The Fen-Phen Finale: A Study of Weight Loss and Valvular Heart Disease

Objective : To assess weight loss, as well as the prevalence of valvular heart disease, in 21 obese women who completed 2 years of treatment by fenfluramine and phentermine (fen-phen) in June 1997. Research Methods and Procedures : Patients were 21 of 22 women who had completed a 1-year, open-label trial of fen-phen combined with lifestyle modification. This study describes the results of a second year of treatment. The presence of valvular heart disease, defined as aortic regurgitation of mild or greater severity and/or mitral regurgitation of moderate or greater severity, was assessed using two-dimensional, color Doppler and pulsed- and continuouswave Doppler examinations. Results : At 2 years, the 21 patients had a mean reduction in initial weight of 13.9 ±10.1%, which was significantly (p<<0.001) smaller than their 1-year loss of 17.1 ±8.7%. Nine of 21 patients reported that they took fen-phen irregularly during the last 4 months of the study because of fears of developing health complications. These nine patients had a 2-year weight loss of 8.7 ± 7.5%, compared with a significantly (p<0.04) larger loss of 17.6 ± 10.5% for participants who reported taking medication regularly. Six of 20 (30%) patients met criteria for valvular heart disease. None of the six had signs or symptoms of this condition. Discussion : Fenfluramine was withdrawn from the market on September 15, 1997 because of concerns that it was associated with valvular heart disease. The present findings are discussed in terms of the potentially favorable long-term benefits of combining lifestyle modification with weight loss medications that are both safe and effective.     

Positive Association between APOA5 rs662799 Polymorphism and Coronary Heart Disease: A Case-Control Study and Meta-Analysis

Objective

Apolipoprotein A5 (APOA5) is associated with plasma triglyceride (TG) levels, a risk factor for coronary heart disease (CHD). This study explored the association between CHD and the APOA5 rs662799 polymorphism.

Methods

We collected 1,521 samples (783 CHD patients and 738 controls) for this case-control study. Meta-analysis was performed using Review Manager Software and Stata Software.

Results

Significant differences were observed between CHD cases and controls at the level of both genotype (χ² = 8.964, df = 2, P = 0.011) and allele (χ² = 9.180, df = 1, P = 0.002, OR = 1.275, 95% CI = 1.089–1.492). A breakdown analysis by gender showed a significant association of APOA5 rs662799 with CHD in males (χ² = 7.770, df = 1, P = 0.005; OR = 1.331, 95% CI = 1.088–1.628). An additional meta-analysis using 21378 cases and 28428 controls established that rs662799 is significantly associated with CHD (P < 0.00001).

Conclusion

Both our case-control study and meta-analysis confirm a significant association between APOA5 rs662799 and CHD. In addition, our results suggest a male-specific association between the APOA5 rs662799 polymorphism and CHD.     

Silent Ischemic Heart Disease and Pericardial Fat Volume in HIV-Infected Patients: A Case-Control Myocardial Perfusion Scintigraphy Study

Objectives

to determine the prevalence of asymptomatic ischemic heart disease (IHD) in HIV patients by myocardial perfusion scintigraphy (MPS) and to determine the value of coronary artery calcium score (CACS), carotid intima-media thickness (cIMT) and pericardial fat volume as screening tools for detection of IHD in subjects with HIV.

Background

Patients with HIV seem prone to early development of IHD.

Methods

105 consecutive HIV patients (mean age 47.4 years; mean duration of HIV 12.3 years; mean CD4+ cell count 636×10⁶/L; all receiving antiretroviral therapy) and 105 controls matched for age, gender and smoking status, without history of IHD were recruited. MPS, CACS, cIMT, pericardial fat volume, and cardiovascular risk scores were measured.

Results

HIV patients demonstrated higher prevalence of perfusion defects than controls (18% vs. 0%; p<0.001) despite similar risk scores. Of HIV patients with perfusion defects, 42% had a CACS = 0. CACS and cIMT were similar in HIV patients and controls. HIV patients on average had 35% increased pericardial fat volume and increased concentration of biomarkers of atherosclerosis in the blood. HIV patients with myocardial perfusion defects had increased pericardial fat volume compared with HIV patients without perfusion defects (314±43 vs. 189±12 mL; p<0.001).

