Myocardial infarction with normal coronary arteries is common and associated with normal findings on cardiovascular magnetic resonance imaging: results from the Stockholm Myocardial Infarction with Normal Coronaries study.

OBJECTIVES: Myocardial infarction with angiographically normal coronary arteries (MINCA) is an important subtype of myocardial infarction; however, the prevalence, underlying pathophysiology, prognosis and optimal management of this condition are still largely unknown. Cardiovascular magnetic resonance (CMR) imaging has the potential to clarify the underlying pathology in patients with MINCA. The objective of this study was to investigate the diagnostic value of CMR imaging in this group of patients. DESIGN: The prospective, multicentre, observational Stockholm Myocardial Infarction with Normal Coronaries (SMINC) study. SETTING: Coronary care units in the Stockholm metropolitan area. SUBJECTS: Patients between 35 and 70 years of age with MINCA were consecutively included in the screening phase of the SMINC study. All patients had a typical clinical presentation, fulfilling the universal definition of myocardial infarction and had normal coronary angiography finding. Patients with known structural or coronary heart disease or other known causes of elevated troponin levels were excluded. RESULTS: In total, 176 patients with MINCA were screened from 2007 to 2011. Of these, 152 underwent CMR imaging. The investigation was performed a median of 12 (interquartile range 6-28) days after hospital admission; 67% of the findings were normal, whereas 19% of patients had signs of myocardial necrosis and 7% had signs of myocarditis. The remaining patients (7%) had either unrecognized hypertrophic cardiomyopathy or could not be classified. CONCLUSION: In this consecutive series of patients with MINCA, CMR imaging may help to differentiate between those with myocarditis, myocardial necrosis and normal myocardium. The incidence of MINCA was higher than previously reported. After excluding cases of myocarditis, MINCA consists of a large group of patients with normal CMR imaging results and a smaller group with myocardial necrosis. The aetiologies of these different imaging findings need to be explored.

Risk factors for myocardial infarction with normal coronary arteries and myocarditis compared with myocardial infarction with coronary artery stenosis.

The interest and awareness of myocardial infarction with normal coronary arteries (MINCA) have increased recently due to the frequent use of coronary angiography, the description of Takotsubo stress cardiomyopathy, and new sensitive troponin analyses. The prevalence of MINCA in all patients with myocardial infarction (MI) was registered during a 3-month period in the Stockholm metropolitan area in Sweden. The results showed that MINCA is more common than previously thought (7%) and affecting one third of every woman with MI. Patients with myocarditis were younger and more often presented with signs of inflammation such as elevated C-reactive protein and fever. Myocarditis constitutes an important differential diagnosis for coronary artery disease. There is a need for larger studies of MINCA, including investigation with cardiac magnetic resonance imaging, to establish prevalence and pathological process in this important subgroup of MI.

Myocardial infarction with angiographically normal coronary arteries.

Myocardial Infarction with Normal Coronary Arteries (MINCA) is an important subgroup of myocardial infarction with a frequency of at least 3-4% of all myocardial infarctions. The interest and awareness of MINCA have increased recently due to the frequent use of coronary angiography, the description of Takotsubo stress cardiomyopathy and new sensitive troponin assays. Since myocarditis may mimic myocardial infarction it is essential to exclude this in patients with myocardial infarction with angiographically normal coronary arteries. Cardiac magnetic resonance imaging is a cornerstone not only to establish the diagnosis but also an important tool in the search for different causes of myocardial damage. In the future, atherosclerotic burden, hemostatic function, characterization of stressors and inflammation will be important targets for research in this group of patients.

Cardiac repolarization and its relation to ventricular geometry and rate in reverse remodelling during antihypertensive therapy with irbesartan or atenolol: results from the SILVHIA study.

