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1.  Non-cardiovascular comorbidity, severity and prognosis in non-selected heart failure populations: A systematic review and meta-analysis☆ 
Non-cardiovascular comorbidities are recognised as independent prognostic factors in selected heart failure (HF) populations, but the evidence on non-selected HF and how comorbid disease severity and change impacts on outcomes has not been synthesised. We identified primary HF comorbidity follow-up studies to compare the impact of non-cardiovascular comorbidity, severity and change on the outcomes of quality of life, all-cause hospital admissions and all-cause mortality.
Literature databases (Jan 1990–May 2013) were screened using validated strategies and quality appraisal (QUIPS tool). Adjusted hazard ratios for the main HF outcomes were combined using random effects meta-analysis and inclusion of comorbidity in prognostic models was described.
There were 68 primary HF studies covering nine non-cardiovascular comorbidities. Most were on diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD) and renal dysfunction (RD) for the outcome of mortality (93%) and hospital admissions (16%), median follow-up of 4 years. The adjusted associations between HF comorbidity and mortality were DM (HR 1.34; 95% CI 1.2, 1.5), COPD (1.39; 1.2, 1.6) and RD (1.52; 1.3, 1.7). Comorbidity severity increased mortality from moderate to severe disease by an estimated 78%, 42% and 80% respectively. The risk of hospital admissions increased up to 50% for each disease. Few studies or prognostic models included comorbidity change.
Non-cardiovascular comorbidity and severity significantly increases the prognostic risk of poor outcomes in non-selected HF populations but there is a major gap in investigating change in comorbid status over time. The evidence supports a step-change for the inclusion of comorbidity severity in new HF interventions to improve prognostic outcomes.
•We synthesise the prognosis evidence on non-CVD comorbidity and severity in non-selected HF•Most studies focused on three comorbid diseases for mortality and admissions and none for QoL•COPD, diabetes and CKD increased mortality and admission risk in non-selected HF•Severity studies were few but where available, risk increased with disease severity•Comorbidity severity is important but has yet to be included in HF prognostic models
PMCID: PMC4518480  PMID: 26080284
Heart failure; Comorbidity; Prognosis; Systematic review; Meta-analysis
2.  Intravenous (−)-epicatechin reduces myocardial ischemic injury by protecting mitochondrial function 
International journal of cardiology  2014;175(2):297-306.
Targeting the mitochondria during ischemia/reperfusion (IR) can confer cardioprotection leading to improved clinical outcomes. The cardioprotective potential of (−)-epicatechin (EPI) during IR via modulation of mitochondrial function was evaluated.
Methods and Results
Ischemia was induced in rats via a 45 min occlusion of the left anterior descending coronary artery followed by 1 h, 48 h, or 3 weeks (wk) reperfusion. EPI (10 mg/kg) was administered IV 15 min prior to reperfusion for the single dose group and again 12 h later for the double dose group. Controls received water. Experiments also utilized cultured neonatal rat ventricular myocytes (NRVM) and myoblasts. A single dose of EPI reduced infarct size by 27% at 48 hours and 28% at 3 week. Double dose treatment further decreased infarct size by 80% at 48 h, and 52% by 3 weeks. The protective effect of EPI on mitochondrial function was evident after 1 hr of reperfusion when mitochondria demonstrated less respiratory inhibition, lower mitochondrial Ca2+ load, and a preserved pool of NADH that correlated with higher tissue ATP levels. Mechanistic studies in NRVM revealed that EPI acutely stimulated maximal rates of respiration, an effect that was blocked by inhibitors of the mitochondrial pyruvate carrier, nitric oxide synthase, or soluble guanylyl cyclase. In myoblasts, knockdown of components of the mitochondrial pyruvate carrier blocked EPI-induced respiratory stimulation.
IV EPI confers cardioprotection via preservation of mitochondrial function potentially through enhanced substrate provision. These provocative results document a novel mechanism of a natural product with potential clinical utility.
