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1.  Amlodipine – Not a Significant Contributor to Clopidogrel Non-Response? 
Heart (British Cardiac Society)  2013;99(7):437-439.
PMCID: PMC4064296  PMID: 23315611
2.  Safety of serial MRI in patients with implantable cardioverter defibrillators 
Heart (British Cardiac Society)  2011;97(22):1852-1856.
While patients with cardiac implantable electronic devices could benefit from magnetic resonance (MR) imaging, the presence of such devices has been designated as an absolute contraindication to MR. Although scanning algorithms are proposed for cardiac implantable electronic devices, their safety remains uncertain. To address this issue, the safety of serial cardiac MR scans was evaluated in patients with implantable cardioverter defibrillators (ICDs).
Three serial cardiac MR scans were prospectively performed at 1.5 T on 10 patients (9 men) of median age 56 years (range 51–68) with ICDs. ICD interrogation was performed before and after the MR scan and at a follow-up of median 370 days (range 274–723). Image quality was also assessed.
In all patients MR scanning occurred without complications. There were no differences between preand post-MR pacing capture threshold, pacing lead or high voltage lead impedance, or battery voltage values. During follow-up there were no occurrences of ICD dysfunction. Although most patients had image artifacts, the studies were generally diagnostic regarding left ventricular function and wall motion. Delayed enhancement imaging was of good quality for inferior wall and inferolateral infarcts, but ICD artifacts often affected the imaging of anterior wall infarcts.
Serial MR scans at 1.5 T in patients with ICDs, when carefully performed in a monitored setting, have no adverse effects on either patient or device. When required, single or multiple MR scans at 1.5 T may therefore be considered for clinical diagnostic purposes in these patients.
PMCID: PMC3994993  PMID: 21873440
3.  Long-chain n-3 polyunsaturated fatty acids and incidence rate of coronary artery calcification in Japanese in Japan and United States whites – population-based prospective cohort study 
Heart (British Cardiac Society)  2013;100(7):569-573.
To determine whether serum levels of long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) contribute to the difference in incidence rate of coronary artery calcification (CAC) between Japanese in Japan and U.S. whites.
In a population-based prospective-cohort study, 214 Japanese and 152 white men aged 40–49 years at baseline (2002–2006) with coronary calcium score (CCS) = 0 were reexamined for CAC in 2007–2010. Among these, 175 Japanese and 113 whites participated in the follow-up exam. Incident cases were defined as participants with CCS ≥ 10 at follow-up. A relative risk regression analysis was used to model incidence rate ratio between Japanese and whites. The incidence rate ratio was first adjusted for potential confounders at baseline and then further adjusted for serum LCn3PUFAs at baseline.
Mean (standard deviation) serum percentage of LCn3PUFA was > 100% higher in Japanese than in whites (9.08 (2.49) versus 3.84 (1.79), respectively, p<0.01). Japanese had a significantly lower incidence rate of CAC compared to whites (0.9 versus 2.9/100 person-years, respectively, p < 0.01). Incidence rate ratio of CAC taking follow-up time into account between Japanese and white men was 0.321 (95% confidence interval (CI) 0.150, 0.690: p<0.01). After adjusting for age, systolic-blood pressure, low-density-lipoprotein cholesterol, diabetes, and other potential confounders, the ratio remained significant: 0.262 (95% CI: 0.094, 0.731, p=0.01). After further adjusting for LCn3PUFAs, however, the ratio was attenuated and became non-significant (0.376 (95% CI: 0.090, 1.572, p=0.18).
LCn3PUFAs significantly contributed to the difference in CAC incidence between Japanese and white men.
PMCID: PMC3949146  PMID: 24352736
long-chain n-3 fatty acids; coronary artery calcification; prospective cohort study; incidence; risk factors
4.  Palpitations in a 64 year old man 
Heart (British Cardiac Society)  2013;100(2):167-168.
PMCID: PMC3960282  PMID: 24281755
5.  Low-density lipoprotein and aortic stenosis 
Heart (British Cardiac Society)  2008;94(9):1111-1112.
