The Scottish-Finnish-Swedish PARTNER study of taprostene versus placebo treatment in patients with critical limb ischemia.

AIM: Atherosclerotic peripheral arterial disease is a major health problem in the western world, often manifested as intermittent claudication, affecting 10-20% males above 60 years. Ischemic complications can lead to rest pain, ulceration and gangrene. The treatment of choice for critical limb ischemia (CLI) is vascular reconstruction or endovascular interventions. Medical management with vasodilator antiplatelet prostaglandins, could be considered in patients unsuitable for surgery. Long term follow-up on previous prostaglandin studies has been insufficient to evaluate amputation rates. Hence this study evaluated safety and longer term efficacy of taprostene sodium, a prostacyclin (PGI2) analogue in CLI. The aim of this study was to determine whether Taprostene sodium, a PGI2 analogue, was a safe and effective treatment for CLI. METHODS: This paper reports the data from the Scottish-Finnish-Swedish PARTNER Study Group which consisted of a double-blind placebo controlled multi-centre study evaluating Taprostene compared to placebo. The primary endpoints were pain relief and early ulcer healing response at the end of the four week infusion phase and amputation at six months follow-up. The patients were randomly allocated to receive taprostene or placebo in a two to one randomization of active versus placebo. A total of 111 patients with CLI were recruited. Taprostene was given twice a day over two 2 hour periods for four weeks. The early response was evaluated at the end of the four week infusion phase. In patients with rest pain without ulceration, a positive response was complete pain relief without any requirement for analgesic therapy. However in patients with ulceration, a positive response was defined as a decrease in the ulcer size by >30%. Amputation scores were compared at the end of the 6 months follow-up period for all participants. RESULTS: Seventy-four patients received taprostene and 37 placebo. Overall, 61 male patients were enrolled in the study along with 50 females with 11% more women in the taprostene (active) group. For both patients with and without ulcers there was no statistically significant difference noted in the early response between those receiving taprostene and those receiving placebo infusion. The percentage of patients without any amputations was 43% in the taprostene group compared to 38% in the control group at the end of six months; however, these results were not statistically significant. CONCLUSION: Although a reasonable number of patients enrolled in the study it has not been possible to demonstrate any statistically significant benefit of taprostene over placebo. This may be due to more patients with risk factors for peripheral artery disease (PAD) such as hypertension, diabetes mellitus and cigarette smoking in the actively treated group and also due the increased number of women in the active group who are known to generally respond less favourably to antiplatelet agents.

Renal function assessed by two different formulas and incidence of myocardial infarction and death in middle-aged men and women.

BACKGROUND: Chronic kidney disease predicts mortality in the general population, but less is known about the association with incidence of first myocardial infarction. We evaluated glomerular filtration rates (GFR) estimated by the Modification of Diet in Renal Disease study (GFR-MDRD) equation and the Mayo formula (GFR-Mayo) as predictors of myocardial infarction and death. METHODS: In 571 353 Swedish men and women, undergoing health controls, with mean age 45 years, and no previous myocardial infarction, hazard ratios were calculated to assess the association between renal function and incidence of myocardial infarction and all-cause mortality, respectively. Glomerular filtration rate 60-90, 30-60 and <30 mL per minute per 1.73 m(2), was defined as mildly, moderately and severely decreased GFR, respectively. RESULTS: There were 19 510 myocardial infarctions and 56 367 deaths during 11.6 years of follow-up. Hazard ratios (and 95% confidence intervals) for myocardial infarction, using GFR-Mayo were 1.11 (1.06-1.16) for mildly, 1.32 (1.18-1.48) for moderately and 2.54 (1.90-3.40) for severely decreased GFR. The corresponding figures for GFR-MDRD were 1.01 (0.96-1.05), 1.23 (1.14-1.32) and 2.49 (1.85-3.35). Mortality was increased at all levels of reduced GFR-Mayo and at moderately or severely decreased GFR-MDRD. CONCLUSIONS: Already mildly decreased GFR increase the risk of myocardial infarction and death in the general population. The association with adverse outcomes is stronger when GFR-Mayo rather than GFR-MDRD is used to assess renal function.