Conclusions

HIV patients had an increased prevalence of silent IHD compared to controls as demonstrated by MPS. The finding was strongly associated with pericardial fat volume, whereas cardiovascular risk scores, cIMT and CACS seem less useful as screening tools for detection of myocardial perfusion defects in HIV patients.     

Multilocus Heterozygosity and Coronary Heart Disease: Nested Case-Control Studies in Men and Women

BackgroundGeneralized allelic heterozygosity has been proposed to improve reproductive fitness and has been associated with higher blood pressure, but its association with chronic disease is not well characterized.MethodsUsing the Affymetrix Genome-Wide Human 6.0 array, we performed whole genome scans in parallel case-control studies of coronary heart disease (CHD) nested in the Health Professionals Follow-up Study and Nurses’ Health Study. We examined ~700,000 single nucleotide polymorphisms (SNPs) in 435 men with incident CHD and 878 matched controls and 435 women with incident CHD with 931 matched controls. We examined the relationship of genome-wide heterozygosity with risk of incident of CHD and with baseline levels of cardiovascular risk factors.ResultsIn both cohorts, approximately 227650 (SD 2000) SNPs were heterozygous. The number of heterozygous SNPs was not related to risk of CHD in either men or women (adjusted odds ratios per 2000 heterozygous SNPs 1.01 [95% confidence interval, 0.91-1.13] in women and 0.94 [0.84-1.06] in men). We also found no consistent associations of genome-wide heterozygosity with levels of lipids, inflammatory markers, adhesion molecules, homocysteine, adiponectin, or body-mass index.ConclusionsIn these parallel nested case-control studies, we found no relationship of multilocus heterozygosity with risk of CHD or its major risk factors. Studies in other populations are needed to rule out associations with lower levels of heterozygosity.     

ABO Blood Groups in Patients with Congenital and Rheumatic Valvular Heart Disease

ABO blood groups were determined in 404 patients who had cardiac surgery for heart disease; 136 of these patients had rheumatic valvular heart disease and 268 had congenital heart disease. The incidence of each ABO blood group was compared to a control series of 2171 patients by means of the ϰ² test. There was no statistical difference in the incidence of ABO blood group when patients with congenital and rheumatic valvular heart disease were compared with the control group.     

Homocysteine and Coronary Heart Disease: Meta-analysis of MTHFR Case-Control Studies, Avoiding Publication Bias

Background

Moderately elevated blood levels of homocysteine are weakly correlated with coronary heart disease (CHD) risk, but causality remains uncertain. When folate levels are low, the TT genotype of the common C677T polymorphism (rs1801133) of the methylene tetrahydrofolate reductase gene (MTHFR) appreciably increases homocysteine levels, so “Mendelian randomization” studies using this variant as an instrumental variable could help test causality.

Methods and Findings

Nineteen unpublished datasets were obtained (total 48,175 CHD cases and 67,961 controls) in which multiple genetic variants had been measured, including MTHFR C677T. These datasets did not include measurements of blood homocysteine, but homocysteine levels would be expected to be about 20% higher with TT than with CC genotype in the populations studied. In meta-analyses of these unpublished datasets, the case-control CHD odds ratio (OR) and 95% CI comparing TT versus CC homozygotes was 1.02 (0.98–1.07; p = 0.28) overall, and 1.01 (0.95–1.07) in unsupplemented low-folate populations. By contrast, in a slightly updated meta-analysis of the 86 published studies (28,617 CHD cases and 41,857 controls), the OR was 1.15 (1.09–1.21), significantly discrepant (p = 0.001) with the OR in the unpublished datasets. Within the meta-analysis of published studies, the OR was 1.12 (1.04–1.21) in the 14 larger studies (those with variance of log OR<0.05; total 13,119 cases) and 1.18 (1.09–1.28) in the 72 smaller ones (total 15,498 cases).