PMCID: PMC3951852  PMID: 18703687
6.  Meta-analysis of secure randomised controlled trials of β-blockade to prevent perioperative death in non-cardiac surgery 
Heart  2013;100(6):456-464.
Current European and American guidelines recommend the perioperative initiation of a course of β-blockers in those at risk of cardiac events undergoing high- or intermediate-risk surgery or vascular surgery. The Dutch Echocardiographic Cardiac Risk Evaluation Applying Stress Echocardiography (DECREASE) family of trials, the bedrock of evidence for this, are no longer secure. We therefore conducted a meta-analysis of randomised controlled trials of β-blockade on perioperative mortality, non-fatal myocardial infarction, stroke and hypotension in non-cardiac surgery using the secure data.
The randomised controlled trials of initiation of β-blockers before non-cardiac surgery were examined. Primary outcome was all-cause mortality at 30 days or at discharge. The DECREASE trials were separately analysed.
Nine secure trials totalling 10 529 patients, 291 of whom died, met the criteria. Initiation of a course of β-blockers before surgery caused a 27% risk increase in 30-day all-cause mortality (p=0.04). The DECREASE family of studies substantially contradict the meta-analysis of the secure trials on the effect of mortality (p=0.05 for divergence). In the secure trials, β-blockade reduced non-fatal myocardial infarction (RR 0.73, p=0.001) but increased stroke (RR 1.73, p=0.05) and hypotension (RR 1.51, p<0.00001). These results were dominated by one large trial.
Guideline bodies should retract their recommendations based on fictitious data without further delay. This should not be blocked by dispute over allocation of blame. The well-conducted trials indicate a statistically significant 27% increase in mortality from the initiation of perioperative β-blockade that guidelines currently recommend. Any remaining enthusiasts might best channel their energy into a further randomised trial which should be designed carefully and conducted honestly.
PMCID: PMC3932762  PMID: 23904357
7.  Associations of vitamin D, parathyroid hormone and calcium with cardiovascular risk factors in US adolescents 
Heart (British Cardiac Society)  2010;97(4):315-320.
To examine independent associations of serum 25-hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and calcium with a range of cardiovascular risk factors in adolescents.
Cross-sectional population-based study.
A nationally representative sample of the US adolescent population.
Healthy adolescents (aged 12–19) participating in the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2006. Numbers varied between 740 and 5609 for given exposure and outcome associations.
Main outcome measures
Systolic blood pressure (SBP), diastolic blood pressure (DBP), lipids (triglycerides, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)), fasting insulin and glucose, postload glucose and glycohaemoglobin (HbA1c).
25(OH)D was inversely associated with SBP (−0.068 standard deviations (SD), 95% CI −0.118 to −0.018), and positively associated with HDL-C (0.101; 0.040 to 0.162) and HbA1c (0.073; 0.021 to 0.125) after adjustment for gender, age, ethnicity, socioeconomic status and waist circumference. In adjusted models, PTH was inversely associated with triglycerides (−0.115; −0.188 to −0.042) and LDL-C (−0.133; −0.207 to −0.060). In adjusted models, calcium was positively associated with fasting insulin (0.110; 0.060 to 0.160), postload glucose (0.116; 0.000 to 0.232), HbA1c (0.079; 0.035 to 0.123), triglycerides (0.182; 0.122 to 0.242), HDL-C (0.049; 0.010 to 0.088) and LDL-C (0.137; 0.080 to 0.195). The associations of each exposure with risk factors remained after mutual adjustment for each other.
Higher calcium levels might be a more important predictor of increased cardiovascular risk in adolescents than lower 25(OH)D levels or PTH levels, but the findings require replication in additional studies and examination in prospective studies.
PMCID: PMC3931194  PMID: 21193684
8.  Preeclampsia and maternal placental syndromes: An indicator of a predisposition or cause of long-term cardiovascular disease? 
