Sex differences in coronary atherosclerotic plaque activity using 18F-sodium fluoride positron emission tomography.

INTRODUCTION: There are sex differences in the extent, severity, and outcomes of coronary artery disease. We aimed to assess the influence of sex on coronary atherosclerotic plaque activity measured using coronary 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), and to determine whether 18F-NaF PET has prognostic value in both women and men. METHODS: In a post-hoc analysis of observational cohort studies of patients with coronary atherosclerosis who had undergone 18F-NaF PET CT angiography, we compared the coronary microcalcification activity (CMA) in women and men. RESULTS: Baseline 18F-NaF PET CT angiography was available in 999 participants (151 (15%) women) with 4282 patient-years of follow-up. Compared to men, women had lower coronary calcium scores (116 [interquartile range, 27-434] versus 205 [51-571] Agatston units; p = 0.002) and CMA values (0.0 [0.0-1.12] versus 0.53 [0.0-2.54], p = 0.01). Following matching for plaque burden by coronary calcium scores and clinical comorbidities, there was no sex-related difference in CMA values (0.0 [0.0-1.12] versus 0.0 [0.0-1.23], p = 0.21) and similar proportions of women and men had no 18F-NaF uptake (53.0% (n = 80) and 48.3% (n = 73); p = 0.42), or CMA values > 1.56 (21.8% (n = 33) and 21.8% (n = 33); p = 1.00). Over a median follow-up of 4.5 [4.0-6.0] years, myocardial infarction occurred in 6.6% of women (n = 10) and 7.8% of men (n = 66). Coronary microcalcification activity greater than 0 was associated with a similarly increased risk of myocardial infarction in both women (HR: 3.83; 95% CI:1.10-18.49; p = 0.04) and men (HR: 5.29; 95% CI:2.28-12.28; p < 0.001). CONCLUSION: Although men present with more coronary atherosclerotic plaque than women, increased plaque activity is a strong predictor of future myocardial infarction regardless of sex.

Remote ischemic preconditioning in human coronary artery bypass surgery: from promise to disappointment?

BACKGROUND: We assessed whether remote ischemic preconditioning (RIPC) improves myocardial, renal, and lung protection after on-pump coronary surgery. METHODS AND RESULTS: This was a single-center, prospective, randomized (1:1), placebo-controlled trial. Patients, investigators, anesthetists, surgeons, and critical care teams were blinded to group allocation. Subjects received RIPC (or placebo) stimuli (×3 upper limb (or dummy arm), 5-minute cycles of 200 mm Hg cuff inflation/deflation) before aortic clamping. Anesthesia, perfusion, cardioplegia, and surgical techniques were standardized. The primary end point was 48-hour area under the curve (AUC) troponin T (cTnT) release. Secondary end points were 6-hour and peak cTnT, ECG changes, cardiac index, inotrope and vasoconstrictor use, renal dysfunction, and lung injury. Hospital survival was 99.4%. Comparing placebo and RIPC, median (interquartile range) AUC 48-hour cTnT (ng/mL(-1)/48 h(-1)); 28 (19, 39) versus 30 (22, 38), 6-hour cTnT (ng/mL(-1)); 0.93(0.59, 1.35) versus 1.01(0.72, 1.43), peak cTnT (ng/mL(-1)); 1.02 (0.74, 1.44) versus 1.04 (0.78, 1.51), de novo left bundle-branch block (4% versus 0%) and Q waves (5.3% versus 5.5%), serial cardiac indices, intraaortic balloon pump usage (8.5% versus 7.5%), inotrope (39% versus 50%) and vasoconstrictor usage (66% versus 64%) were not different. Dialysis requirement (1.2% versus 3.8%), peak creatinine (median [interquartile range], 1.2 mg/dL(-1) (1.1, 1.4) versus 1.2 (1.0, 1.4)), and AUC urinary albumin-creatinine ratios 69 (40, 112) versus 58 (32, 85) were not different. Intubation times; median (interquartile range), 937 minutes(766, 1402) versus 895(675, 1180), 6-hour; 278 (210, 338) versus 270 (218, 323) and 12-hour pO(2):FiO(2) ratios 255 (195, 323) versus 263 (210, 308) were similar. CONCLUSIONS: In contrast to prior smaller studies, RIPC did not reduce troponin release, improve hemodynamics, or enhance renal or lung protection. Clinical Trial Registration-URL: http://www.ukcrn.org.uk. Unique identifier: 4659.

Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts.

We studied here the independent associations of estimated glomerular filtration rate (eGFR) and albuminuria with mortality and end-stage renal disease (ESRD) in individuals with chronic kidney disease (CKD). We performed a collaborative meta-analysis of 13 studies totaling 21,688 patients selected for CKD of diverse etiology. After adjustment for potential confounders and albuminuria, we found that a 15 ml/min per 1.73 m² lower eGFR below a threshold of 45 ml/min per 1.73 m² was significantly associated with mortality and ESRD (pooled hazard ratios (HRs) of 1.47 and 6.24, respectively). There was significant heterogeneity between studies for both HR estimates. After adjustment for risk factors and eGFR, an eightfold higher albumin- or protein-to-creatinine ratio was significantly associated with mortality (pooled HR 1.40) without evidence of significant heterogeneity and with ESRD (pooled HR 3.04), with significant heterogeneity between HR estimates. Lower eGFR and more severe albuminuria independently predict mortality and ESRD among individuals selected for CKD, with the associations stronger for ESRD than for mortality. Thus, these relationships are consistent with CKD stage classifications based on eGFR and suggest that albuminuria provides additional prognostic information among individuals with CKD.

Glucose-insulin-potassium and tri-iodothyronine individually improve hemodynamic performance and are associated with reduced troponin I release after on-pump coronary artery bypass grafting.

BACKGROUND: Both glucose-insulin-potassium (GIK) and tri-iodothyronine (T3) may improve cardiovascular performance after coronary artery surgery (CABG) but their effects have not been directly compared and the effects of combined treatment are unknown. METHODS AND RESULTS: In 2 consecutive randomized double-blind placebo-controlled trials, in patients undergoing first time isolated on-pump CABG between January 2000 and September 2004, 440 patients were recruited and randomized to either placebo (5% dextrose) (n=160), GIK (40% dextrose, K+ 100 mmol.L(-1), insulin 70 u.L(-1)) (0.75 mL.kg(-1) h(-1)) (n=157), T3 (0.8 microg.kg(-1) followed by 0.113 microg.kg(-1) h(-1)) (n=63) or GIK+T3 (n=60). GIK/placebo therapy was administered from start of operation until 6 hours after removal of aortic cross-clamp (AXC) and T3/placebo was administered for a 6-hour period from removal of AXC. Serial hemodynamic measurements were taken up to 12 hours after removal of AXC and troponin I (cTnI) levels were assayed to 72 hours. Cardiac index (CI) was significantly increased in both the GIK and GIK/T3 group in the first 6 hours compared with placebo (P<0.001 for both) and T3 therapy (P=0.009 and 0.029, respectively). T3 therapy increased CI versus placebo between 6 and 12 hours after AXC removal (P=0.01) but combination therapy did not. Release of cTnI was lower in all treatment groups at 6 and 12 hours after removal of AXC. CONCLUSIONS: Treatment with GIK, T3, and GIK/T3 improves hemodynamic performance and results in reduced cTnI release in patients undergoing on-pump CABG surgery. Combination therapy does not provide added hemodynamic effect.

The effects of hypothermia on human left ventricular contractile function during cardiac surgery.