PMCID: PMC4506135  PMID: 24908200
myocardial ischemia-reperfusion injury; epicatechin; cardiac metabolism; mitochondrial Ca2+; mitochondrial pyruvate carrier
3.  Patient Characteristics and Comorbidities Associated With Cerebrovascular Accident following Acute Myocardial Infarction in the United States 
International journal of cardiology  2014;175(2):323-327.
Although cerebrovascular accident (CVA) is a relatively infrequent complication of acute myocardial infarction (AMI), the occurrence of CVA in patients with AMI is associated with increased morbidity and mortality. We wanted to assess post-AMI CVA rate in the United States and identify associated patient characteristics, comorbidities, type of AMI, and utilization of invasive procedures.
This is an observational study from the Nationwide Inpatient Sample, 2006–2008. Using multivariate regression models, we assessed predictive risk factors for post-AMI CVA among patients admitted for AMI.
Among the 1,924,413 patients admitted for AMI, the overall rate of CVA was 2% (Ischemic stroke: 1.47%, transient ischemic attack [TIA]: 0.35% and hemorrhagic stroke: 0.21%). In this sample of AMI patient, higher incidence of CVA was associated with: CHF (Adjusted odds ratio [AOR] 1.71; 95% confidence interval [CI], 1.58–1.84,), age over 65 AOR, 1.65; 95% CI, 1.60–1.70, alcohol abuse AOR, 1.60; 95% CI, 1.49–1.73, cocaine use AOR, 1.48; 95% CI, 1.29–1.70, atrial fibrillation AOR, 1.43; 95% CI, 1.39–1.46, Black race AOR, 1.35; 95% CI, 1.30–1.40, female gender AOR, 1.32; 95% CI, 1.29–1.35, peripheral vascular disease [PVD] AOR, 1.26; 95% CI, 1.22–1.30, coronary artery bypass graft (CABG) AOR, 1.22; 95% CI, 1.17–1.27, P <0.0001, STEMI AOR, 1.17; 95% CI, 1.14–1.20 and teaching hospitals AOR, 1.09; 95% CI, 1.06–1.12.
Female gender, older age (age ≥ 65), black ethnicity, comorbidities including CHF, PVD, atrial fibrillation as well as STEMI and undergoing CABG were associated with the highest risk of CVA post- AMI.
PMCID: PMC4121439  PMID: 24874908
Cerebrovascular Accident; Transient Ischemic Attack; Stroke; Acute Myocardial Infarction
International journal of cardiology  2014;176(3):1249-1251.
PMCID: PMC4513354  PMID: 25129277
rs5068; genetic variant; atrial natriuretic peptide; B-type natriuretic peptide; natriuretic peptides; heart failure
6.  Trends in incidence of hypertension in Chinese adults, 1991–2009: the China Health and Nutrition Survey 
Previous studies have shown an upward trend in the prevalence of hypertension, but data on trend of incidence of hypertension are lacking. We seek to investigate the trends in incidence of hypertension and control of incident hypertension among Chinese adults during 1991–1997 and 2004–2009.
Within the China Health and Nutrition Survey (1991–2009), we identified five cohorts of adults (age ≥18 years) who were free of hypertension at baseline of each cohort: cohorts 1991–1997 (n=4107), 1993–2000 (n=4068), 1997–2004 (n=4141), 2000–2006 (n=4695), and 2004–2009 (n=4523). Data on demographics, smoking, alcohol intake, physical activity, body mass index (BMI), and blood pressure were collected through interviews and clinical examination. Hypertension was defined as blood pressure ≥140/90 mmHg or currently using antihypertensive drugs. Multiple generalized estimation equations and Cox regression models were used to test the trends in blood pressure, incidence of hypertension, use of antihypertensive drugs, and control status of incident hypertension.
After controlling for potential confounders, incidence of hypertension (per 100 person-years) significantly increased from 2.9 in 1991–1997 to 5.3 in 2004–2009 (ptrend=0.024); the linear trend was statistically or marginally significant in the age group of 18–39 years, in women, in rural residents, and in adults with normal BMI. The overall rates of antihypertensive treatment and control of incident hypertension increased significantly from 5.7% and 1.7% in 1991–1997 to 19.9% and 7.6% in 2004–2009, respectively (ptrend<0.001).