Hypertensive left ventricular (LV) hypertrophy is associated with a substantial risk for malignant arrhythmias and sudden death. According to recent results, antihypertensive therapy with the angiotensin II type 1 receptor blocker irbesartan reverses both structural and electrical remodelling. However, the relation between the LV geometric pattern (concentric vs eccentric) and electrical reverse remodelling has not been characterized, neither has the relation between repolarization and rate (QT/RR and JT/RR relation), which presumably reflects the propensity for bradycardia-dependent ventricular arrhythmia. In this study, repeat echocardiographic and electrocardiographic measurements were performed in hypertensive patients with LV hypertrophy, randomized to double-blind therapy with irbesartan (n = 44) or the beta(1)-adrenoceptor blocker atenolol (n = 48) for 48 weeks; 53 patients had concentric and 39 eccentric LV hypertrophy. In addition, 37 matched hypertensive subjects without LV hypertrophy and no current therapy served as controls. Irbesartan induced structural and electrophysiological reverse remodelling, independent of LV geometry. In contrast, atenolol had similar beneficial effect only in patients with concentric LV hypertrophy, while the response in those with eccentric hypertrophy was unfavourable with both prolonged repolarization time and an increased QT/RR slope (suggesting reverse-use dependence). In conclusion, there is a significant geometry-related difference in the reverse remodelling processes induced by irbesartan and atenolol. Echocardiographic characterization of the geometry in hypertension-induced LV hypertrophy might become an important step in the selection of optimal antihypertensive therapy.

Irbesartan reduces common carotid artery intima-media thickness in hypertensive patients when compared with atenolol: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) study.

BACKGROUND AND PURPOSE: Angiotensin II promotes cell growth and has been implicated in the development and maintenance of left ventricular (LV) hypertrophy and of structural vascular changes. We wished to examine whether an angiotensin receptor blocker (ARB) would influence structural vascular changes beyond the effects of blood pressure reduction. METHODS: Hypertensive patients with LV hypertrophy (age 55 +/- 9 years, blood pressure 162 +/- 19/104 +/- 8 mmHg, LV mass index 148 +/- 31 g m(-2); mean +/- SD) were randomized double-blind to the ARB irbesartan (n=52) or the beta(1) receptor blocker atenolol (n=56) for 48 weeks. Ultrasonography of the left and right common carotid artery (CCA) and echocardiography were performed at week 0 and 48. RESULTS: With similar reductions in blood pressure, CCA intima-media thickness (IMT) was reduced by irbesartan (from 0.92 +/- 0.14 by 0.01 +/- 0.10 mm, NS), whereas it was increased by atenolol (from 0.94 +/- 0.21 by 0.03 +/- 0.12 mm, P=0.018; P=0.002 between groups). CCA lumen diameter was less reduced by irbesartan than by atenolol. Thus, CCA intima-media area was reduced by irbesartan (from 21.3 +/- 5.0 by 0.90 +/- 2.45 mm(2), P=0.034) but not by atenolol (from 21.3 +/- 6.1 by 0.18 +/- 2.71 mm(2), NS; P=0.037 between groups). Changes in CCA IMT or area did not relate to changes in LV mass. CONCLUSIONS: The favourable effects by irbesartan on CCA IMT with an outward vascular remodelling suggest that angiotensin II mediates structural vascular changes, beyond the effects of blood pressure. This may be important in the prevention of cerebrovascular events.

Nurse-recorded clinic and ambulatory blood pressures correlate equally well with left ventricular mass and carotid intima-media thickness.

OBJECTIVE: To assess relationships between noninvasive ambulatory blood pressure (BP), clinic BP (mean value of three readings in the seated position measured by nurses), structural cardiac indices, intima-media thickness of the common carotid artery and several hormones. DESIGN: Cross-sectional study of 75 subjects with hypertension and left ventricular hypertrophy (HTH) according to echocardiography, 35 subjects with hypertension and normal left ventricular dimensions (HT) and 23 normotensive subjects (NT). RESULTS: We found an excellent correlation between mean 24-h ambulatory BP and clinic BP, the r-value for systolic BP being 0.82 and for diastolic levels 0.78 (both P < 0.0001). Clinic and ambulatory BP correlated equally well with left ventricular (LV) mass index (r-values between 0.55 and 0.64, all P < 0.0001) and to intima-media thickness of the carotid artery (r = 0.18-0.34, P < 0.01). The systolic white-coat effect (clinic BP - day-time BP) was higher in the HTH and HT compared with NT and was weakly correlated to LV mass index (r = 0.18, P = 0.04). Nondippers (mean arterial night/day BP ratio of > 0.9) had higher brain (6.1 +/- 7.5 pmol L(-1) vs. 3.7 +/- 3.2 pmol L(-1), P = 0.01) and atrial (14 +/- 3.4 pmol L(-1) vs. 9.3 +/- 5.4 pmol L(-1), P = 0.04) natriuretic peptide levels, and also exhibited a lower ejection fraction (49 +/- 8% vs. 57 +/- 9%, P = 0.006), than dippers. CONCLUSION: Clinic BP recordings performed by nurses as three measurements 1 min apart provide excellent relationship to target organ damage. Nondippers exhibited signs of a more advanced hypertensive organ damage than dippers which corresponds well with the poor prognosis linked to this condition.