Influence of statin treatment on platelet inhibition by clopidogrel - a randomized comparison of rosuvastatin, atorvastatin and simvastatin co-treatment.

OBJECTIVES: Possible interactions between clopidogrel and atorvastatin, simvastatin or rosuvastatin (a 'non-CYP3A4' metabolized statin) were investigated in a randomized prospective study using sensitive and specific ex vivo platelet function tests. METHODS: Patients with coronary artery disease participating in a double-blind study comparing lipid-lowering effects of atorvastatin (20-80 mg OD; n = 22) and rosuvastatin (10-40 mg OD; n = 24) were studied before and after 2 weeks treatment with clopidogrel 75 mg OD after completed statin dose titration. In addition, 23 patients were randomized to open-label simvastatin 40 mg OD. RESULTS: Clopidogrel inhibited 10 mumol L(-1) ADP-induced platelet aggregation by 40 +/- 27%, 57 +/- 28% and 51 +/- 29%, respectively, in patients on rosuvastatin, atorvastatin and simvastatin treatment. The other platelet tests yielded similar results. No dose-dependent effects of rosuvastatin or atorvastatin co-treatment on clopidogrel efficacy were observed. CONCLUSIONS: Treatment with CYP3A4 metabolized statins, atorvastatin or simvastatin, did not attenuate the platelet inhibitory effect of clopidogrel maintenance treatment compared with the non-CYP3A4 metabolized, rosuvastatin.

Cystatin C--a marker of peripheral atherosclerotic disease?

UNLABELLED: It has been suggested that Cystatin C, besides its function as a marker of glomerular filtration, could be an independent marker of cardiovascular disease. However, studies on this topic are few and results have been indecisive. Our aim was to further investigate the subject of Cystatin C as an independent marker of peripheral atherosclerotic disease. METHOD: Blood samples were analysed for serum Cystatin C, IL6, CRP and creatinine in 103 males with peripheral arterial disease (PAD) and 96 controls matched for age and sex. Creatinine clearance (CCr) was calculated according to Cockcroft's formula and estimated glomerular filtration rate (eGFR) was calculated according to MDRD formula. RESULTS: Cystatin C-concentration was higher in PAD-patients compared to controls; 1.09+/-0.40 vs. 0.95+/-0.17 mg/L (p<0.01). There was no difference in CCr; 81+/-27 vs. 82+/-22 mL/min or eGFR; 76+/-21 vs. 79+/-14 mL/min. Cystatin C correlated to CCr, logIL-6 and logCRP in both patients (r=-0.60, p<0.001), (r=0.35, p<0.001) and (r=0.30, p<0.01) and controls (-0.44, p<0.001), (0.38, p<0.001) and (r=0.32, p<0.01), respectively. In an analysis of covariance, corrected for difference in eGFR, Cystatin C remained higher in PAD-patients compared to controls; 1.09 (C.I. 1.04-1.14) vs. 0.96 (C.I. 0.90-1.01). CONCLUSION: Cystatin C-concentration, corrected for differences in eGFR, IL-6 and CRP values, is higher in PAD-patients compared to controls. Our finding suggests that Cystatin C may be an independent marker of atherosclerotic disease apart from its relation to kidney function.

Prevalence and prognostic implications of electrocardiographic left ventricular hypertrophy in heart failure: evidence from the CHARM programme.