OBJECTIVES: We investigated the interaction of heart rate (HR), temperature and contractility using a validated load independent method. BACKGROUND: Temperature manipulation is an integral part of cardiac surgery, and postoperative hypothermia is extremely common. Myocardial contraction is a series of enzymatic and physico-chemical reactions that may be differentially affected by temperature. METHODS: Ten patients undergoing coronary artery bypass grafting were studied during moderately hypothermic cardiopulmonary bypass. After conduit procurement and heparinization but before grafting, the patient was placed on cardiopulmonary bypass and rewarmed to 37 degrees C, and the left ventricle (LV) was instrumented with a conductance catheter allowing continuous pressure and volume measurement. The LV pressure volume relationship was examined to assess the contractility at 37, 35, 33 and 31 degrees C, with fixed atrial pacing (100 beats/min) in five patients and at 80 and 120 beats/min, at 33 and 37 degrees C in five patients. RESULTS: At a HR of 100 beats/min, lower temperature resulted in a highly significant decrease in maximal elastance (100% at 37 degrees C, 29 +/- 3.5% at 31 degrees C, p < 0.0001). At 37 degrees C, increasing HR increased contractility (80 beats/min 100%, 120 beats/min 205.9%, p = 0.0021); however, at 33 degrees C contractility fell with increasing HR (80 beats/min 100%, 120 beats/min, 53.7%, p = 0.0014). CONCLUSIONS: At normothermia LV contractility has a direct relationship with HR. In hypothermic conditions this relationship inverses. Clinical strategies maintaining higher HRs at colder temperatures result in reduced contractility. These factors are important in the management of cardiac surgical patients.

Successful treatment of a radial artery pseudoaneurysm in an octogenarian.

The transradial approach for coronary catheterisation has gained rising popularity owing to its fewer access site complications compared with the transfemoral approach. A rare but recognisable complication of the procedure is radial artery pseudoaneurysm (PSA). We report a case of radial PSA occurring 2 h following percutaneous coronary intervention in an 85-year-old woman, which was successfully treated by ultrasound-guided thrombin injection. This non-surgical technique has recently gained rising popularity as a relatively novel modality of managing radial PSA.

Myocardial strain measurement with feature-tracking cardiovascular magnetic resonance: normal values.

AIMS: Myocardial deformation is a key to clinical decision-making. Feature-tracking cardiovascular magnetic resonance (FT-CMR) provides quantification of motion and strain using standard steady-state in free-precession (SSFP) imaging, which is part of a routine CMR left ventricular (LV) study protocol. An accepted definition of a normal range is essential if this technique is to enter the clinical arena. METHODS AND RESULTS: One hundred healthy individuals, with 10 men and women in each of 5 age deciles from 20 to 70 years, without a history of cardiovascular disease, diabetes, renal impairment, or family history of cardiovascular disease, and with a normal stress echocardiogram, underwent FT-CMR assessment of LV myocardial strain and strain rate using SSFP cines.Peak systolic longitudinal strain (Ell) was -21.3 ± 4.8%, peak systolic circumferential strain (Ecc) was -26.1 ± 3.8%, and peak systolic radial strain (Err) was 39.8 ± 8.3%. On Bland-Altman analyses, peak systolic Ecc had the best inter-observer agreement (bias 0.63 ± 1.29% and 95% CI -1.90 to 3.16) and peak systolic Err the least inter-observer agreement (bias 0.13 ± 6.41 and 95% CI -12.44 to 12.71). There was an increase in the magnitude of peak systolic Ecc with advancing age, which was greatest in subjects over the age of 50 years (R(2) = 0.11, P = 0.003). There were significant gender differences (P < 0.001) in peak systolic Ell, with a greater magnitude of deformation in females (-22.7%) than in males (-19.3%). CONCLUSION: Normal values for myocardial strain measurements using FT-CMR are provided. All circumferential and longitudinal based variables had excellent intra- and inter-observer variability.

Inflammation, endothelial dysfunction, and platelet activation in patients with chronic kidney disease: the chronic renal impairment in Birmingham (CRIB) study.