Beta1-adrenergic receptor gene polymorphisms and response to beta1-adrenergic receptor blockade in patients with essential hypertension.

BACKGROUND: Studies suggest that the Ser49Gly and Arg389Gly polymorphisms in the beta1-adrenergic receptor might be of functional importance for the cardiovascular system. Both have been associated with altered receptor activity in vitro, and with hypertension and cardiac failure in vivo. HYPOTHESIS: The aim of this study was to test whether these polymorphisms were associated with the change in heart rate or blood pressure in patients with essential hypertension and left ventricular (LV) hypertrophy treated with the beta1-adrenergic receptor blocker atenolol. METHODS: Blood pressure and heart rate were measured in 101 hypertensive patients with echocardiographically verified LV hypertrophy, randomized in a double-blind study to treatment with either the beta1-adrenergic receptor blocker atenolol or the angiotensin II type I receptor antagonist irbesartan. Changes in blood pressure and heart rate were evaluated after 12 weeks. Beta1-adrenergic receptor genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: We found no significant associations between the changes in the measured variables and either of the two polymorphisms. However, carriers of the 49Gly allele showed a tendency toward a greater reduction in heart rate compared with patients with the Ser/Ser49 genotype (p = 0.06). CONCLUSIONS: The Ser49Gly and Arg389Gly beta1-adrenergic receptor polymorphisms do not seem to exert a major effect on the changes in heart rate and blood pressure during 12 weeks of treatment with atenolol in patients with essential hypertension and LV hypertrophy.

A single nucleotide polymorphism in the promoter region of the osteoprotegerin gene is related to intima-media thickness of the carotid artery in hypertensive patients. The Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA).

Osteoprotegerin (OPG) is a secreted member of the tumor necrosis factor receptor family, and in previous studies has been shown to regulate osteoclast activity and differentiation. Ablation of the OPG gene in mice results in calcification of the aorta and renal arteries. We have previously reported an association between a single nucleotide polymorphism in the promoter region of OPG and vascular morphology and function in healthy humans. The objective with this study was to confirm our previous results in a larger population, and in addition, to study subjects with hypertension. The OPG genotype was determined by restriction fragment length and the intima-media thickness (IMT) of the common carotid artery was measured by ultrasound in 100 patients with hypertension and left ventricular hypertrophy, and 75 healthy normotensive control subjects. In the hypertensive group subjects with the CC genotype (n=24) showed a significantly increased IMT compared to those with the TC (n=52, p=0.007) and TT (n=24, p=0.009) genotype, in the hypertensive group only (mean +/- SD for TT=0.88 +/- 0.21 mm, TC=0.90 +/- 0.16 mm, CC=1.05 +/- 0.31 mm). The allele distribution did not differ between hypertensive and control individuals. The present study confirms our previous finding and shows that polymorphism in the promoter region of OPG is associated with vascular morphology in hypertensive subjects.

Gender-specific association between preproendothelin-1 genotype and reduction of systolic blood pressure during antihypertensive treatment--results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA).