BACKGROUND: Electrocardiographic left ventricular hypertrophy (ECG LVH) is a powerful independent predictor of cardiovascular morbidity and mortality in hypertension. OBJECTIVE: To determine the contemporary prevalence and prognostic implications of ECG LVH in a broad spectrum of patients with heart failure with and without reduced left ventricular ejection fraction (LVEF). METHODS AND OUTCOME: The Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme randomised 7599 patients with symptomatic heart failure to receive candesartan or placebo. The primary outcome comprised cardiovascular death or hospital admission for worsening heart failure. The relative risk (RR) conveyed by ECG LVH compared with a normal ECG was examined in a Cox model, adjusting for as many as 31 covariates of prognostic importance. RESULTS: The prevalence of ECG LVH was similar in all three CHARM trials (Alternative, 15.4%; Added, 17.1%; Preserved, 14.7%; Overall, 15.7%) despite a more frequent history of hypertension in CHARM-Preserved. ECG LVH was an independent predictor of worse prognosis in CHARM-Overall. RR for the primary outcome was 1.27 (95% confidence interval (CI) 1.04 to 1.55, p = 0.018). The risk of secondary end points was also increased: cardiovascular death, 1.50 (95% CI 1.13 to 1.99, p = 0.005); hospitalisation due to heart failure, 1.19 (95% CI 0.94 to 1.50, p = 0.148); and composite major cardiovascular events, 1.35 (95% CI 1.12 to 1.62, p = 0.002). CONCLUSION: ECG LVH is similarly prevalent in patients with symptomatic heart failure regardless of LVEF. The simple clinical finding of ECG LVH was an independent predictor of a worse clinical outcome in a broad spectrum of patients with heart failure receiving extensive contemporary treatment. Candesartan had similar benefits in patients with and without ECG LVH.

Office blood pressure underestimates ambulatory blood pressure in peripheral arterial disease in comparison to healthy controls.

Patients with peripheral arterial disease (PAD) constitute a subgroup of high-risk hypertensives, but controlled studies on 24-h blood pressure (BP) and diurnal variation of BP are lacking. This study was performed in order to test the hypothesis that office BP (OBP) may underestimate 24-h BP in PAD patients in comparison to a matched control group. In all, 98 male patients (mean age 68 years) with a history of intermittent claudication and an ankle/brachial index less than 0.9, and 94 controls matched for age but without PAD or ischaemic heart disease performed 24-h recordings of ambulatory BP. A total of 59 patients had a history of hypertension and 69 were on treatment with BP-lowering drugs as compared to 17 and 23 of the control subjects, respectively. Office as well as 24-h systolic BP (SBP) were higher in patients as compared to controls (151 +/- 22 vs 140 +/- 20 mmHg, P < 0.001 and 142 +/- 14 vs 133 +/- 15 mmHg, P < 0.001, respectively), but did not differ with regard to diastolic BP. In an analysis of covariance with the continuous factors age, office SBP and the categorical factor antihypertensive treatment, 24-h SBP was higher in PAD patients compared to controls (P < 0.05). The difference between office and night SBP was lower in PAD patients with antihypertensive treatment compared to controls (P = 0.01). In conclusion, Male patients with PAD had higher systolic but not diastolic BP than age-matched control subjects. In PAD patients, 24-h SBP was higher than expected from OBP compared to controls. Night SBP was higher only in patients with antihypertensive treatment. In PAD patients, especially when on antihypertensive treatment, the severity of hypertension may be underestimated when based on OBP only.

Impact of ramipril in patients with evidence of clinical or subclinical peripheral arterial disease.

AIMS: The aim of this study was to assess the prognostic importance of peripheral arterial disease (PAD) as evaluated by ankle blood pressure index (ABI), and the impact of ramipril on the prevention of major cardiovascular events in PAD patients included in the Heart Outcomes Prevention Evaluation (HOPE) study. METHODS AND RESULTS: Patients were randomized to treatment with ramipril or placebo and followed for 4.5 years. Ankle brachial blood pressure index was measured, mainly by digital palpation of the foot pulse, at baseline in 8986 patients. The ABI was subnormal (< or =0.9) in 3099 patients and normal in 5887 patients. A low ABI was a strong predictor of morbidity and mortality during the follow-up even in patients with no clinical symptoms of PAD (n=6769). This was so for the primary outcome of the study; ABI>0.9:13.1%, 0.6-0.9: 18.2% and <0.6: 18.0% (P<0.0001) and for mortality from all causes: in those with a normal ABI it was 8.5%, in those with ABI >0.6-0.9, 12.4% and 14.2% in those with an ABI lower than 0.6 (P<0.0001). Ramipril reduced the risk of clinical outcomes in those with a clinical history of PAD as well as in the patients with subclinical PAD. CONCLUSIONS: The ABI even if measured simply by palpation of the foot arteries is a strong predictor for future cardiovascular events and for all-cause mortality. Ramipril prevented major cardiovascular events in patients with clinical as well as subclinical PAD.