The incidence of hypertension has increased in Chinese adults since early 1990s. The treatment and control status of incident hypertension, while improved, remain very poor.
PMCID: PMC4105139  PMID: 24833472
Trends; Incidence; Hypertension; Adults; China
7.  The temporal and spatial expression pattern of ABCG2 in the developing human heart 
International journal of cardiology  2010;156(2):133-138.
The discovery that the adult heart is not a terminally differentiated organ and contains stem/progenitor cells has important implications for the development of cellular therapeutics to treat heart disease. Moreover the discovery of cardiac stem cells might be important in furthering our understanding of both normal and abnormal cardiac development and yet little is known about these cell populations in the developing human heart, which we have focused on in this study.
The presence of ABCG2 and islet-1 expressing cells in human heart was determined using immunohistochemistry and RT-PCR (and western blotting for ABCG2). Cardiac SP cells were isolated using FACS. Co-localisation immunohistochemistry was used to determine if ABCG2 positive cells expressed other known stem/progenitor cell, endothelial markers or cardiac markers.
We observed that ABCG2 expressing cells show a difference in both their temporal and spatial pattern of expression from Islet-1 expressing cardiac progenitors. We identified rare cells that expressed both ABCG2 and markers of other cell lineages including CD31, CD34 and alpha actinin. We also noted the presence of cells that only expressed ABCG2. We isolated cardiac SP cells and confirmed the SP cell phenotype.
Our results suggest that the developing human heart contains at least two distinct cardiac stem/progenitor cell populations one of which, the ABCG2 positive cells, can be readily isolated, suggesting that this tissue could be a useful source of cardiac stem cells.
PMCID: PMC4490625  PMID: 21111494
ABCG2; islet-1; side population cells; embryonic; fetal; human heart
8.  Polymeric stent materials dysregulate macrophage and endothelial cell functions: implications for coronary artery stent 
International journal of cardiology  2014;174(3):688-695.
Biodegradable polymers have been applied as bulk or coating materials for coronary artery stents. The degradation of polymers, however, could induce endothelial dysfunction and aggravate neointimal formation. Here we use polymeric microparticles to simulate and demonstrate the effects of degraded stent materials on phagocytic activity, cell death and dysfunction of macrophages and endothelial cells.
Microparticles made of low molecular weight polyesters were incubated with human macrophages and coronary artery endothelial cells (ECs). Microparticle-induced phagocytosis, cytotoxicity, apoptosis, cytokine release and surface marker expression were determined by immunostaining or ELISA. Elastase expression was analyzed by ELISA and the elastase-mediated polymer degradation was assessed by mass spectrometry.
We demonstrated poly(D,L-lactic acid) (PLLA) and polycaprolactone (PCL) microparticles induced cytotoxicity in macrophages and ECs, partially through cell apoptosis. The particle treatment alleviated EC phagocytosis, as opposed to macrophages, but enhanced the expression of vascular cell adhesion molecule-1 (VCAM) along with decreased nitric oxide production, indicating ECs were activated and lost their capacity to maintain homeostasis. The activation of both cell types induced release of elastase or elastase-like protease, which further accelerated polymer degradation.
This study revealed that low molecule weight PLLA and PCL microparticles increased cytotoxicity and dysregulated endothelial cell function, which in turn enhanced elastase release and polymer degradation. These indicate polymer or polymer-coated stents impose a risk of endothelial dysfunction after deployment which can potentially lead to delayed endothelialization, neointimal hyperplasia and late thrombosis.
PMCID: PMC4070878  PMID: 24820736
poly(L-lactic acid); PLLA; polycaprolactone; PCL; stent; coronary; polymer degradation; macrophage; endothelial cell; dysfunction; elastase
9.  Prediction of heart rate variability on cardiac sudden death in heart failure patients: A systematic review 
International journal of cardiology  2014;174(3):857-860.