Heart (British Cardiac Society)  2012;98(15):1109-1111.
PMCID: PMC3925666  PMID: 22698857
Hypertension; Pregnancy induced; Placenta Diseases; Heart failure; Arrhythmias; cardiac
9.  Bile acids induce arrhythmias: old metabolite, new tricks 
Heart (British Cardiac Society)  2013;99(22):1629-1630.
PMCID: PMC3913276  PMID: 23969477
10.  Smoking water-pipe, chewing nass, and prevalence of heart disease – A cross-sectional analysis of baseline data from the Golestan Cohort Study, Iran 
Heart (British Cardiac Society)  2012;99(4):272-278.
Water-pipe and smokeless tobacco use have been associated with several adverse health outcomes. However, little information is available on the association between water-pipe use and heart disease (HD). Therefore, we investigated the association of smoking water-pipe and chewing nass (a mixture of tobacco, lime, and ash) with prevalent HD.
Cross-sectional study.
Baseline data (collected in 2004–2008) from a prospective population-based study in Golestan Province, Iran.
50,045 residents of Golestan (40–75 years old; 42.4% male).
Main outcome measures
ORs and 95% CIs from multivariate logistic regression models for the association of water-pipe and nass use with HD prevalence.
A total of 3051 (6.1%) participants reported a history of HD, and 525 (1.1%) and 3726 (7.5%) reported ever water-pipe or nass use, respectively. Heavy water-pipe smoking was significantly associated with HD prevalence (highest level of cumulative use versus never use, OR= 3.75; 95% CI 1.52 – 9.22; P for trend= 0.04). This association persisted when using different cutoff points, when restricting HD to those taking nitrate compound medications, and among never cigarette smokers. There was no significant association between nass use and HD prevalence (highest category of use versus never use, OR= 0.91; 95% CI 0.69 – 1.20).
Our study suggests a significant association between HD and heavy water-pipe smoking. Although the existing evidence suggesting similar biological consequences of water-pipe and cigarette smoking make this association plausible, results of our study were based on a modest number of water-pipe users and need to be replicated in further studies.
PMCID: PMC3671096  PMID: 23257174
hookah; ischemic heart disease; nass; tobacco; water-pipe
11.  Multiple cardiovascular risk factors in Kenya: evidence from a Health and Demographic Surveillance System using the WHO STEPwise Approach to Chronic Disease Risk Factor Surveillance 
Heart (British Cardiac Society)  2013;99(18):1323-1329.
To describe the distribution of cardiovascular risk factors in western Kenya using a Health and Demographic Surveillance System (HDSS).
Population-based survey of residents in an HDSS
Webuye Division in Bungoma East District, Western Province of Kenya
4037 adults ≥18 years of age
Home-based survey using the World Health Organization STEPwise approach to chronic disease risk factor surveillance
Main outcome measures
Self-report of high blood pressure, high blood sugar, tobacco use, alcohol use, physical activity and fruit/vegetable intake
The median age of the population was 35 years (IQR: 26–50). Less than 6% of the population reported high blood pressure or blood sugar. Tobacco and alcohol use were reported in 7% and 16% of the population, respectively. The majority of the population (93%) was physically active. The average number of days per week that participants reported intake of fruits (3.1 +/− 0.1) or vegetables (1.6 +/− 0.1) was low. In multiple logistic regression analyses, women were more likely to report a history of high blood pressure (OR 2.72, 95% CI 1.9–3.9), less likely to report using tobacco (OR 0.08, 95% CI 0.06–0.11), less likely to report alcohol use (OR 0.18, 95% CI 0.15–0.21) or eat ≥5 servings per day of fruits or vegetables (OR 0.87, 95% CI 0.76–0.99) compared to men.
The most common cardiovascular risk factors in peri-urban western Kenya are tobacco use, alcohol use and inadequate intake of fruits and vegetables. Our data reveal locally-relevant sub-group differences that could inform future prevention efforts.