Clinical features and contemporary management of patients with low and preserved ejection fraction heart failure: baseline characteristics of patients in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme.

AIMS: To describe the clinical characteristics and contemporary treatment of a broad spectrum of patients with chronic heart failure (CHF) randomised in the Candesartan in Heart failure-Assessment of Reduction in Mortality and morbidity (CHARM) programme, consisting of three component studies comparing placebo to candesartan. METHODS AND RESULTS: CHARM Alternative, CHARM Added and CHARM Preserved enrolled 2028 low left ventricular ejection fraction (LVEF) ACE inhibitor intolerant patients, 2548 low LVEF ACE inhibitor treated patients and 3025 preserved LVEF patients, respectively. Patients in CHARM Preserved were more often female. The proportion of women in CHARM Preserved was 40% compared to 32% in CHARM Alternative and 21% in CHARM Added. Patients in CHARM Preserved were also more often hypertensive than in the other two trials (64% vs. 50% and 48%, respectively). Symptoms and signs (with the exception of a third heart sound) were similar in all three patient groups. Beta-blockers were used in over half of patients in all three groups. Digoxin and spironolactone were used less frequently and calcium antagonists more frequently in CHARM Preserved. Spironolactone was used most frequently in CHARM Alternative, i.e. in ACE inhibitor intolerant patients. CONCLUSIONS: The CHARM Programme provides the largest and most detailed comparison to date of patients low- and preserved-LVEF CHF. It also describes the causes of ACE-inhibitor intolerance in a large cohort of patients and the other treatment which these patients receive.

The cost-effectiveness of ramipril in the treatment of patients at high risk of cardiovascular events: a Swedish sub-study to the HOPE study.

OBJECTIVE: To evaluate if long-term treatment with ramipril is cost-effective in patients at high risk of cardiovascular events. DESIGN: Randomized double-blind and placebo controlled. Information was gathered prospectively for a number of direct medical, direct nonmedical and indirect costs. SETTING AND SUBJECT: This is a sub-study to the Heart Outcomes Prevention Evaluation (HOPE) study performed in Swedish patients. All Swedish centres (19; n= 554) were invited to take part and 18 centres agreed to do so (n=537). The patients were managed in a specialist setting with a mean follow-up period of 4.5 years. Main outcome measures. The number of life-years saved was derived from the global HOPE study (n=9297) and subsequently the estimated life expectancy of those who completed the clinical study alive was added to the calculation. Direct medical costs related to cardiovascular disease only were considered in the primary analysis, whilst all kinds of costs and costs for all kinds of diseases were included in subsequent analyses. The cost of added years of life, according to the future cost method, was included in sensitivity analyses. RESULTS: The cost per life-year gained was SEK 16 600 (Euro 1940) when direct medical costs for cardiovascular reasons only were considered and SEK 45 400 (Euro 5300) when direct medical costs for all diseases were considered. The corresponding costs when direct nonmedical and indirect cost were added to the estimate were SEK 16 100 (Euro 1880) and SEK 54 600 (Euro 6380), respectively. When the future cost method was applied, the cost per life-year gained was SEK 208 300 (Euro 24 300). CONCLUSION: Ramipril is highly cost-effective in the treatment of patients at high risk of cardiovascular events.

Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy.