BACKGROUND: Studies in the general population suggest that low-grade inflammation, endothelial dysfunction, and platelet activation are associated with an increased risk of cardiovascular events. METHODS: Markers of inflammation, endothelial dysfunction, and platelet activation were measured in 334 patients with chronic kidney disease (serum creatinine >1.47 mg/dL [>130 micromol/L] at screening) and compared with 2 age- and sex-matched control groups, 1 comprising 92 patients with coronary artery disease and the other comprising 96 apparently healthy individuals with no history of cardiovascular or kidney disease. RESULTS: There was evidence of low-grade inflammation in the chronic renal impairment group compared with healthy controls, with higher concentrations of C-reactive protein (3.70 versus 2.18 mg/L, P < 0.01) and fibrinogen (3.48 versus 2.67 g/L, P < 0.001) and lower serum albumin concentration (41.8 versus 44.0 g/dL [418 versus 440 g/L], P < 0.001). More severe renal impairment was associated with a trend towards higher fibrinogen and lower albumin concentrations (both P < 0.001), although there was no association with higher C-reactive protein level. As compared to healthy controls, plasma von Willebrand factor (142 versus 108 IU/dL, P < 0.001) and soluble P-selectin concentrations (57.0 versus 43.3 ng/mL, P < 0.001) were also higher in the chronic renal impairment group. More severe renal impairment was associated with a trend towards higher levels of von Willebrand factor (P < 0.001) and of soluble P selectin (P < 0.05). CONCLUSION: This cross-sectional analysis demonstrates that chronic kidney disease is associated with low-grade inflammation, endothelial dysfunction, and platelet activation, even among patients with moderate renal impairment.

Cardiovascular risk factors in predialysis patients: baseline data from the Chronic Renal Impairment in Birmingham (CRIB) study.

BACKGROUND: Patients with end-stage kidney failure have a greatly increased risk of developing premature cardiac and vascular disease. However, little is known about the evolution of cardiovascular diseases in individuals with less severely impaired kidney function. METHODS: The prevalence of cardiovascular diseases and of suspected cardiovascular risk factors was studied in a group of 369 individuals (median age, 63 years, 67% male) with various degrees of impaired kidney function (calculated creatinine clearances 6 to 105 mL/min), in 103 patients with angiographically proven coronary artery disease, and in 103 apparently healthy individuals. These patients are being followed prospectively. RESULTS: Of those patients with kidney disease, 34% had a history of vascular disease and 21% had left ventricular hypertrophy on electrocardiogram at baseline. Traditional risk factors were prevalent, with a history of hypertension in 76% of kidney disease patients, diabetes in 15%, and dyslipidemia with reduced low-density lipoprotein (LDL) cholesterol, elevated serum triglycerides, and decreased high-density lipoprotein (HDL) levels. Other possible cardiovascular risk factors include elevated concentrations of plasma homocysteine, as well as low serum albumin and hemoglobin levels. Patients with more severely impaired renal function had lower diastolic blood pressures, lower LDL and HDL cholesterol levels, were more anemic, and had higher plasma homocysteine concentrations. CONCLUSIONS: Vascular disease and left ventricular hypertrophy are prevalent among patients with chronic kidney disease not requiring dialysis. In addition to traditional risk factors, other features of the uremic syndrome such as anemia, hyperhomocysteinemia, and inflammation (suggested by hypoalbuminemia) may contribute.

Mortality in South Asians and Caucasians after percutaneous coronary intervention in the United Kingdom: an observational cohort study of 279,256 patients from the BCIS (British Cardiovascular Intervention Society) National Database.