PMCID: PMC3898037  PMID: 23872588
cardiovascular diseases; risk factors; Kenya; demography; sub-Saharan Africa
12.  Future applications of contrast echocardiography 
Heart (British Cardiac Society)  2012;98(3):10.1136/heartjnl-2011-300737.
PMCID: PMC3856916  PMID: 22199019
13.  Speckle myocardial imaging modalities for early detection of myocardial impairment in isolated left ventricular non-compaction 
Heart (British Cardiac Society)  2009;96(6):10.1136/hrt.2009.182170.
To examine the hypothesis that speckle myocardial imaging (SMI) modalities, including longitudinal, radial and circumferential systolic (s) and diastolic (d) myocardial velocity imaging, displacement (D), strain rate (SR) and strain (S), as well as left ventricular (LV) rotation/torsion are sensitive for detecting early myocardial dysfunction in isolated LV non-compaction (iLVNC).
Design and results
Twenty patients with iLVNC diagnosed by cardiac magnetic resonance (15) or echocardiography (5) were included. Patients were divided into two groups: ejection fraction (EF)>50% (n=10) and EF≤50% (n=10). Standard measures of systolic and diastolic function including pulsed wave tissue Doppler Imaging (PWTDI) were obtained. Longitudinal, radial and circumferential SMI, and LV rotation/torsion were compared with values for 20 age/sex-matched controls. EF, PWTDI E′, E/E′ and all of the SMI modalities were significantly abnormal for patients with EF≤50% compared with controls. In contrast, EF and PWTDI E′, E/E′ were not significantly different between controls and patients with iLVNC (EF>50%). However, SMI-derived longitudinal sS, sSR, sD and radial sS, as well as LV rotation/torsion values, were all reduced in iLVNC (EF>50%) compared with controls. Measurements with the highest discriminating power between iLVNC (EF>50%) and controls were longitudinal sS mean of the six apical segments (area under the curve (AUC)=0.94), sS global average (AUC=0.94), LV rotation apical mean (AUC=0.94); LV torsion (AUC=0.93) LV torsion rate (AUC=0.94).
LV SMI values are reduced in patients with iLVNC, even those with normal EF and PWTDI. The most accurate SMI modalities to discriminate between patients and controls are longitudinal sS mean of the six apical segments, LV apical rotation or LV torsion rate.
PMCID: PMC3835601  PMID: 19966109
14.  Low-dose nesiritide in human anterior myocardial infarction suppresses aldosterone and preserves ventricular function and structure: a proof of concept study 
Heart (British Cardiac Society)  2009;95(16):10.1136/hrt.2008.153916.
B-type natriuretic peptide (BNP, nesiritide) has anti-fibrotic, anti-hypertrophic, anti-inflammatory, vasodilating, lusitropic and aldosterone-inhibiting properties but conventional doses of BNP cause hypotension, limiting its use in heart failure.
To determine whether infusion of low-dose BNP within 24 h of successful reperfusion for anterior acute myocardial infarction (AMI) would prevent adverse left ventricular (LV) remodelling and suppress aldosterone.
A translational proof-of-concept study was carried out to determine tolerability and biological activity of intravenous BNP at 0.003 and 0.006 mg/kg/min, without bolus started within 24 h of successful reperfusion for anterior AMI. 24 patients with first anterior wall ST elevation AMI and successful revascularisation were randomly assigned to receive 0.003 (n = 12) or 0.006 (n = 12) mg/kg/min of IV BNP for 72 h in addition to standard care during hospitalisation for anterior AMI.
Baseline characteristics, drugs and peak cardiac biomarkers for myocardial damage were similar between both groups. Infusion of BNP at 0.006 mg/kg/min resulted in greater biological activity than infusion at 0.003 mg/kg/min as measured by higher mean (SEM) plasma cGMP levels (8.6 (1) vs 5.5 (1) pmol/ml, p,0.05) and suppression of plasma aldosterone (8.0 (2) to 4.6 (1) ng/ dl, p,0.05), which was not seen in the 0.003 mg/kg/min group. LV ejection fraction (LVEF) improved significantly from baseline to 1 month (40 (4)% to 54 (5)%, p,0.05) in the 0.006 group but not in the 0.003 group. Infusion of BNP at 0.006 mg/kg/min was associated with a decrease of LV end-systolic volume index (61 (9) to 43 (8) ml/m2, p,0.05) at 1 month, which was not seen in the 0.003 group. No drug-related serious adverse events occurred in either group.