In the HOPE-trial, the ACE inhibitor ramipril significantly reduced cardiovascular morbidity and mortality in patients at high risk for cardiovascular events. The benefit could only partly be attributed to the modest mean reduction of office blood pressure (OBP) during the study period (3/2 mm Hg). However, because according to the HOPE protocol ramipril was given once daily at bedtime and blood pressure was measured during the day, the 24-hour reduction of blood pressure may be underestimated based on OBP. Thirty-eight patients with peripheral arterial disease enrolled in the HOPE study underwent 24-hour ambulatory blood pressure (ABP) measurement before randomization and after 1 year. OBP was measured in the sitting position immediately before fitting the ABP measuring equipment to the patients. Ramipril did not significantly reduce OBP (8/2 mm Hg, P=NS) or day ABP (6/2 mm Hg, P=NS) after 1 year. Twenty-four-hour ABP was significantly reduced (10/4 mm Hg, P=0.03), mainly because of a more pronounced blood pressure lowering effect during nighttime (17/8 mm Hg, P<0.001). The night/day ratio was also significantly lowered in the ramipril group. ABP shows greater falls, especially at night, than OBP during treatment with ramipril given once daily at bedtime. Although, OBP is the correct comparator when comparing with previous large intervention trials and epidemiological studies, the effects on cardiovascular morbidity and mortality seen with ramipril in the HOPE study may, to a larger extent than previously ascribed, relate to effects on blood pressure patterns over the 24-hour period.

Pharmacoeconomic impact of HOPE.

The HOPE (Heart Outcomes and Prevention Evaluation) study has demonstrated a clear and beneficial effect of ramipril on cardiovascular events and disease progression. The cost-effectiveness of treatment with ramipril remains an important question that is being addressed by analysis of data from the main HOPE study and from a Swedish substudy. Data from the main HOPE study indicate that hospital costs per patient were reduced in the ramipril group compared with the placebo group. The net effect indicates that ramipril is cost neutral or could even be cost saving in US non-Medicare patients. In the Swedish health economic substudy, a separate protocol and separate case record forms were utilised to generate more specific data from the 537 Swedish patients taking part in HOPE. In this analysis, costs and effects associated with each treatment group were assessed and incremental cost-effectiveness ratios were calculated. The primary analysis was cost per life year gained which amounted to 29,000 Swedish Kroner. In a world with a growing prevalence of cardiovascular disease and with additional constraints on healthcare expenditure, analysis of the cost-effectiveness of preventive and curative medications is increasingly important. In this context, the early observations on the cost-effectiveness of ramipril appear very hopeful.

What is the relevance of the HOPE study in general practice?

The unique findings from the HOPE (Heart Outcomes Prevention Evaluation) study strongly support extending the use of the angiotensin-converting enzyme (ACE) inhibitor ramipril as a preventive agent for patients at high risk of cardiovascular events with normal left ventricular function. In addition, ramipril provides significant benefit in diabetic patients. These findings will impact on how ramipril is used in primary care, where ACE inhibitors are currently underprescribed. Patients reflecting the inclusion criteria of the HOPE study should be considered as suitable candidates for long-term ramipril therapy as an addition to their existing drug regimen. Screening should include control of kidney function (by serum creatinine), particularly within the first two weeks of treatment, in addition to regular monitoring of serum potassium. However, the HOPE study shows that ramipril is well tolerated at high doses and over a long treatment period. The effectiveness of therapy should also be regularly reviewed and dose adjustments made where necessary. If concern remains, referral to a specialist--a cardiologist or a diabetologist--may ultimately be necessary.

Regression of left ventricular mass with captopril and metoprolol, and the effects on glucose and lipid metabolism.

OBJECTIVE: Angiotensin II and insulin have been suggested to promote the development of hypertensive left ventricular (LV) hypertrophy. We compared the effects of captopril and metoprolol on the regression of LV mass and the relation to insulin sensitivity. DESIGN: 51 previously untreated non-diabetic hypertensive patients (mean age 51 +/- 8 years, body mass index, BMI 25.9 +/- 3.2 kg/m2, office blood pressure, 158/102 mmHg) were randomized to captopril or metoprolol; a low-dose diuretic and/or a calcium cannel antagonist were added, if needed. INTERVENTIONS: LV mass index (LVMI; by echocardiography) and 24-h ambulatory blood pressure were examined at baseline, 6 and 12 months. At baseline and 12 months, insulin sensitivity index (MI) was calculated by a hyperinsulinemic-euglycemic insulin clamp technique. RESULTS: Blood pressures were reduced similarly in both groups. LVMI (115 +/- 21 g/m2 at baseline) was reduced in both groups (p < 0.01), but more with captopril than with metoprolol (e.g. -16 vs -7 g/m2, i.e. -13 vs -6%, at 12 months, p < 0.01). MI decreased by 6% with captopril (p = 0.05) and by 23% with metoprolol (p < 0.01), with no difference between the groups. Changes in LVMI were not related to changes in MI in the two groups, or when all patients were analyzed together. High-density lipoprotein (HDL)-cholesterol decreased (p < 0.05) by both drugs, with small effects on low-density lipoprotein (LDL), and triglycerides increased by 30% with metoprolol (p < 0.01). CONCLUSION: Blockade of the renin-angiotensin-aldosterone system has a role beyond that of blood pressure reduction in the regression of LV mass. There was no relationship between regression of LV mass and improvement in insulin sensitivity. We could not confirm a beneficial effect of ACE inhibition on insulin sensitivity. Thus, our results do not support the importance of insulin in the control of LV geometry.

Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial. ASCOT investigators.

OBJECTIVE: To test the primary hypothesis that a newer antihypertensive treatment regimen (calcium channel blocker +/- an angiotensin converting enzyme inhibitor) is more effective than an older regimen (beta-blocker +/- a diuretic) in the primary prevention of coronary heart disease (CHD). To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol < or = 6.5 mmol/l. DESIGN: Prospective, randomized, open, blinded endpoint trial with a double-blinded 2 x 2 factorial component. SETTING: Patients were recruited mainly from general practices. PATIENTS: Men and women aged 40-79 were eligible if their blood pressure was > or = 160 mmHg systolic or > or = 100 mmHg diastolic (untreated) or > or = 140 mmHg systolic or > or = 90 mmHg diastolic (treated) at randomization. INTERVENTIONS: Patients received either amlodipine (5/ 10 mg) +/- perindopril (4/8 mg) or atenolol (50/ 100 mg) +/- bendroflumethiazide (1.25/2.5 mg) +K+ with further therapy as required to reach a blood pressure of < or = 140 mmHg systolic and 90 mmHg diastolic. Patients with a total cholesterol of < or = 6.5 mmol/l were further randomized to receive either atorvastatin 10 mg or placebo daily. MAIN OUTCOME MEASURE: Non-fatal myocardial infarction (MI) and fatal coronary heart disease (CHD). RESULTS: 19 342 men and women were initially randomized, of these 10297 were also randomized into the lipid-lowering limb. All patients had three or more additional cardiovascular risk factors. CONCLUSIONS: The study has 80% power (at the 5% level) to detect a relative difference of 20% in CHD endpoints between the calcium channel blocker-based regimen and the beta-blocker-based regimen. The lipid-lowering limb of the study has 90% power at the 1% level to detect a relative difference of 30% in CHD endpoints between groups.

Factors predicting success rate and recurrence of atrial fibrillation after first electrical cardioversion in patients with persistent atrial fibrillation.

BACKGROUND: The recurrence rate of atrial fibrillation (AF) after elective cardioversion is high. HYPOTHESIS: The study aimed to identify clinical predictors for successful electrical cardioversion and maintenance of sinus rhythm after a first electrical cardioversion in patients with persistent AF without concomitant antiarrhythmic drugs of class I and III. METHODS: Consecutive outpatients (n = 166) with persistent AF for > 1 month, scheduled for elective cardioversion, were prospectively included in the study. A clinical investigation, echocardiographic assay, and Holter electrocardiogram (ECG) before and ECG 4 weeks after cardioversion, were performed in all patients. RESULTS: The mean age of the patients was 68 years (range 45-83) and duration of AF was 5 (1-48) months. Sinus rhythm was established in 124 (75%) patients. In multivariate analysis, only duration of AF < 6 months (p < 0.04, odds ratio [OR] 2.2, 95% confidence interval [CI] 1.1 to 4.7) and patients weight (p < 0.03, OR 2.3, 95% CI 1.1 to 4.8 for weight < 80 kg) were identified as independent predictors of successful cardioversion. At 4 weeks after cardioversion, only 46 (37%) of 124 patients maintained sinus rhythm. Independent factors for maintenance of sinus rhythm, in multivariate analysis, were AF <3 months (p < 0.04, OR 2.5, 95% CI 1.1 to 5.6), treatment with beta blockers (p < 0.00001, OR 7.0, 95% CI 3.0 to 16.3) or verapamil/diltiazem (p < 0.04, OR 3.6, 95% CI 1.1 to 12.1), and right atrial dimension < 37 mm (p < 0.02, OR 5.9, 95% CI 1.4 to 25.4). CONCLUSIONS: In patients with persistent AF, the patient's weight and the duration of AF are independent predictors for a successful cardioversion. Short duration of AF, treatment with beta blockers or verapamil/diltiazem, and right atrial area/dimension are independent predictors for maintenance of sinus rhythm.