OBJECTIVES: The purpose of this study was to compare baseline characteristics and medium-term prognosis in South Asian and Caucasian patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: It is unclear whether South Asians undergoing PCI have worse outcomes than Caucasians. METHODS: We performed a retrospective analysis of 279,256 patients undergoing PCI from 2004 to 2011 from the British Cardiovascular Intervention Society national database, of whom 259,318 (92.9%) were Caucasian and 19,938 (7.1%) were South Asian (South Asian includes patients of Pakistani, Indian, Bangladeshi, or Sri Lankan ethnic origin). The main outcome measures were in-hospital major adverse cardiac and cerebrovascular events and all-cause mortality during a median follow-up of 2.8 years (interquartile range: 1.5 to 4.5 years). RESULTS: South Asians were younger (59.69 ± 0.27 years vs. 64.69 ± 0.13 years, p > 0.0001); more burdened by cardiovascular risk factors, particularly diabetes mellitus (42.1 ± 1.2% vs. 15.4 ± 0.4%, p > 0.0001); and more likely to have multivessel coronary disease than Caucasians. In-hospital rates of major adverse cardiac and cerebrovascular events were similar for South Asians and Caucasians (3.5% vs. 2.8%, p = 0.40). Unadjusted Kaplan-Meier estimates of all-cause mortality showed better survival for South Asians compared with Caucasians, after PCI for either acute myocardial infarction or angina. Age-adjusted analysis revealed increased mortality (hazard ratio: 1.24; 95% confidence interval: 1.18 to 1.30), but after adjustment for the substantial variation in baseline risk factors including diabetes, there was no significant difference between South Asians and Caucasians (hazard ratio: 0.99; 95% confidence interval: 0.94 to 1.05). CONCLUSIONS: In this large, contemporary cohort of patients treated by PCI, South Asians were younger but had more extensive disease and major risk factors, particularly diabetes. However, after correcting for these differences, in-hospital and medium-term mortality of South Asians was no worse than that of Caucasians. This suggests that in South Asians, the high prevalence of diabetes exerts an adverse influence on mortality, but ethnicity itself is not an independent predictor of outcome.

Feature-tracking cardiovascular magnetic resonance as a novel technique for the assessment of mechanical dyssynchrony.

BACKGROUND: Myocardial tagging using cardiovascular magnetic resonance (CMR) is the gold-standard for the assessment of myocardial mechanics. Feature-tracking cardiovascular magnetic resonance (FT-CMR) has been validated against myocardial tagging. We explore the potential of FT-CMR in the assessment of mechanical dyssynchrony, with reference to patients with cardiomyopathy and healthy controls. METHODS: Healthy controls (n=55, age: 42.9 ± 13 yrs, LVEF: 70 ± 5%, QRS: 88 ± 9 ms) and patients with cardiomyopathy (n=108, age: 64.7 ± 12 yrs, LVEF: 29 ± 6%, QRS: 147 ± 29 ms) underwent FT-CMR for the assessment of the circumferential (CURE) and radial (RURE) uniformity ratio estimate based on myocardial strain (both CURE and RURE: 0 to 1; 1=perfect synchrony) RESULTS: CURE (0.79 ± 0.14 vs. 0.97 ± 0.02) and RURE (0.71 ± 0.14 vs. 0.91 ± 0.04) were lower in patients with cardiomyopathy than in healthy controls (both p<0.0001). CURE (area under the receiver-operator characteristic curve [AUC]: 0.96), RURE (AUC: 0.96) and an average of these (CURE:RUREAVG, AUC: 0.98) had an excellent ability to discriminate between patients with cardiomyopathy and controls (sensitivity 90%; specificity 98% at a cut-off of 0.89). The time taken for semi-automatically tracking myocardial borders was 5.9 ± 1.4 min. CONCLUSION: Dyssynchrony measures derived from FT-CMR, such as CURE and RURE, provide almost absolute discrimination between patients with cardiomyopathy and healthy controls. The rapid acquisition of these measures, which does not require specialized CMR sequences, has potential for the assessment of mechanical dyssynchrony in clinical practice.

Serum free light chains and the risk of ESRD and death in CKD.