72 h infusion of low BNP at the time of anterior AMI is well tolerated and biologically active. Patients treated with low-dose BNP had improved LVEF and smaller LV end-systolic volume at 1 month.
PMCID: PMC3835541  PMID: 19447837
15.  Changes in HDL cholesterol and cardiovascular outcomes after lipid modification therapy 
Heart (British Cardiac Society)  2012;98(10):780-785.
Lipid modification therapy (LMT) produces cardiovascular benefits principally through reductions in low density lipoprotein cholesterol (LDL-C). While recent evidence, using data from 454 participants in the Framingham Offspring Study (FOS), has suggested that increases in high density lipoprotein cholesterol (HDL-C) are also associated with a reduction in cardiovascular outcomes, independently of changes in LDL-C, replication of this finding is important. We therefore present further results using data from the EPIC Norfolk (UK) and Rotterdam (Netherlands) prospective cohort studies.
A total of 1,148 participants, 446 from the EPIC-Norfolk and 702 from the Rotterdam study were assessed for lipids before and after starting LMT. Subsequent risk of cardiovascular events, ascertained through linkage with mortality records and hospital databases, was investigated using Cox Proportional hazards regression. Random effects meta-analysis was used to combine results across studies.
Based on combined data from the EPIC-Norfolk and Rotterdam studies there was some evidence that change in HDL-C resulting from LMT was associated with reduced cardiovascular risk (hazard ratio per pooled SD (= 0. 34 mmol/l) increase = 0.74, 95% CI 0.56-0.99, adjusted for age, sex, and baseline HDL-C). However, this association was attenuated and was not (statistically) significant with further adjustments for non-HDL-C and for cigarette smoking history, prevalent diabetes, SBP, BMI, use of antihypertensive medication, previous MI, prevalent angina, previous stroke (0.92, 0.70-1.20).
Following adjustment for conventional non-lipid CVD risk factors, this study provides no evidence to support a significant benefit from increasing HDL-C independent of the effect of lowering non-HDL-C.
PMCID: PMC3773905  PMID: 22447463
Lipids; Lipoproteins; HDL; Atherosclerosis; Myocardial infarction
16.  Family history of premature coronary heart disease and risk prediction in the EPIC-Norfolk prospective population study 
Heart (British Cardiac Society)  2010;96(24):1985-1989.
The value of a family history for coronary heart disease (CHD) in addition to established cardiovascular risk factors in predicting an individual’s risk of CHD is unclear. In the EPIC-Norfolk cohort, we tested whether adding family history of premature CHD in first degree relatives improves risk prediction compared to the Framingham risk score (FRS) alone.
Methods and Results
This study comprised 10,288 men and 12,553 women aged 40 to 79 years participating in the EPIC-Norfolk cohort who where followed for an average of 10.9 ± 2.1 years (mean ± SD). We computed the Framingham risk score as well as a modified score taking into account family history of premature CHD. A family history of CHD was indeed associated with an increased risk of future CHD, independent of established risk factors (FRS-adjusted hazard ratio of 1.74 (95%CI 1.56-1.95) for family history of premature CHD). However, adding family history of CHD to the Framingham risk score resulted in a negative net reclassification of 2%. In the subgroup of individuals estimated to be at intermediate risk, family history of premature CHD resulted in an increase in net reclassification of 2%. The sensitivity increased with 0.4 % and the specificity decreased 0.8%.