Left ventricular mass is not related to insulin sensitivity in never-treated primary hypertension.

OBJECTIVE: Insulin has been suggested to promote myocardial cell growth and the development of left ventricular (LV) hypertrophy. This study examines the possible relationship between LV mass and insulin sensitivity. DESIGN: Previously untreated non-diabetic hypertensive patients. PATIENTS: Fifty-one patients with mean age 51 +/- 8 years, body mass index (BMI) 25.9 +/- 3.2 kg/m2 and blood pressure 158/102 mmHg were included. LV mass was determined by echocardiography. Glucose metabolism was assessed by an euglycemic insulin clamp (40 mU/m2 body surface area/min). RESULTS: Insulin sensitivity index (MI) and insulin clearance were inversely related to LV mass (r = -0.37, P < 0.01 and -0.33, P < 0.05, respectively) and LV mass indexed to height (r = -0.33, P < 0.05 and -0.29, P < 0.05, respectively). C-peptide and fasting insulin were related to LV mass (r = 0.33, P < 0.05 and r = 0.36, P < 0.01, respectively) and LV mass indexed to height (r = 0.30, P < 0.05 and r = 0.34, P < 0.05, respectively). In contrast, when LV mass was indexed by body surface area there was no longer a relation to MI, insulin clearance, C-peptide or fasting insulin. When adjusting for BMI in a multiple regression analysis, MI and LV mass no longer showed a relation. Indeed, MI, insulin clearance, C-peptide and insulin were all strongly related to weight and BMI. CONCLUSION: Insulin sensitivity is related to body size in untreated hypertension. However, insulin sensitivity is not related to LV mass, if adjusting for body size. This does not support a direct growth-promoting effect of insulin on the myocardium. Insulin does not appear to be strongly involved in development of hypertensive LV hypertrophy.

Asymptomatic versus symptomatic persistent atrial fibrillation: clinical and noninvasive characteristics.

OBJECTIVE: This prospective study was designed to investigate the differences between asymptomatic versus symptomatic arrhythmia as well as left ventricular dysfunction in a consecutive population of patients with persistent atrial fibrillation. DESIGN: A total of 282 consecutive outpatients referred with persistent atrial fibrillation formed the study population. A structured medical history was obtained. A two-dimensional transthoracic echocardiography to assess the left ventricular function and a 24-h electrocardiogram (ECG) recording were performed. Irregularity of the heart rhythm was analysed with heart rate variability (HRV) in the time domain as well as maximum and minimum heart rate and the longest pause. SETTING: Three university hospitals. RESULTS: The mean age of the patients was 69 years and the mean duration of atrial fibrillation was 7 months. The prevalence of symptomatic patients was 68%, while 32% had no symptoms from atrial fibrillation, left ventricular dysfunction was observed in 20%. Asymptomatic subjects had more often lone atrial fibrillation than those with symptoms. Valvular heart disease was an independent predictor of symptoms while male gender, ischaemic heart disease and a high heart rate were independent predictors of impaired left ventricular function. CONCLUSION: Valvular heart disease is related to symptoms in persistent atrial fibrillation. Ischaemic heart disease, male gender and a high heart rate are more common in patients with impaired left ventricular function. Compromised left ventricular function does, occur also in asymptomatic subjects underlining the importance of a careful investigation including echocardiography in all subjects with persistent atrial fibrillation.