BACKGROUND AND OBJECTIVES: Associations between inflammation and ESRD and death in chronic kidney disease are well established. However, the potential role of the adaptive immune system is uncertain. We aimed to prospectively study the relevance of the adaptive immune system to ESRD and mortality by measuring monoclonal and polyclonal excesses of highly sensitive serum free light chains (sFLCs). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Three hundred sixty-four patients selected from a nephrology outpatient clinic had kappa and lambda sFLCs concentrations and serum immunofixation electrophoresis measured. Cox regression was used to assess the relevance of monoclonal and polyclonal excess of sFLCs to the incidence of ESRD and death (mean follow-up for death 6.0 years). RESULTS: After adjustment for baseline eGFR, there was no significant association between monoclonal excess of sFLCs and risk of ESRD or mortality. Baseline log κ and log λ concentrations were positively associated with ESRD risk, but these associations seemed to be due to correlations with eGFR (per 1 SD higher concentration: adjusted hazard ratio 1.05 [95% confidence interval 0.88 to 1.26] and 0.99 [0.83 to 1.19], respectively). For mortality, after adjustment for eGFR plus markers of cardiac damage, there was weak evidence of an association with λ, but not κ, sFLC concentration (fully adjusted hazard ratio 1.33 [95% confidence interval 1.05 to 1.67] per 1 SD higher concentration). CONCLUSIONS: Associations between monoclonal and polyclonal excess of sFLCs and risk of ESRD are explained by the correlation between these measures and renal function. We found only weak evidence of an association between polyclonal excess of λ sFLC concentration and mortality.

Don't rule out retroperitoneal bleeding just because the angiogram was done from the radial artery.

The use of radial artery for vascular access for cardiac catheterization and intervention has gained increasing acceptance over the last few years as result of the lower risk of vascular complications compared to use of the femoral artery. The strong evidence showing that major bleeding (commonly access site related) is an independent predictor of mortality in acute coronary syndrome patients undergoing intervention has only accelerated this change. This case highlights that although the risk of access site complications is reduced with the radial approach there remains a risk of spontaneous bleeding elsewhere due to the use of multiple potent antiplatelet and anticoagulant therapy in the treatment of acute coronary syndromes. Early recognition of bleeding is of the utmost importance as delay increases the likelihood complications of bleeding including death.

Subclinical abnormalities of left ventricular myocardial deformation in early-stage chronic kidney disease: the precursor of uremic cardiomyopathy?

BACKGROUND: Abnormal left ventricular (LV) deformation is an independent predictor of poor cardiovascular outcome in end-stage renal disease. Studies in early-stage chronic kidney disease (CKD) have not been performed despite the known graded inverse relationship between glomerular filtration rate and adverse cardiovascular events. METHODS: Forty patients with CKD stage 2 or 3 and no history of cardiovascular disease or diabetes and 30 healthy controls underwent Doppler myocardial imaging for longitudinal deformation (strain/strain rate). RESULTS: There were no differences in LV ejection fraction or systolic tissue Doppler velocities between patients with CKD and controls. In CKD, mean global strain (-15% +/- 4% vs -17% +/- 3%, P <.01) and mean global strain rate were reduced compared with controls (-0.88 +/- 0.16 vs -1.06 +/- 0.31, P <.05). Peak systolic strain was reduced in the basal lateral (-13.9% +/- 0.9% vs -17.9% +/- 1.02%, P <.01), basal septal (-17.1% +/- 0.8% vs -19.4% +/- 0.77%, P <.05), and mid-septal (-16.4% +/- 0.78% vs -18.9% +/- 0.88%, P <.05) walls with more basal postsystolic shortening (P <.01). Peak systolic strain rate was reduced in the basal lateral, mid-lateral, and mid-septal segments (P <.05). CONCLUSION: Conventional measures of systolic function are preserved in early-stage CKD, but systolic deformation is abnormal, consistent with an adverse cardiovascular prognosis.

Improved myocardial protection during coronary artery surgery with glucose-insulin-potassium: a randomized controlled trial.