BACKGROUND: Studies suggest that endothelin-1 contributes to the pathogenesis of hypertension. A G5665T gene polymorphism of preproendothelin-1 has been shown to be associated with higher blood pressure in overweight patients. No study has yet determined the effect of this polymorphism on the change in blood pressure during antihypertensive treatment. HYPOTHESIS: This study aimed to determine this effect in hypertensive patients with left ventricular (LV) hypertrophy during antihypertensive treatment with either irbesartan or atenolol. METHODS: We determined the preproendothelin-1 genotype using minisequencing in 102 patients with essential hypertension and LV hypertrophy verified by echocardiography, randomized in a double-blind fashion to treatment with either the AT1-receptor antagonist irbesartan or the beta1-adrenoceptor antagonist atenolol. RESULTS: The change in systolic blood pressure (SBP) after 12 weeks of treatment was related to the preproendothelin-1 genotype in men; after adjustment for potential covariates (age, blood pressure, and LV mass index at study entry, dose of irbesartan/atenolol, and type of treatment), those carrying the T-allele responded on average with a more than two-fold greater reduction than those with the G/G genotype (-21.9 mmHg 13.9] vs. -8.9 [2.3], p = 0.007). No significant differences in blood pressure change between G/G and carriers of the T-allele were seen among women. CONCLUSIONS: Our finding suggests a gender-specific relationship between the G5665T preproendothelin-1 polymorphism and change in SBP in response to antihypertensive treatment with irbesartan or atenolol, suggesting the endothelin pathway to be a common mechanism included in the hypertensive action of the drugs.

Blood pressure and left ventricular geometric pattern determine diastolic function in hypertensive myocardial hypertrophy.

Abnormal left ventricular (LV) diastolic relaxation is an early sign of hypertensive heart disease. Whether LV diastolic dysfunction is caused directly by raised blood pressure, or by structural changes related to LV hypertrophy remains controversial. We examined 115 hypertensive patients with LV hypertrophy, and two age- and gender-matched groups (38 hypertensive patients without LV hypertrophy and 38 normotensive subjects) by echocardiography to assess determinants of LV diastolic function, and the relation between diastolic function and LV geometric pattern. Diastolic function was evaluated by the E/A-ratio, E wave deceleration time (E-dec), isovolumic relaxation time (IVRT), and the atrioventricular plane displacement method (AV-LA/AV-mean). A multivariate analysis (including gender, age and body mass index) shows diastolic function to be inversely related to blood pressure, LV wall thickness and LV mass, but not to LV end diastolic diameter. The E/A-ratio generally showed the strongest relations. Only the E/A-ratio and AV-LA/AV-mean were related to heart rate. By stepwise regression analysis, age was the strongest determinant for the E/A-ratio, E-dec and AV-LA/AV-mean, followed by systolic blood pressure, heart rate and LV wall thickness. For IVRT, however, LV wall thickness appeared strongest, followed by systolic blood pressure and age. In conclusion, blood pressure and LV wall thickness both have independent influence on LV diastolic function. Age and blood pressure are the most important factors to determine the E/A-ratio and E-dec, whereas LV geometry and blood pressure are most important when IVRT is used. AV-LA/AV-mean may not be useful in hypertensive LV hypertrophy.

Relationships between left ventricular mass and the renin-angiotensin system, catecholamines, insulin and leptin.

OBJECTIVES: Several neurohormonal systems have been suggested to stimulate myocardial cell growth, and thus take part in the development of left ventricular (LV) hypertrophy. We studied associations between LV mass and markers of the renin-angiotensin-aldosterone system (RAAS), the sympathetic nervous system, glucose homeostasis and leptin. DESIGN: A total of 115 hypertensive patients with LV hypertrophy and two age- and gender-matched control groups consisting of 38 hypertensive patients without LV hypertrophy and 38 normotensive subjects were included. We examined determinants of the RAAS, plasma levels and 24-h urinary excretions of noradrenaline and adrenaline, plasma proinsulin, insulin, glucose, leptin and LV mass by echocardiography. RESULTS: Plasma renin activity (PRA) and serum aldosterone were higher (both P < 0.001) in the LV hypertrophy group than in patients without LV hypertrophy and normotensive subjects (1.0 +/- 0.8, 0.2 +/- 0.2 and 0.2 +/- 0.2 ng mL(-1) h(-1), and 327 +/- 126, 269 +/- 146 and 221 +/- 80 pmol L(-1), respectively). PRA and aldosterone both related (P < 0.001) to LV mass index (r = 0.44 and 0.27, respectively). Catecholamine levels and excretions were similar in all three groups and did not relate to LV mass index. Proinsulin, insulin and leptin levels were all elevated in the hypertensive patients (P < 0.01), but proinsulin, insulin, insulin sensitivity (by the homeostasis model assessment) and leptin did not relate to LV geometry, when indexed for body size. CONCLUSIONS: Plasma renin activity and serum aldosterone levels are elevated in hypertensive LV hypertrophy and relate to LV mass index. In addition to blood pressure, activation of the RAAS may be an important nonhaemodynamic mechanism in the control of LV hypertrophy.