Conclusions

The CI for the overall result from large unpublished datasets shows lifelong moderate homocysteine elevation has little or no effect on CHD. The discrepant overall result from previously published studies reflects publication bias or methodological problems. Please see later in the article for the Editors'' Summary     

Higher Carbohydrate Antigen 125 Levels Are Associated with Increased Risk of Coronary Heart Disease in Elderly Chinese: A Population-Based Case-Control Study

Background

High carbohydrate antigen 125 (CA-125) level was reported to be associated with some cardiac dysfunctions, such as chronic heart failure, but the relationship between CA-125 level and coronary heart disease (CHD) risk remains unclear. The aim of this study was to explore the potential association in a Chinese older population.

Methods

In a population-based case-control study conducted in a Chinese older population, serum CA-125 levels were measured in 1177 diagnosed CHD patients and 3531 age and sex matched control subjects without CHD.

Results

Serum CA-125 level was significantly higher in CHD patients than controls (P < 0.001) with adjustment for age, gender, smoking, drinking, BMI, physical activity, hypertension, dyslipidemia, diabetes mellitus, medication history and family history of CHD and myocardial infarction. CHD risk was doubled (OR: 2.10, 95%CI: 1.69-2.60) among subjects in the highest quartile compared to those in the lowest quartile of CA-125 level (P _trend < 0.001). Furthermore, CA-125 levels were associated with CHD risks in subjects with age over 60 years (OR: 2.19, 95%CI: 1.75-2.73), current smokers (OR: 2.29, 95%CI: 1.50-3.49), current drinkers (OR: 2.35, 95%CI: 1.57-3.53) and subjects with hypertension (OR: 2.04, 95%CI: 1.71-2.43).

Conclusions

Elevated serum CA-125 level might be associated with increased risk of coronary heart disease in the Chinese older population. Further investigations are needed to identify the possible biological role of CA-125 in CHD development in the future.     

同期行冠状动脉旁路移植和心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的临床研究

目的:总结同期行冠状动脉旁路移植(CABG)和心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的临床经验。方法:回顾性分析我院收治的41例接受冠状动脉旁路移植同期行心脏瓣膜置换术的冠心病合并心脏瓣膜病患者的临床资料,对手术方法、主要并发症和术后处理方法进行分析总结。结果:41例患者中,行二次开胸4例(9.76%),应用IABP 2例(4.88%),发生低心排综合征6例(14.63%)、肾功能不全6例(14.63%)、肺功能不全7例(17.07%)、脑合并症1例(2.44%)、胸腔积液4例(9.77%),死亡6例(13.63%),其余患者康复出院。结论:CABG同期行心脏瓣膜置换术治疗冠心病合并心脏瓣膜病的近期疗效满意。术前改善心功能,成熟的手术技术,完全的心肌再血管化,良好的心肌保护,停机困难者尽早应用主动脉内球囊反搏(IABP)及加强术后处理是提高CABG同期行心脏瓣膜置换术疗效的重要措施。     

Prevalence of Valvular Heart Disease in A Cohort of Patients Taking Cabergoline for Management of Hyperprolactinemia

ObjectiveTo determine the prevalence of valvular heart disease in a cohort of patients taking cabergoline for the management of hyperprolactinemia.MethodsA retrospective review of medical records identified patients with hyperprolactinemia who underwent evaluation at Vanderbilt University Medical Center between January and June 2007. The medical records of those patients who were prescribed cabergoline and who underwent elective echocardiography were reviewed for details pertaining to cardiac valvular abnormalities and cabergoline use.ResultsForty-five patients (mean age, 41 ± 10 years [SD]) taking 0.91 ± 0.96 mg of cabergoline per week for a mean duration of 39 ± 29 months underwent echocardiography. Abnormalities of the cardiac valves were present in 3 patients (7%): 1 patient exhibited mild mitral regurgitation, 1 patient had focal aortic valve thickening, and 1 patient demonstrated mitral valve thickening. We found no significant difference in either the cumulative dose of cabergoline (P = .800) or the duration of cabergoline therapy (P = .745) between those patients with and those without these echocardiographic abnormalities.ConclusionWe found echocardiographic valve abnormalities in 3 of 45 patients (7 %) who had been prescribed cabergoline for the management of hyperprolactinemia. This prevalence of valvular heart disease after approximately 3 years of cabergoline treatment is no different from that previously reported in normal populations as determined by echocardiography. (Endocr Pract. 2008;14:672-677)     

Increased Risk of Sudden Cardiac Arrest in Obstructive Pulmonary Disease: A Case-Control Study

Background

We aimed to determine whether (1) patients with obstructive pulmonary disease (OPD) have an increased risk of sudden cardiac arrest (SCA) due to ventricular tachycardia or fibrillation (VT/VF), and (2) the SCA risk is mediated by cardiovascular risk-profile and/or respiratory drug use.