OBJECTIVE: We sought to assess the role of glucose-insulin-potassium in providing myocardial protection in nondiabetic patients undergoing coronary artery surgery with cardiopulmonary bypass. METHODS: A prospective, randomized, double-blind, placebo-controlled trial was conducted at a single-center university hospital performing adult cardiac surgery. Two hundred eighty nondiabetic adult patients undergoing first-time elective or urgent isolated multivessel coronary artery bypass grafting were prospectively randomized to receive glucose-insulin-potassium infusion or placebo (dextrose 5%) before, during, and for 6 hours after surgical intervention. Anesthetic, cardiopulmonary bypass, myocardial protection, and surgical techniques were standardized. The primary end point was postreperfusion cardiac index. Secondary end points were systemic vascular resistance index, the incidence of low cardiac output episodes, inotrope and vasoconstrictor use, and biochemical-electrocardiographic evidence of myocardial injury. The incidence of dysrhythmias and infections requiring treatment was recorded prospectively. RESULTS: The glucose-insulin-potassium group experienced higher cardiac indices (P < .001) throughout infusion and reduced vascular resistance (P < .001). The incidence of low cardiac output episodes was 15.9% (22/138) in the glucose-insulin-potassium group and 27.5% (39/142) in the placebo group (P = .021). Inotropes were required in 18.8% (26/138) of the glucose-insulin-potassium group and 40.8% (58/142) of the placebo group (P < .001). Fewer patients in the glucose-insulin-potassium group (12.3% [16/133]) versus those in the placebo group (23.4% [32/137]) had significant myocardial injury (P = .017). Noncardiac morbidity was not different. CONCLUSION: Glucose-insulin-potassium therapy improves early postoperative cardiovascular performance, reduces inotrope requirement, and might reduce myocardial injury. These potential benefits are not at the expense of increased noncardiac morbidity.

Mortality, cardiac vagal control and physical training--what's the link?

There is little doubt that regular exercise results in increases in life expectancy and protects against adverse cardiac events in both healthy subjects and patients with cardiovascular disease. The mechanism of action of physical training remains unclear but a variety of evidence points towards an enhancement in cardiac vagal activity protecting against lethal arrhythmias. Just how physical training increases cardiac vagal activity is an area that is ill understood but plausible mechanisms include mediation via angiotensin II or NO. Further research is needed in this area. Exercise training is demanding and difficult, particularly for patients with cardiac disease. If the mechanism of increase in cardiac vagal activity with training can be determined it may be possible to use pharmacological approaches to mimic the effects of exercise with potentially beneficial effects.

The angiotensin-converting enzyme gene I/D polymorphism and heart rate variability following acute myocardial infarction.

AIMS: Heart rate variability (HRV) is a measure of cardiac autonomic control and is therefore subject to regulation by the renin-angiotensin system. The primary objective of this study was to determine the effect of an insertion/deletion polymorphism within the angiotensin-converting enzyme (ACE) gene on HRV in the early stages after a myocardial infarction at a time when cardiac autonomic control is deranged. The secondary objective was to determine whether this polymorphism affected the HRV response to inhibition of ACE. MAJOR FINDINGS: 149 Caucasian subjects were studied 25 +/- 16 h following MI using time and frequency domain measures of HRV derived from two 5-minute ECG recordings. Recordings were repeated at 182 +/- 65 h following MI, when subjects had been stabilised on ramipril 2.5 mg bd. The study included 46 subjects with the DD genotype, 69 with the ID genotype, and 34 with the II genotype. No effect of the I/D polymorphism on short-term recordings of HRV was found. There was no difference in HRV response to the introduction of ramipril according to the genotypes. PRINCIPAL CONCLUSIONS: The I/D polymorphism within the ACE gene does not influence HRV after MI or the HRV response to ACE inhibitor therapy with ramipril. These findings may reflect the relative lack of importance of the I/D polymorphism and ACE activity in determining plasma and tissue angiotensin II concentration after a major stimulus to the renin-angiotensin system as occurs after myocardial infarction.