Methods

Observational prospective study, in the department of cardiology and internal medicine, university hospital of Blida, over a period of 28 months from 1st September 2010 to 31st January 2013. We identified all patients hospitalized for myocardial infarction in acute phase, who underwent primary angioplasty or thrombolysis with angiographic control during a good TIMI flow. The endpoint was regression of ST segment (regression < 50% ST-segment defined no reflow).

Results

Three hundred and seventy-nine patients were included. The mean age was 56.3 ± 2.1, 87.8% of patients were male. In total, 35.9% hypertensive, 27.1% diabetic type 2, 50.1% and 10.8% dyslipidemia, smoking. One hundred and forty-seven (38.8%) developed a no reflow. Mortality was 3.9%, strongly correlated with no reflow (P = 0.001). Predictors of no reflow after multivariate analysis were: age (OR 98, 0.961–0.996 95%, P = 0.02), heart rate (1.01, 95% CI 0.998–1.02, P = 0.035), the type 2 diabetes (odds ratio 1.87, CI 1.2–3.0, P = 0.08), reaching the core (OR 7, 95% CI 1.2–18.4, P = 0.027), direct stenting (OR 0.48, 95% CI 0.31–0.78, P = 0.003). An interesting subgroup of patients was identified namely the subgroup strategy deferred primary angioplasty with stenting best reperfusion (OR 3.7, 95% CI 1.5–8.8, P = 0.04), a lower rate of reocclusion of culprit artery and a lower rate of stenting with 23/51 (45.1%) versus 136/136 (100%) of immediate stenting group with a P < 0.001.

Conclusion

No reflow is a common phenomenon, strongly correlated with mortality predictors are age, heart rate, diabetes, achieving the core and direct stenting. The distal embolization in primary angioplasty is an important phenomenon, a delayed stenting strategy appears to limit this phenomenon.     

Glucagon-like peptide-1 receptor agonists and pancreatitis: A meta-analysis of randomized clinical trials

Aims

Several randomized trials with metabolic outcomes have reported that glucagon like peptide-1 receptor agonists (GLP-1 RA) could be associated with an increased risk of pancreatitis. The present meta-analysis aimed to examine this hypothesis.

Methods

An extensive Medline, Embase, and Cochrane Database search for “exenatide”, “liraglutide”, “albiglutide”, “taspoglutide”, “dulaglutide”, “lixisenatide”, and “semaglutide” was performed up to March 31st, 2013. Inclusion criteria: (i) randomized trials, (ii) duration ≥12 weeks; (iii) on type 2 diabetes; and (iv) comparison of GLP-1RA with placebo or active drugs. Mantel–Haenszel odds ratio with 95% confidence interval (MH-OR) was calculated for pancreatitis.

Results

80 eligible trials were identified. Of these, 39 had not disclosed their findings or did not report any information on pancreatitis. The remaining 41 trials enrolled 14,972 patients, with a total exposure of 14,333 patient × years (8353 and 5980 patient × years for GLP-1 receptor agonists and comparators, respectively). The overall risk of pancreatitis was not different between GLP-1RA and comparators (MH-OR: 1.01[0.37; 2.76]; p = 0.99).

Conclusions

The present meta-analysis does not suggest any increase in the risk of pancreatitis with the use of GLP-1RA. However, it should be recognized that the number of observed cases of incident pancreatitis is very small and the confidence intervals of risk estimates are wide.     

Clampless off-pump surgery reduces stroke in patients with left main disease

Background

Surgical revascularization is the most appropriate therapy for patients with significant left main coronary-artery disease (LMD). An incidence of perioperative stroke remains an issue when compared to the early outcomes to percutaneous coronary intervention (PCI). This study evaluates the safety and impact of standardized “clampless” OPCAB techniques, composed of either complete in situ grafting or “clampless” device enabled techniques for stroke reduction in patients undergoing surgical revascularization for LMD.

Methods

Between 1999 and 2009, 1031 patients with LMD underwent myocardial-revascularization at our institution. Of these, 507 patients underwent “clampless” OPCAB and 524 patients underwent conventional on-pump CABG (ONCABG). Data-collection was performed prospectively and a propensity-adjusted regression-analysis was applied to balance patient characteristics. LMD was defined as a stenosis > 50% and endpoints were mortality, stroke, a cardiac-composite (including death, stroke and myocardial-infarction); a non-cardiac composite and complete-revascularization.

Results

In OPCAB patients, the cardiac composite (3.0% vs. 7.8%; propensity-adjusted (PA)OR = 0.27; CI95% 0.12–0.65; p = 0.003) as well as the occurrence of stroke (0.4% vs. 2.9%; PAOR = 0.04; CI95% 0.003–0.48; p = 0.012) were significantly lower while the mortality-rate was well comparable between groups (1.8% vs. 2.5%; PAOR = 0.44; CI95% 0.11–1.71; p = 0.24). The non-cardiac composite was also significantly decreased after OPCAB (8.9% vs. 19.7%; PAOR = 0.55; CI95% 0.34–0.89; p = 0.014) and complete revascularization was achieved for similar proportions in both groups (95.1% vs. 93.7%; p = 0.35).