Methods

A community-based case-control study was performed, with 1310 cases of SCA of the ARREST study and 5793 age, sex and SCA-date matched non-SCA controls from the PHARMO database. Only incident SCA cases, age older than 40 years, that resulted from unequivocal cardiac causes with electrocardiographic documentation of VT/VF were included. Conditional logistic regression analysis was used to assess the association between SCA and OPD. Pre-specified subgroup analyses were performed regarding age, sex, cardiovascular risk-profile, disease severity, and current use of respiratory drugs.

Results

A higher risk of SCA was observed in patients with OPD (n = 190 cases [15%], 622 controls [11%]) than in those without OPD (OR adjusted for cardiovascular risk-profile 1.4 [1.2–1.6]). In OPD patients with a high cardiovascular risk-profile (OR 3.5 [2.7–4.4]) a higher risk of SCA was observed than in those with a low cardiovascular risk-profile (OR 1.3 [0.9–1.9]) The observed SCA risk was highest among OPD patients who received short-acting β2-adrenoreceptor agonists (SABA) or anticholinergics (AC) at the time of SCA (SABA OR: 3.9 [1.7–8.8], AC OR: 2.7 [1.5–4.8] compared to those without OPD).

Conclusions

OPD is associated with an increased observed risk of SCA. The most increased risk was observed in patients with a high cardiovascular risk-profile, and in those who received SABA and, possibly, those who received AC at the time of SCA.     

Higher Urinary Bisphenol A Concentration Is Associated with Unexplained Recurrent Miscarriage Risk: Evidence from a Case-Control Study in Eastern China

BackgroundEvidence about the association between Bisphenol A (BPA) and the risk of recurrent miscarriage (RM) in human being is still limited.ObjectiveWe evaluated the association of urinary BPA concentrations with RM in human being.MethodsA hospital-based 1:2 matched case-control study on RM was carried out in Suzhou and Kunshan in Jiangsu Province in China between August 2008 and November 2011. Total urinary BPA concentrations in 264 eligible urine samples (102 RM patients and 162 controls) were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The Wilcoxon test and conditional logistic regression were used to estimate the differences between the groups and odds ratios (OR) with 95% confidence intervals (CI), respectively.ResultsThe median ± IQR (interquartile range) (P₇₅-P₂₅) values of non-creatinine-adjusted total urinary BPA levels in the RM patients and the controls were 1.66±3.69ng/ml and 0.58±1.07ng/ml, respectively (0.98±2.67μg/g Cr (creatinine) and 0.40±0.77μg/g Cr. The adjusted BPA level was significantly higher in the RM patients than in the controls (Wilcoxon test, Z = 4.476, P<0.001). Higher level of urinary BPA was significantly associated with an increased risk of RM (P-trend <0.001). Compared to the groups with urinary BPA levels less than 0.16μg/g Cr, the women with levels of 0.40–0.93μg/g Cr and 0.93μg/g Cr or above had a significantly higher risk of RM (OR = 3.91, 95%CI: 1.23–12.45 and OR = 9.34, 95%CI: 3.06–28.44) that persisted after adjusting for confounding factors. The time from recently RM date to recruitment does not significantly influence the urinary BPA level (P = 0.090).ConclusionExposure to BPA may be associated with RM risk.     

Pre-Illness Isoflavone Consumption and Disease Risk of Ulcerative Colitis: A Multicenter Case-Control Study in Japan

Introduction

Previous studies have suggested that estrogens play a role in the development of ulcerative colitis (UC). Because isoflavones have a similar structure to 17β-estradiol, dietary consumption of isoflavones may have similar influences on the development of UC. We examined the association between pre-illness isoflavone consumption and the risk of UC.