PMCID: PMC4318838  PMID: 24804906
Prediction; Heart rate variability; Cardiac sudden death; Heart failure patients; Systematic review
International journal of cardiology  2014;174(2):368-375.
To better understand the hemodynamic and autonomic reflex abnormalities in heart-failure patients (HF), we investigated the influence of group III/IV muscle afferents on their cardiovascular response to rhythmic exercise.
Nine HF-patients (NYHA class-II, mean left ventricular ejection-fraction: 27±3%) performed single leg knee-extensor exercise (25/50/80% peak-workload) under control conditions and with lumbar intrathecal fentanyl impairing μ-opioid receptor-sensitive muscle afferents.
Cardiac-output (Q) and femoral blood-flow (QL) were determined, and arterial/venous blood samples collected at each workload. Exercise-induced fatigue was estimated via pre/post-exercise changes in quadriceps strength. There were no hemodynamic differences between conditions at rest. During exercise, Q was 8–13% lower with Fentanyl-blockade, secondary to significant reductions in stroke volume and heart rate. Lower norepinephrine spillover during exercise with Fentanyl revealed an attenuated sympathetic outflow that likely contributed to the 25% increase in leg vascular conductance (p<0.05). Despite a concomitant 4% reduction in blood pressure, QL was 10–14% higher and end-exercise fatigue attenuated by 30% with Fentanyl-blockade (p<0.05).
Although group III/IV muscle afferents play a critical role for central hemodynamics in HF-patients, it also appears that these sensory neurons cause excessive sympatho-excitation impairing QL which likely contributes to the exercise intolerance in this population.
PMCID: PMC4075285  PMID: 24794967
circulation; exercise pressor reflex; sensory neurons; autonomic control
12.  A link between ATP and SUR2A: A novel mechanism explaining cardioprotection at high altitude☆ 
PMCID: PMC4461008  PMID: 25885875
SUR2A; Hypoxia; High Altitude; Cardioprotection
13.  Relationship of Change in Traditional Cardiometabolic Risk Factors to Change in Coronary Artery Calcification Among Individuals with Detectable Subclinical Atherosclerosis: The Multi-Ethnic Study of Atherosclerosis 
Data describing relationships between change in risk factors and coronary artery calcification (CAC) are lacking and could inform optimal cardiovascular disease prevention and treatment strategies. This study aimed to examine how change in traditional cardiometabolic risk factors related to change in CAC among individuals with detectable subclinical atherosclerosis.
Latent growth modeling was used to examine change in cardiometabolic risk factors (waist circumference, body mass index, systolic and diastolic blood pressure, high- and low-density lipoprotein cholesterol, triglycerides, and glucose) related to change in CAC up to an average 4.9-year follow-up in a multi-ethnic cohort of 3,398 asymptomatic individuals (57.8% men) who had detectable CAC (score > 0) at baseline, adjusting for baseline risk factor levels and CAC values, age, gender, race/ethnicity, smoking, family history of CVD, income, and use of antihypertensive, lipid-lowering, and glucose-lowering medications.
Greater declines in blood pressure (systolic and diastolic) and low-density lipoprotein cholesterol at follow-up were each associated with greater CAC progression. The observed inverse associations were attributable to greater CAC progression in participants taking antihypertensive and lipid-lowering drugs who, as expected, had declines in blood pressure and lipid levels, respectively. These inverse associations did not emerge in participants not taking these medications.
Among individuals with subclinical atherosclerosis, the unexpected inverse associations observed between change in blood pressure and lipid levels with CAC progression emphasize the importance of considering medication use, and, when feasible, the severity and duration of disease, in exploring associations between risk factors and CAC change.