Although family history of CHD was an independent risk factor of future CHD, its use did not improve classification of individuals into clinically relevant risk categories based on the FRS. Among study participants at intermediate risk of CHD, adding family history of premature CHD resulted in, at best, a modest improvement in reclassification of individuals into a more accurate risk category.
PMCID: PMC3773915  PMID: 20962344
17.  Diastolic Relaxation and Compliance Reserve during Dynamic Exercise in Heart Failure with Preserved Ejection Fraction 
Heart (British Cardiac Society)  2011;97(12):964-969.
Recent studies have examined hemodynamic changes with stressors such as isometric handgrip and rapid atrial pacing in heart failure with preserved ejection fraction (HFpEF), but little is known regarding left ventricular (LV) pressure-volume responses during dynamic exercise.
Assess LV hemodynamic responses to dynamic exercise in patients with HFpEF.
Methods and Results
Twenty subjects with normal EF and exertional dyspnea underwent invasive hemodynamic assessment during dynamic exercise to evaluate for suspected HFpEF. LV end-diastolic pressure (LVEDP) was elevated at rest (>15mmHg, n=18) or with exercise (≥20mmHg, n=20) in all, consistent with HFpEF. Heart rate, blood pressure, arterial elastance and cardiac output increased with exercise (all p<0.001). Minimal and mean LV diastolic pressures increased by 43–56% with exercise (both p<0.0001), despite a trend toward reduction in LV end-diastolic volume (p=0.08). Diastolic filling time was abbreviated with increases in heart rate, and the proportion of diastole that elapsed prior to estimated complete relaxation increased (p<0.0001), suggesting inadequate relaxation reserve relative to the shortening of diastole. LV diastolic chamber elastance acutely increased 50% during exercise (p=0.0003). Exercise increases in LV filling pressures correlated with changes in diastolic relaxation rates, chamber stiffness and arterial afterload but were not related to alterations in preload volume, heart rate, or cardiac output.
In patients with newly-diagnosed HFpEF, LV filling pressures increase during dynamic exercise in association with inadequate enhancement of relaxation and acute increases in LV chamber stiffness. Therapies that enhance diastolic reserve function may improve symptoms of exertional intolerance in patients with hypertensive heart disease and early HFpEF.
PMCID: PMC3767403  PMID: 21478380
Heart Failure; Diastolic Dysfunction; Haemodynamics; Exercise; Old Age
18.  Ischaemic Symptoms, Quality of Care, and Mortality during Myocardial Infarction 
In myocardial infarction (MI), we studied whether documentation of ischemic symptoms is associated with quality of care and outcomes, and compared patient reports of ischaemic symptoms during interviews with chart documentation
Observational acute myocardial infarction study from 2003–2004 (Prospective Registry Evaluating Myocardial Infarction: Event and Recovery)
19 diverse US hospitals
2,094 consecutive MI patients (10,911 patients screened; 3,953 patients were eligible and enrolled) with both positive cardiac enzymes and other evidence of infarction (e.g., symptoms, electrocardiographic changes). Transferred patients and those with confounding noncardiac comorbidity were not included (n=1859).
Main outcome measures
Quality of care indicators and adjusted in-hospital survival
The records of 10% of all MI patients (217/2094) contained no documented ischaemic symptoms at presentation. Patients without documented symptoms were less likely (p<0.05) to: receive aspirin (89% vs. 96%) or beta-blockers (77% vs. 90%) within 24hr, reperfusion therapy for STEMI (7% vs. 58%) or to survive their hospitalization (adjusted OR=3.2, 95% CI 1.8–5.8). Survivors without documented symptoms were also less likely (p<0.05) to be discharged with aspirin (87% vs. 93%), beta-blockers (81% vs. 91%), ACE/ARB (67% vs. 80%), or smoking cessation counseling (46% vs. 66%). In the subset of 1,356 (65%) interviewed patients, most of those without documented ischaemic symptoms (75%) reported presenting symptoms consistent with ischaemia.
Failure to document patients’ presenting MI symptoms is associated with poorer quality of care from admission to discharge, and higher in-hospital mortality. Symptom recognition may represent an important opportunity to improve the quality of MI care.