Angiotensin converting enzyme gene polymorphism predicts blood pressure response to angiotensin II receptor type 1 antagonist treatment in hypertensive patients.

OBJECTIVES: To determine whether polymorphisms in the renin-angiotensin system can predict blood pressure-lowering response to antihypertensive treatment; more specifically, in response to treatment with irbesartan or atenolol. DESIGN AND METHODS: Eighty-six patients with hypertension were randomized to double-blind treatment with either the angiotensin II type 1 receptor antagonist irbesartan or the beta1 adrenergic receptor blocker atenolol and followed for 3 months. We analysed angiotensinogen T174M and M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor A1166C polymorphisms and related them to blood pressure reduction. RESULTS: The mean reductions in blood pressure were similar for both treatments. In the irbesartan group, individuals homozygous for the ACE gene I allele showed a greater reduction in diastolic blood pressure, exceeding those with the D allele (-18 +/- 11 SD versus -7 +/- 10 mmHg, P = 0.0096). This was not the case during treatment with atenolol, and the interaction term between type of treatment and ACE II genotype was significant (P = 0.0176). The angiotensinogen and angiotensin II type 1 receptor polymorhisms were not related to the response to treatment. CONCLUSIONS: ACE genotyping predicted the blood pressure-lowering response to antihypertensive treatment with irbesartan but not atenolol. Thus, specific genotypes might predict the response to specific antihypertensive treatment.

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.

Regression of left ventricular hypertrophy in human hypertension with irbesartan.

BACKGROUND: The Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA). OBJECTIVE: Angiotensin II induces myocardial hypertrophy. We hypothesized that blockade of angiotensin II subtype 1 (AT1) receptors by the AT1-receptor antagonist irbesartan would reduce left ventricular mass (as measured by echocardiography) more than conventional treatment with a beta blocker. DESIGN AND METHODS: This double-blind study randomized 115 hypertensive men and women with left ventricular hypertrophy to receive either irbesartan 150 mg q.d. or atenolol 50 mg q.d. for 48 weeks. If diastolic blood pressure remained above 90 mmHg, doses were doubled, and additional medications (hydrochlorothiazide and felodipine) were prescribed as needed. Echocardiography was performed at weeks 0, 12, 24 and 48. RESULTS: Baseline mean blood pressure was 162/ 104 mmHg, and mean left ventricular mass index was 157 g/m2 for men and 133 g/m2 for women. Systolic and diastolic blood pressure reductions were similar in both treatment groups. Both irbesartan (P < 0.001) and atenolol (P< 0.001) progressively reduced left ventricular mass index, e.g. by 26 and 14 g/m2 (16 and 9%), respectively, at week 48, with a greater reduction in the irbesartan group (P = 0.024). The proportion of patients who attained a normalized left ventricular mass (i.e. < or = 131 g/m2 for men and < or = 100 g/m2 for women) tended to be greater with irbesartan (47 versus 32%, P = 0.108). CONCLUSIONS: Left ventricular mass was reduced more in the irbesartan group than in the atenolol group. These results suggest that blocking the action of angiotensin II at AT1-receptors may be an important mechanism, beyond that of lowering blood pressure, in the regulation of left ventricular mass and geometry in patients with hypertension.

Evaluation of various electrocardiographic criteria for left ventricular hypertrophy in patients with stable angina pectoris: influence of using modified limb electrodes.