PMCID: PMC4060615  PMID: 24698232
risk factors; coronary artery calcification; atherosclerosis
14.  Effects of timing, location and definition of reinfarction on mortality in patients with totally occluded infarct related arteries late after myocardial infarction 
Structured Abstract
The Occluded Artery Trial (OAT) randomized stable patients (n=2,201) >24 hours (calendar days 3–28) after myocardial infarction (MI) with totally occluded infarct-related arteries (IRA), to percutaneous coronary intervention (PCI) with optimal medical therapy, or optimal medical therapy alone (MED). PCI had no impact on the composite of death, reinfarction, or class IV heart failure over extended follow-up of up to 9 years. We evaluated the impact of early and late reinfarction and definition of MI on subsequent mortality.
Methods and Results
Reinfarction was adjudicated according to an adaptation of the 2007 universal definition of MI and the OAT definition (≥2 of the following - symptoms, EKG and biomarkers). Cox regression models were used to analyze the effect of post-randomization reinfarction and baseline variables on time to death.
After adjustment for baseline characteristics the 169 (PCI: n=95; MED: n=74) patients who developed reinfarction by the universal definition had a 4.15-fold (95% CI 3.03–5.69, p<0.001) increased risk of death compared to patients without reinfarction. This risk was similar for both treatment groups (interaction p=0.26) and when MI was defined by the stricter OAT criteria. Reinfarctions occurring within 6 months of randomization had similar impact on mortality as reinfarctions occurring later, and the impact of reinfarction due to the same IRA and a different epicardial vessel was similar.
For stable post-MI patients with totally occluded infarct arteries, reinfarction significantly independently increased the risk of death regardless of the initial management strategy (PCI vs. MED), reinfarction definition, location and early or late occurrence.
PMCID: PMC4067126  PMID: 24726166
Reinfarction; late revascularization; myocardial infarction; mortality
International journal of cardiology  2013;170(3):270-277.
The tachykinin, substance P, is found primarily in sensory nerves. In the heart, substance P-containing nerve fibers are often found surrounding coronary vessels, making them ideally situated to sense changes in the myocardial environment. Recent studies in rodents have identified substance P as having dual roles in the heart, depending on disease etiology and/or timing. Thus far, these studies indicate that substance P may be protective acutely following ischemia-reperfusion, but damaging long-term in non-ischemic induced remodeling and heart failure. Sensory nerves may be at the apex of the cascade of events leading to heart failure, therefore, they make a promising potential therapeutic target that warrants increased investigation.
PMCID: PMC4450674  PMID: 24286592
substance P; tachykinin; heart failure; neuropeptide; sensory nerve; myocardial remodeling
16.  Long-term Prognosis for Individuals with Hypertension Undergoing Coronary Artery Calcium Scoring 
To examine the performance of coronary artery calcification (CAC) for stratifying long-term risk of death in asymptomatic hypertensive patients.
Methods and Results
8905 consecutive asymptomatic individuals without cardiovascular disease or diabetes who underwent CAC testing (mean age 53.3±10.5, 59.3% male) were followed for a mean of 14 years and categorized on the background of hypertension (in accordance with the 2014 Guidelines from the Joint National Committee 8) as well as age above or below 60 years. The prevalence and severity of CAC was higher for those with versus without hypertension (P<0.001), and the extent increased proportionally with advancing age (P<0.001). Following adjustment, the presence of CAC in patients above and below the age of 60 years was associated with worse prognosis for hypertensive (HR 7.74 [95% CI: 5.15-11.63] and HR 3.18 [95% CI: 2.42-4.19]) and normotensive (HR 4.83 [95% CI: 3.18-7.33] and HR 2.14 [95% CI: 1.61-2.85]), respectively. A zero CAC score was associated with a lower but persisting risk of mortality for hypertensives over the age of 60 years (HR 2.48 [95% CI: 1.50-4.08]); albeit, attenuating for those below the age of 60 years (P=0.09). In a “low risk” hypertensive population, a combined presence of hypertension and any CAC was associated with an almost five-fold (HR 4.68 [95% CI: 2.22-9.87]) risk of death.
Among asymptomatic hypertensive individuals, the presence and extent of CAC effectively identified individuals at heightened risk of mortality beyond conventional cardiovascular risk.