PMCID: PMC3703470  PMID: 17639097
19.  What can adiponectin say about left ventricular function? 
Heart (British Cardiac Society)  2009;96(5):331-332.
PMCID: PMC3673540  PMID: 19934101
20.  Systolic Blood Pressure and Incident Heart Failure in the Elderly 
Heart (British Cardiac Society)  2011;97(16):1304-1311.
The exact form of the association between systolic blood pressure (SBP) and heart failure (HF) risk in the elderly remains incompletely defined, especially in individuals not receiving antihypertensive medications. Our aim was to examine the association between SBP and HF risk in the elderly.
Competing-risks proportional hazards modeling of incident HF risk, utilizing 10-year follow-up data from two NIH-sponsored cohort studies; the Cardiovascular Health Study (inception: 1989-90 and 1992-93) and the Health ABC Study (inception: 1997-98).
Community-based cohorts.
4408 participants (age, 72.8 [4.9] years; 53.1% women, 81.7% white; 18.3% black) without prevalent HF and not receiving antihypertensive medications at baseline.
Main outcome measures
Incident HF, defined as first adjudicated hospitalisation for HF.
Over 10 years, 493 (11.1%) participants developed HF. Prehypertension (120-139 mmHg), stage 1 (140-159 mmHg), and stage 2 (≥160 mmHg) hypertension were associated with escalating HF risk; hazard ratios vs. optimal SBP (<120 mmHg) in competing-risks models controlling for clinical characteristics were 1.63 (95% CI, 1.23-2.16; P=0.001), 2.21 (95% CI, 1.65-2.96; P<0.001), and 2.60 (95% CI, 1.85-364; P<0.001), respectively. Overall 255 of 493 (51.7%) HF events occurred in participants with SBP <140 mm Hg at baseline. Increasing SBP was associated with higher HF risk in women than men; no race-SBP interaction was observed. In analyses with continuous SBP, HF risk had a continuous positive association with SBP to levels as low as 113 mmHg in men and 112 mmHg in women.
There is a continuous positive association between SBP and HF risk in the elderly for levels of SBP as low as <115 mmHg; over half of incident HF events occur in individuals with SBP <140 mmHg.
PMCID: PMC3652313  PMID: 21636845
epidemiology; hypertension; heart failure; risk stratification
21.  Antioxidant therapy for atrial fibrillation: lost in translation? 
Heart (British Cardiac Society)  2012;98(22):1615-1616.
PMCID: PMC3651833  PMID: 22895646
22.  [No title available] 
PMCID: PMC3638973  PMID: 21775508
23.  Loss to specialist follow-up in congenital heart disease; out of sight, out of mind 
Heart  2013;99(7):485-490.
To evaluate the scale and clinical importance of loss to follow-up of past patients with serious congenital heart disease, using a common malformation as an example. To better understand the antecedents of loss to specialist follow-up and patients’ attitudes to returning.
Cohort study using NHS number functionality. Content and thematic analysis of telephone interviews of subset contacted after loss to follow-up.
Patients, intervention and setting
Longitudinal follow-up of complete consecutive list of all 1085 UK patients with repair of tetralogy of Fallot from single institution 1964–2009.
Main outcome measures
Survival, freedom from late pulmonary valve replacement, loss to specialist follow-up, shortfall in late surgical revisions related to loss to follow-up. Patients’ narrative about loss to follow-up.
216 (24%) of patients known to be currently alive appear not to be registered with specialist clinics; some are seen in general cardiology clinics. Their median age is 32 years and median duration of loss to follow-up is 22 years; most had been lost before Adult Congenital services had been consolidated in their present form. 48% of the late deaths to date have occurred in patients not under specialist follow-up. None of those lost to specialist follow-up has had secondary pulmonary valve replacement while 188 patients under specialist care have. Patients lost to specialist follow-up who were contacted by telephone had no knowledge of its availability.