Materials and Methods

We conducted a hospital-based case control study, and compared the dietary habits of 126 newly diagnosed UC cases with those of 170 age- and gender-matched hospital controls. Information on dietary factors was collected using a self-administered diet history questionnaire. To consider potential changes in dietary habits due to disease symptoms, the habits were assessed separately during the previous 1 month and at 1 year before the recruitment.

Results

In the assessment of dietary habits during the previous 1 month, the highest tertile of isoflavone consumption revealed an increased odds ratio (OR) for UC (OR = 2.79; 95% confidence interval (CI), 1.39–5.59; Trend P = 0.004). A significant association was also observed for the dietary assessment at 1 year before, when most UC cases had not yet experienced their first disease symptoms (OR = 2.06; 95% CI, 1.05–4.04; Trend P = 0.04). Associations were more pronounced in females (OR in highest tertile of isoflavone consumption at 1 year before = 4.76; 95% CI, 1.30–17.5; Trend P = 0.02) but were obscured in males (corresponding OR = 1.21; 95% CI, 0.49–3.01; Trend P = 0.63).

Conclusions

Dietary isoflavone consumption may be associated with an increased risk of UC, particularly in females. Prospective cohort studies are warranted to confirm these findings.     

Serum Inflammatory Cytokine Levels Correlate with Hand-Foot-Mouth Disease Severity: A Nested Serial Case-Control Study

Background

Hand-food-mouth disease (HFMD) cases can be fatal. These cases develop rapidly, and it is important to predict the severity of HFMD from mild to fatal and to identify risk factors for mild HFMD. The objective of this study was to correlate the levels of serum inflammatory cytokines with HFMD severity.

Methods

This study was designed as a nested serial case-control study. The data collected included general information, clinical symptoms and signs, laboratory findings and serum cytokine levels.

Results

The levels of IL-4, IL-6, IL-10, TNF-α and IFN-γ in patients with severe HFMD were significantly higher than in mild patients during the 2nd to 5th day after disease onset. The levels of IL-4, IL-6, IL-10 and IFN-γ increased from the 2nd day to the 4th day and later decreased. The levels of TNF-α were high on the first two days and subsequently decreased. The changes of IL-10, TNF-α and IFN-γ in the controls were similar for all cases. The levels of IL-4, IL-6 and IL-17 in the controls were not significantly different with the progression of HFMD.

Conclusions

Our findings indicate that the IL-4, IL-6, IL-10, TNF-α and IFN-γ levels correlate with HFMD severity.     

Association of the COQ2 V393A Variant with Parkinson's Disease: A Case-Control Study and Meta-Analysis

Both Parkinson’s disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases of uncertain etiology, but they show similarities in their pathology and clinical course. The fact that the gene encoding α-synuclein is associated with both diseases also suggests that they share some genetic determinants. Recent studies in Japan associating MSA with a variant in the COQ2 gene led us to question whether variants in the COQ2 gene are associated with PD in Han Chinese in a case-control study. A total of 564 patients with PD were genotyped using the ligase detection rection, together with 484 gender- and age-matched healthy subjects. The M128V and R387X variants of COQ2 were not detected in patients or controls; instead, we detected only the heterozygous V393A variant (CT genotype). The frequency of the CT genotype encoding the V393A mutation was significantly higher in patients PD (4.08%) than in controls (1.86%), corresponding to an odds ratio of 2.24 (95%CI 1.03 to 4.90, p = 0.037). The frequency of the C allele of the V393A variant was significantly higher in patients with PD than in controls (OR 2.22, 95%CI 1.02 to 4.82, p = 0.039), and this was also observed in a meta-analysis of studies from mainland China, Taiwan and Japan. Subgroup analysis of our data showed that the V393A variant was significantly associated with early-onset PD (OR 3.71, 95%CI 1.51 to 9.15, p = 0.002) but not with late-onset disease (OR 1.65, 95%CI 0.69 to 3.95, p = 0.260). Gender was not significantly associated with either genotype or minor allele frequencies. In conclusion, our findings show for the first time that the V393A variant in the COQ2 gene increases risk of PD among the population of east Asia. These results, combined with research on Japanese, lend genetic support to the hypothesis that oxidative stress underlies pathogenesis of both PD and MSA.