PMCID: PMC4442064  PMID: 25863296
Coronary artery calcium; hypertension; all-cause mortality; cardiac computed tomography
17.  The benefits of neighborhood racial diversity: neighborhood factors and its association with increased physical activity in ACS patients 
International journal of cardiology  2014;173(3):517-518.
PMCID: PMC4031237  PMID: 24704399
Physical activity; acute coronary syndrome; neighborhood; racial diversity
18.  Beta-blockers in older patients with heart failure and preserved ejection fraction: class, dosage, and outcomes 
International journal of cardiology  2014;173(3):393-401.
We examined the clinical effectiveness of beta-blockers considered evidenced-based to heart failure and reduced ejection fraction (HFrEF) and recommended target dosing in older adults with HF and preserved ejection fraction (HFpEF).
In OPTIMIZE-HF (2003–2004) linked to Medicare (2003–2008), of the 10,570 older (age ≥65, mean, 81 years) adults with HFpEF (EF ≥40%, mean 55%), 8373 had no contraindications to beta-blocker therapy. After excluding 4614 patients receiving pre-admission beta-blockers, the remaining 3759 patients were potentially eligible for new discharge prescriptions for beta-blockers and 1454 received them. We assembled a propensity-matched cohort of 1099 pairs of patients receiving beta-blockers and no beta-blockers, balanced on 115 baseline characteristics. Evidence-based beta-blockers for HFrEF, namely, carvedilol, metoprolol succinate, and bisoprolol and their respective guideline-recommended target doses were 50, 200, and 10 mg/day.
During 6 years of follow-up, new discharge prescriptions for beta-blockers had no association with the primary composite endpoint of all-cause mortality or HF rehospitalization (hazard ratio, 1.03; 95% confidence interval {CI}, 0.94–1.13; p=0.569). This association did not vary by beta-blocker evidence class or daily dose. Hazard ratios for all-cause mortality and HF rehospitalization were 0.99 (95% CI, 0.90–1.10; p=0.897) and 1.17 (95% CI, 1.03–1.34; p=0.014). The latter association lost significance when higher EF cutoffs of ≥45%, ≥50% and ≥55% were used.
Initiation of therapy with beta-blockers considered evidence-based for HFrEF and in target doses recommended for HFrEF had no association with the composite or individual endpoints of all-cause mortality or HF rehospitalization in HFpEF.
PMCID: PMC4085276  PMID: 24703206
Beta-blockers; heart failure; preserved ejection fraction
19.  Aldehydic load and aldehyde dehydrogenase 2 profile during the progression of post-myocardial infarction cardiomyopathy: benefits of Alda-1 
We previously demonstrated that reducing cardiac aldehydic load by aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme responsible for metabolizing the major lipid peroxidation product, protects against acute ischemia/reperfusion injury and chronic heart failure. However, time-dependent changes in ALDH2 profile, aldehydic load and mitochondrial bioenergetics during progression of post-myocardial infarction (post-MI) cardiomyopathy is unknown and should be established to determine the optimal time window for drug treatment.
Here we characterized cardiac ALDH2 activity and expression, lipid peroxidation, 4-hydroxy-2-nonenal (4-HNE) adduct formation, glutathione pool and mitochondrial energy metabolism and H2O2 release during the 4 weeks after permanent left anterior descending (LAD) coronary artery occlusion in rats.
We observed a sustained disruption of cardiac mitochondrial function during the progression of post-MI cardiomyopathy, characterized by >50% reduced mitochondrial respiratory control ratios and up to 2 fold increase in H2O2 release. Mitochondrial dysfunction was accompanied by accumulation of cardiac and circulating lipid peroxides and 4-HNE protein adducts and down-regulation of electron transport chain complexes I and V. Moreover, increased aldehydic load was associated with a 90% reduction in cardiac ALDH2 activity and increased glutathione pool. Further supporting an ALDH2 mechanism, sustained Alda-1 treatment (starting 24hrs after permanent LAD occlusion surgery) prevented aldehydic overload, mitochondrial dysfunction and improved ventricular function in post-MI cardiomyopathy rats.