BACKGROUND: Left ventricular hypertrophy (LVH) in coronary heart disease is associated with poor prognosis. Electrocardiography (ECG) criteria for LVH, when using ECG with modified limb electrode positions, has not been validated in patients with angina pectoris. METHODS: Echocardiography and resting ECGs with modified limb electrode positions, i.e. with the limb leads placed on the abdomen instead of the extremities, were registered from 468 patients (295 men) with stable angina pectoris. To evaluate the influence of using modified limb electrode positions, ECGs with standard and modified limb electrode positions were compared in a control group consisting of 50 other patients. RESULTS: The ECG criteria for LVH according to the Perugia score, the Minnesota code and Romhilt & Estes reached the highest sensitivity values, 27-31% in men and 24-38% in women, while the sensitivities of different Cornell criteria were as low as 6-10% in men and 19-29% in women. In the control group, the R- and S-wave amplitudes of the precordial leads were only slightly changed, as expected, whereas those of the limb leads changed considerably. Based on these results, we corrected aVL in the main study, which increased the sensitivity of the Cornell voltage criteria from 15 to 30%, while the specificity was maintained at 95%. CONCLUSIONS: ECGs registered with modified limb electrode positions can be used to detect LVH with traditional ECG criteria, but changes in the limb leads are considerable and influence the sensitivities.

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.

Angiotensin II type 1 (AT1) receptor blockade in hypertensive women: benefits of candesartan cilexetil versus enalapril or hydrochlorothiazide.

The aim of this large, randomized, double-blind, parallel-group study in hypertensive women was to compare the antihypertensive efficacy and effects on subjective symptoms and quality of life of the new angiotensin II type 1 (AT1) receptor blocker candesartan cilexetil, the angiotensin-converting enzyme inhibitor enalapril, and the diuretic hydrochlorothiazide (HCTZ). Women, aged 40 to 69 years, with a seated diastolic blood pressure (DBP) of 95 to 115 mm Hg, were randomized to candesartan cilexetil, 8 to 16 mg (n = 140), enalapril, 10 to 20 mg (n = 146), or HCTZ, 12.5 to 25 mg (n = 143), for 12 weeks; the higher doses were used if DBP was greater than 90 mm Hg after 6 weeks. Candesartan cilexetil lowered seated blood pressure by 17/11 and 19/11 mm Hg after 6 and 12 weeks of treatment, respectively. This reduction was greater (P < .01) than with enalapril (12/8 and 13/9 mm Hg) or HCTZ (12/7 and 13/8 mm Hg). The proportions of patients with controlled DBP (< 90 mm Hg) after 12 weeks of treatment with candesartan cilexetil, enalapril, or HCTZ were 60%, 51%, and 43%, respectively. Patients experienced less dry cough (P < 0.001) with candesartan cilexetil or HCTZ than with enalapril. No treatment differences were found in the incidence of dizziness and quality of life was well maintained in all groups. Compared with candesartan cilexetil and enalapril, HCTZ increased uric acid and decreased serum potassium (P < .001). In conclusion, candesartan cilexetil reduced blood pressure more effectively and was better tolerated than enalapril or HCTZ in women with mild to moderate hypertension.

Left ventricular hypertrophy is associated with an attenuated endothelium-dependent vasodilation in hypertensive men.

To investigate the relationship between left ventricular hypertrophy (LVH) and endothelium-dependent vasodilation (EDV), 30 untreated hypertensive patients, 18 treated hypertensives (53 +/- 7 years, all males) and 26 age-and sex-matched healthy normotensive controls, underwent evaluation of EDV and endothelium-independent vasodilation (EIDV) in the forearm, by means of local intra-arterial infusions of methacholine (MCh, evaluating EDV) and sodium nitroprusside (SNP, evaluating EIDV). Forearm blood flow was measured by venous occlusion plethysmography and LVH was measured by echocardiography. The reduction in forearm vascular resistance during MCh infusion (4 microg/min) was significantly smaller in the hypertensive patients with LVH when compared to those without LVH, both in the untreated (-61 +/- 12%, n = 19 vs -72 +/- 4%, n = 11, p < 0.01) and in the treated group (-60 +/- 15%, n = 11 vs -75 +/- 5%, n = 7, p < 0.01). Thereby, EDV was significantly impaired only in the hypertensive patients with LVH when compared to controls (-77 +/- 7% at MCh 4 microg/min, p < 0.001). EIDV was not significantly different between patients with and without LVH and controls. In conclusion, the presence of LVH was related to endothelial dysfunction, both in untreated and treated hypertensive patients, suggesting either a role for endothelial function in the development of LVH, or that a dysfunctional endothelium and LVH are coexisting markers of a more severe hypertensive disease.