Conclusions

This study shows the superiority of OPCAB for patients with LMD with regards to risk-adjusted outcomes other than mortality. A “clampless OPCAB strategy”, effectively reduces stroke yielding similar early outcomes as PCI.     

Polymorphisms in fatty acid binding protein 5 show association with type 2 diabetes

Genes for the fatty acid binding proteins (FABP) family encode small 14-15 kDa cytosolic proteins and can be regulated during type 2 diabetes mellitus (T2DM) and obesity. This study compared association of single nucleotide polymorphisms (SNPs) in FABP1-5 with T2DM in different ethnic groups. Associations with T2DM of SNPs in these proteins were assessed in African American (AA), non-Hispanic White (NHW), and Hispanic American (HA) individuals. A total of 650 DNA samples were genotyped; control samples were obtained from Coriell's North American Human Variation Panel Repository (NAHVP) of apparently healthy individuals and T2DM cases were taken from the American Diabetes Association GENNID Study. The rs454550 SNP of FABP5 showed a significant association with T2DM in NHW (OR: 9.03, 95% CI: 1.13-71.73, p = 0.014). Our analysis also identified a new FABP5 SNP (nSNP) that showed a significant association with T2DM in NHW (OR: 0.44, 95% CI: 0.19-0.99, p = 0.045) and AA (OR: 0.17, 95% CI: 0.03-0.80, p = 0.016). The Ala54Thr FABP2 polymorphism was significantly associated with T2DM in HA individuals only (OR: 1.85, 95% CI: 1.05-3.27, p = 0.032). All other FABP SNPs did not show association with T2DM. These findings suggest a potential distinct role(s) of SNPs in FABP5 and FABP2 genes in T2DM in different populations.     

Reclassification of diabetes type in pediatric patients initially classified as type 2 diabetes mellitus: 15 years follow-up using routine data from the German/Austrian DPV database

Objective

To examine change of diagnosis in patients from the German/Austrian multicenter DPV (Diabetes Patienten Verlaufsdokumentation) database initially classified as type 2 diabetes.

Methods

Patients aged ≤20 years at onset, diagnosed between 1995 and 2010 were followed for at least 6 months. Chi-square/Wilcoxon tests were performed to compare patient groups according to diabetes type after reclassification.

Results

From 580 study patients, 60 (10.3%) were reclassified, on average 2.4 years after initial diagnosis as follows: 23 (38.3%) as type 1 diabetes; 9 (15%) as maturity onset diabetes of the young (MODY); 20 (33.3%) as “other specific diabetes forms” and 8 (13.3%) as “remission” of type 2 diabetes. Patients reclassified to type 1 were significantly younger (13.5 ± 2.9 versus 14.0 ± 2.6; p = 0.027) and more often β-cell antibody positive at disease onset (80.0% versus 31.2%; p = 0.002), while patients reclassified as MODY had significantly lower BMI-SDS values than 520 patients with confirmed type 2 diabetes (2.5 ± 1.1 versus 0.9 ± 1.1; p < 0.001). The latter were also considerably more obese than patients in “remission” and those reclassified to “other specific diabetes forms”.

Conclusion

About 10% of patients in the DPV database, initially diagnosed as type 2 diabetes, were retrospectively reclassified.     

The FTO genotype as a useful predictor of body weight maintenance: Initial data from a 5-year follow-up study

Objective

We examined associations between the fat-mass and obesity-associated (FTO) gene (rs9939609) and any weight change over a 5-year period following a 14-week lifestyle intervention among middle-aged Japanese women.

Materials/Methods

One hundred twenty-eight Japanese women (BMI > 25 kg/m²) participated in a 14-week weight loss intervention between 2004 and 2006. Of the participants, 62 consented to the 5-year follow-up measurement session. Of these women, 47 women who achieved a weight loss of at least 10% from their baseline values during the 14-week intervention were included in the analysis. Body weight, body fat, abdominal fat assessed by CT scans, and metabolic risk factors (i.e., blood pressure, lipids, and glucose) were measured at baseline, post-intervention, and at the 5-year follow-up.

Results

During the 5-year non-intervention period, increases in body weight, fat mass, total abdominal fat, and subcutaneous abdominal fat were significantly greater in subjects with the homozygous minor allele (AA genotype, n = 4; 8.5%) than in those with the homozygous major allele (TT genotype, n = 31; 66.0%) or heterozygous allele (TA genotype, n = 12; 25.5%). In multiple regression analyses, the variation in rs9939609 was a significant and independent predictor (P < 0.001) for regaining weight during the 5-year follow-up.

Conclusions

Our data suggest that Japanese women with the risk allele (AA) of rs9939609 may have more difficulty preventing fat gain from reoccurring after weight loss intervention than women with the other genotypes.     

Cardiac resynchronization therapy and AV optimization increase myocardial oxygen consumption,but increase cardiac function more than proportionally

Background

The mechanoenergetic effects of atrioventricular delay optimization during biventricular pacing (“cardiac resynchronization therapy”, CRT) are unknown.