Taken together, our findings demonstrate a disrupted mitochondrial metabolism along with an insufficient cardiac ALDH2-mediated aldehyde clearance during the progression of ventricular dysfunction, suggesting a potential therapeutic value of ALDH2 activators during the progression of post-myocardial infarction cardiomyopathy.
PMCID: PMC4405147  PMID: 25464432
myocardial infarction; 4-hydroxinonenal; oxidative stress; bioenergetics; aldehyde dehydrogenase 2
20.  Epigenetic mechanisms underlying cardiac degeneration and regeneration* 
Epigenetic modifications which are defined by DNA methylation, histone modifications and microRNA mediated gene regulation, have been found to be associated with cardiac dysfunction and cardiac regeneration but the mechanisms are unclear. MicroRNA therapies have been proposed for cardiac regeneration and proliferation of stem cells into cardiomyocytes. Cardiovascular disorders are represented by abnormal methylation of CpG islands and drugs that inhibit DNA methyl transferases such as 5-methyl Aza cytidine are under trials. Histone modifications which include acetylation, methylation, phosphorylation, ADP ribosylation, sumoylation and biotinylation are represented within abnormal phenotypes of cardiac hypertrophy, cardiac development and contractility. MicroRNAs have been used efficiently to epigenetically reprogram fibroblasts into cardiomyocytes. MicroRNAs represent themselves as potential biomarkers for early detection of cardiac disorders which are difficult to diagnose and are captured at later stages. Because microRNAs regulate circadian genes, for example a nocturnin gene of circadian clockwork is regulated by mir122, they have profound role in regulating biological clock and this may explain the high cardiovascular risk during the morning time. This review highlights the role of epigenetics which can be helpful in disease management strategies.
PMCID: PMC3982321  PMID: 24636549
Epigenetics; stem cells; cardiomyocytes; microRNA; cardiac disorders; biomarkers
21.  Association of obesity and biomarkers of inflammation and endothelial dysfunction in adults in Inner Mongolia, China 
International journal of cardiology  2010;150(3):247-252.
Recent studies suggest that central obesity is an important predictor of cardiovascular disease (CVD) in addition to overall obesity. Both inflammation and endothelial dysfunction are associated with increased risk of CVD. We examined the association between body mass index (BMI) and waist circumference (WC) with plasma concentrations of biomarkers of inflammation and endothelial dysfunction.
We conducted a cross-sectional study of 2589 lean, moderately active participants aged 20 years and older in Inner Mongolia, China. Overnight fasting blood samples were obtained to measure the biomarkers including C-reactive protein (CRP), soluble inter-cellular adhesion molecule-1 (sICAM-1), soluble E-selectin (sE-selectin), and angiotensin II. Height, body weight, and WC were measured by trained staff and BMI was calculated (kg/m2).
In univariate analysis, CRP, sICAM-1, and sE-selectin were all significantly higher among individuals with a higher BMI and WC. In multivariate analysis, each standard deviation (SD) increase in WC (9.6 cm) was associated with about 46% higher risk (odds ratio [OR] 1.46, 95% confidence interval [CI] 1.21–1.76) of elevated CRP but a 1 SD increase in BMI (3.5 kg/m2) was not associated with the risk of elevated CRP (OR 0.96, 95% CI 0.80–1.16). However, each SD increase in BMI was associated with about 30% higher risk of having elevated E-selectin (OR 1.30, 95% CI 1.08–1.55).
WC is a stronger predictor of inflammation while BMI is a stronger predictor for endothelial dysfunction. These results suggest measuring both BMI and WC will help to assess the risk of CVD in the Chinese population.
PMCID: PMC4364655  PMID: 20439121
Inflammation; Endothelial dysfunction; C-reactive protein; Body mass index; Waist circumference
22.  Association of soy food intake with risk and biomarkers of coronary heart disease in Chinese men 
International journal of cardiology  2014;172(2):e285-e287.