Influence of age and cardiovascular factors on regional pulsed wave Doppler myocardial imaging indices.

AIMS: To describe the influence of age and other cardiovascular factors on regional pulsed wave Doppler myocardial imaging (DMI), and to compare DMI with conventional transmitral echocardiography and the atrioventricular plane displacement (AVPD) method. METHODS AND RESULTS: Eighty-eight healthy subjects aged 20-81 years were examined by DMI, performed in the intraventricular septum just below the mitral annulus and in the corresponding lateral region, by transmitral pulsed wave Doppler echocardiography, and by AVPD. The DMI peak velocity during the left ventricular (LV) early filling phase (e), decreased with age from 12.3 +/- 2.3 cm/s in the youngest to 7.0 +/- 1.7 cm/s in the oldest tercentile (r=- 0.76, P<0.001). The DMI peak velocity during atrial contraction (a), increased from 7.5 +/- 2.2 cm/s in the youngest to 9.7 +/- 1.7 cm/s in the oldest tercentile (r=0.41, P<0.001). The DMI systolic peak velocity (s), decreased with age from 8.2 +/- 1.1 (youngest tercentile) to 6.9 +/- 1.1 (oldest tercentile), r=-0.39, P<0.001 cm/s, while the fraction shortening of the LV increased from 33.7 +/- 4.1 to 38.2 +/- 5.9% (r=0.36, P<0.01). The DMI e/a correlated with the transmitral early/atrial (E/A) (r=0.83, P<0.001) and with the AVPD measurement of diastolic function AV-LA/AV-mean (r=0.82, P<0.001). The DMI e velocity correlated with the transmitral E velocity (r=0.38, P<0.001). In the multiple regression analysis of DMI e, age was the strongest factor and LV mass index correlated inversely and independently with e. No DMI variables were influenced by gender, while transmitral E correlated with gender. The LV dimension variables explained 35% (R2 adjusted) of the DMI e velocity changes; only 7% of the transmitral E changes were explained by those variables. CONCLUSION: Regional DMI indices are highly age-dependent. In comparision with conventional echocardiography, regional DMI might be more influenced by LV geometry and by myocardial structural changes. These findings suggest a complementary role for regional DMI to conventional echocardiography for the assessment of myocardial function.

Endothelium-dependent vasodilatation in treated and untreated hypertensive subjects.

It has repeatedly been shown that endothelium-dependent vasodilatation (EDV) is impaired in patients with untreated hypertension. The effect of antihypertensive treatment on EDV has, however, not been extensively investigated. In the present study, EDV and endothelium-independent vasodilatation (EIDV) were studied in 20 untreated and 41 treated hypertensive subjects and in 26 matched, normotensive controls by means of infusion of methacholine (MCh), 2 and 4 microg/min, evaluating EDV, and nitroprusside (SNP), 5 and 10 microg/min, evaluating EIDV, in the brachial artery. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. The vasodilatory action of MCh was impaired in untreated hypertensives compared with controls, with the response in the treated hypertensives in between the other two groups (p < 0.01 vs both of the other groups). EIDV, on the other hand, was enhanced in the treated hypertensives (p < 0.01), so that the MCh to SNP FBF ratio, an index of endothelial function, was attenuated in both treated and untreated hypertensives (0.97 +/- 0.24 and 0.96 +/- 0.15, respectively), compared with controls (1.27 +/- 0.29, p < 0.001). Both EDV and EIDV declined with increasing number of antihypertensive drugs used in the treated hypertensives (p < 0.05). In conclusion, the endothelial function index was found to be similarly depressed in both treated and untreated hypertensive subjects compared with normotensive controls. Antihypertensive therapy seems to improve the vasodilatory capacity in general rather than enhancing endothelial function.