Loss to specialist follow-up, typically originating many years ago, impacts patient management.
PMCID: PMC3595142  PMID: 23257171
24.  Competing cardiovascular outcomes associated with electrocardiographic left ventricular hypertrophy: the Atherosclerosis Risk in Communities study 
Heart (British Cardiac Society)  2011;98(4):330-334.
Individuals with electrocardiographically-determined left ventricular hypertrophy (ECG LVH) are at risk for multiple cardiovascular disease (CVD) outcomes simultaneously. We sought to characterize the competing incidences for subtypes of first CVD events or non-CVD death in those with and without ECG LVH.
We included participants in the Atherosclerosis Risk in Communities (ARIC) study. ECG LVH was defined according to Sokolow-Lyon criteria. We used competing Cox models to compare hazards for diverse outcomes within groups (e.g., among those with ECG LVH) and for a given event between groups (ECG LVH versus no ECG LVH).
After 15 years, men with ECG LVH at baseline (N = 383) had cumulative incidence of first CVD events and non-CVD deaths of 29.2% and 6.1%, respectively (hazard ratio 4.86; 95% CI, 3.04–7.77). In men without ECG LVH (N = 6576) the incidence of any first CVD event and non-CVD death was 18.9% and 6.9%, respectively (hazard ratio 2.67; 2.39–2.98). Similar associations were observed in women (N = 381 with and N = 8187 without ECG LVH). Coronary heart disease (CHD) was the most common first event in men with ECG LVH (15.0%) and heart failure (HF) was the most common first event in women with ECG LVH (10.5%). After adjustment for risk factors including systolic blood pressure, any CVD event remained the most likely first event.
Among middle-aged individuals with ECG LVH, the most likely first events are CHD in men and HF in women; these results may have implications for preventive approaches.
PMCID: PMC3569012  PMID: 22139711
left ventricular hypertrophy; cardiovascular disease; coronary heart disease; stroke; heart failure
25.  Tubular damage in chronic systolic heart failure is associated with reduced survival independent of glomerular filtration rate 
Heart (British Cardiac Society)  2010;96(16):1297-1302.
The prognostic impact of reduced glomerular filtration rate (GFR) in chronic heart failure (CHF) is increasingly recognised, but little is known about tubular damage in these patients.
To investigate the prevalence of tubular damage, and its association with GFR, and prognosis in patients with CHF.
Methods and results
In 90 patients with CHF, GFR and effective renal plasma flow (ERPF) were measured ([125I] iothalamate and [131I]hippuran clearances). The tubular markers neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG) and kidney injury molecule 1 (KIM-1) as well as urinary albumin excretion were determined in 24 h urine collections. Mean GFR was 78±26 ml/min/1.73 m2. Urinary NGAL (175 (70—346) mg/g creatinine (gCr)), NAG (12 (6—17) U/gCr) and KIM-1 (277 (188—537) ng/gCr) levels were increased compared with 20 healthy controls (all p<0.001). Urinary NAG, but not NGAL or KIM-1 correlated with GFR (r=−0.34, p=0.001) and ERPF (r=−0.29, p=0.006). Both NAG (r=0.21, p=0.048) and KIM-1 (r=0.23, p=0.033) correlated with plasma N-terminal pro-brain natriuretic peptide levels. Both urinary KIM-1 (HR=1.15 (95% CI 1.02 to 1.30) per 100 ng/gCr increase, p=0.025) and NAG (HR=1.42 (95% CI 1.02 to 1.94) per 5 U/gCr increase, p=0.039), were associated with an increased risk of death or heart failure hospitalisations, independent of GFR.
Tubular damage, as indicated by increased urinary concentrations of NGAL, NAG and KIM-1 is common in patients with CHF and mildly reduced GFR. Both urinary KIM-1 and NAG showed prognostic information additional to GFR. These findings suggest an important role for tubular damage and tubular markers in cardiorenal interaction in heart failure.
PMCID: PMC3480323  PMID: 20659949

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