PMCID: PMC3947738  PMID: 24438928
Soy foods; Coronary heart disease; Men; Prospective cohort study; Interleukin-8; Plasminogen activator inhibitor-1
24.  Framingham Score and LV Mass predict Events in Young Adults: CARDIA Study 
International journal of cardiology  2014;172(2):350-355.
Framingham risk score (FRS) underestimates risk in young adults. LV mass (LVM) relates to cardiovascular disease (CVD), with unclear value in youth. In a young biracial cohort, we investigate how FRS predicts CVD over 20 years and the incremental value of LVM. We also explore the predictive ability of different cut-points for hypertrophy.
We assessed FRS and echocardiography-derived LVM (indexed by BSA or height2.7) from 3980 African-American and white CARDIA participants (1990-1991); and followed over 20 years for a combined endpoint: cardiovascular death; nonfatal myocardial infarction, heart failure, cerebrovascular disease, and peripheral artery disease. We assessed the predictive ability of FRS for CVD and also calibration, discrimination, and net reclassification improvement for adding LVM to FRS.
Mean age was 30±4 years, 46% males, and 52% white. Event incidence (n = 118) across FRS groups was, respectively, 1.3%, 5.4%, and 23.1% (p<0.001); and was 1.4%, 1.3%, 3.7%, and 5.4% (p<0.001) across quartiles of LVM (cut-points 117g, 144g, and 176g). LVM predicted CVD independently of FRS, with the best performance in normal weight participants. Adding LVM to FRS modestly increased discrimination and had a statistically significant reclassification. The 85th percentile (≥116 g/m2 for men; ≥96 g/m2 for women) showed event prediction more robust than currently recommended cut-points for hypertrophy.
In a biracial cohort of young adults, FRS and LVM are helpful independent predictors of CVD. LVM can modestly improve discrimination and reclassify participants beyond FRS. Currently recommended cut-points for hypertrophy may be too high for young adults.
PMCID: PMC4068332  PMID: 24507735
young adults; cardiovascular risk; left ventricular hypertrophy; echocardiography
25.  Diagnosis of apical hypertrophic cardiomyopathy: T-wave inversion and relative but not absolute apical left ventricular hypertrophy☆ 
Diagnosis of apical HCM utilizes conventional wall thickness criteria. The normal left ventricular wall thins towards the apex such that normal values are lower in the apical versus the basal segments. The impact of this on the diagnosis of apical hypertrophic cardiomyopathy has not been evaluated.
We performed a retrospective review of 2662 consecutive CMR referrals, of which 75 patients were identified in whom there was abnormal T-wave inversion on ECG and a clinical suspicion of hypertrophic cardiomyopathy. These were retrospectively analyzed for imaging features consistent with cardiomyopathy, specifically: relative apical hypertrophy, left atrial dilatation, scar, apical cavity obliteration or apical aneurysm. For comparison, the same evaluation was performed in 60 healthy volunteers and 50 hypertensive patients.
Of the 75 patients, 48 met conventional HCM diagnostic criteria and went on to act as another comparator group. Twenty-seven did not meet criteria for HCM and of these 5 had no relative apical hypertrophy and were not analyzed further. The remaining 22 patients had relative apical thickening with an apical:basal wall thickness ratio > 1 and a higher prevalence of features consistent with a cardiomyopathy than in the control groups with 54% having 2 or more of the 4 features. No individual in the healthy volunteer group had more than one feature and no hypertension patient had more than 2.
A cohort of individuals exist with T wave inversion, relative apical hypertrophy and additional imaging features of HCM suggesting an apical HCM phenotype not captured by existing diagnostic criteria.
•The normal left ventricular myocardium tapers towards the apex.•There exists an apical HCM variant with relative rather than absolute apical hypertrophy.•T-wave inversion and relative apical hypertrophy are core features.•Additional features include a dilated left atrium, scarring, apical cavity obliteration and apical microaneurysms.
PMCID: PMC4392393  PMID: 25666123
Hypertrophic cardiomyopathy; Cardiovascular magnetic resonance

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