Methods

Eleven patients with heart failure and left bundle branch block (LBBB) underwent invasive measurements of left ventricular (LV) developed pressure, aortic flow velocity-time-integral (VTI) and myocardial oxygen consumption (MVO₂) at 4 pacing states: biventricular pacing (with VV 0 ms) at AVD 40 ms (AV-40), AVD 120 ms (AV-120, a common nominal AV delay), at their pre-identified individualised haemodynamic optimum (AV-Opt); and intrinsic conduction (LBBB).

Results

AV-120, relative to LBBB, increased LV developed pressure by a mean of 11(SEM 2)%, p = 0.001, and aortic VTI by 11(SEM 3)%, p = 0.002, but also increased MVO2 by 11(SEM 5)%, p = 0.04.AV-Opt further increased LV developed pressure by a mean of 2(SEM 1)%, p = 0.035 and aortic VTI by 4(SEM 1)%, p = 0.017. MVO2 trended further up by 7(SEM 5)%, p = 0.22.Mechanoenergetics at AV-40 were no different from LBBB.The 4 states lay on a straight line for Δexternal work (ΔLV developed pressure × Δaortic VTI) against ΔMVO2, with slope 1.80, significantly > 1 (p = 0.02).

Conclusions

Biventricular pacing and atrioventricular delay optimization increased external cardiac work done but also myocardial oxygen consumption. Nevertheless, the increase in cardiac work was ~ 80% greater than the increase in oxygen consumption, signifying an improvement in cardiac mechanoenergetics. Finally, the incremental effect of optimization on external work was approximately one-third beyond that of nominal AV pacing, along the same favourable efficiency trajectory, suggesting that AV delay dominates the biventricular pacing effect — which may therefore not be mainly “resynchronization”.     

The role of FABP2 gene polymorphism in alcoholic cirrhosis

Hypertriglyceridemia and dietary lipids have been suggested to modulate the severity of alcoholic liver disease and the progression to alcoholic cirrhosis (AC). The intestinal fatty acid binding protein (IFABP) is the main transporter of dietary fatty acids into the enterocyte and has a genetic polymorphism, FABP2 A54T that has been associated with hypertriglyceridemia. We determined the frequency of the FABP2 gene polymorphism using PCR-RFLP and measured serum triglycerides, HDL, LDL, total lipids and cholesterol in 67 patients with AC and in 124 unrelated healthy individuals. Frequencies of genotypes and alleles were similar between the two groups. The healthy subjects, who were homozygous for the Thr54 genotype had significantly higher mean triglyceride serum concentrations than those homozygous for the Ala54 genotype (P < 0.05). However, AC patients who were homozygous for the Thr54 genotype, had lower mean triglyceride serum concentrations (P < 0.01), and had a significantly longer period of continued alcohol abuse prior to the diagnosis of liver cirrhosis compared to the AC patients homozygous for the Ala54 genotype (P < 0.05).Our data suggests that the polymorphism Thr54 of the FABP2 gene is associated with a later onset of AC in the lower economic status Mexican population studied.     

Redefining the ECG in urban South Africans: Electrocardiographic findings in heart disease-free Africans

Background

The 12-lead electrocardiogram (ECG) represents an important diagnostic tool for detecting heart disease, but the “normal” ECG in those of African descent has yet to be definitively described.

Methods

We systematically analysed 12-lead ECGs from 387 urban South Africans determined to be heart disease free (using the Minnesota code) following advanced cardiologic assessment, including echocardiography, at the Baragwanath Hospital in Soweto, South Africa.

Results

123 males (32%, 41.2 ± 14.5 years) and 264 females (37.4 ± 14.2 years) were studied. Most were in sinus rhythm (87%) and had normal axis (89%). Mean interval data were: PR interval (156 ± 28 ms; 95% CI: 153–159 ms), QRS duration (82 ± 16 ms; 95% CI: 80–84 ms), QT interval (379 ± 48 ms; 95% CI: 374–384 ms) and QTc interval (426 ± 32 ms; 95% CI: 423–429 ms). Overall, 199 (51%; 95% CI: 46.0% to 56.0%) subjects had an ECG “abnormality” or normal variant and 67 ECGs (17%; 95% CI: 13.3% to 20.7%) had major and minor abnormalities. ECG changes normally ascribed to myocardial ischaemia were: i) ST elevation (9.3%; 95% CI: 6.2 to 11.9%), ii) Q waves (7.4%; 95% CI: 4.4 to 9.5%) and iii) ST depression (2.3%; 95% CI: 0.8 to 3.8%). Sokolow–Lyon Index voltage exceeding 38 mm indicative of left ventricular hypertrophy was more prominent in males than females (23.6% vs. 6.4%; OR = 4.5; 95% CI: 2.3–8.5).

Conclusions

These data provide a contemporary reference to the 12-lead ECG in urban South Africans found to be heart disease free, with both major and minor abnormalities detected.