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S Julius

Publications and source records attributed to S Julius.

At least 19 recordsLinked to original sources

Regression of electrocardiographic left ventricular hypertrophy predicts regression of echocardiographic left ventricular mass: the LIFE study.

The electrocardiogram (ECG) is widely used for detection of left ventricular hypertrophy (LVH). However, whether changes in ECG LVH during antihypertensive therapy predict changes in LV mass remains unclear. Baseline and year-1 ECGs and echocardiograms were assessed in 584 hypertensive patients with ECG LVH by Sokolow-Lyon or Cornell voltage-duration product criteria at entry into the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiographic substudy. A >/=25% decrease in Cornell product defined regression of ECG LVH; a <25% decrease defined no significant regression; and an increase defined progression of ECG LVH. Regression of echocardiographic LVH was defined by a >/=20% reduction in LV mass. After 1 year of therapy, 155 patients (27%) had regression of ECG LVH, 286 (49%) had no significant change, and 143 (25%) had progression of ECG LVH. Compared with patients with progression of ECG LVH, patients with no significant decrease and patients with regression of ECG LVH had stepwise greater absolute decreases in LV mass (-16+/-33 vs -29+/-37 vs -32+/-41 g, P<0.001), greater percent reductions in LV mass (-5.7+/-14.6 vs -11.3+/-13.6 vs -12.3+/-15.6%, P<0.001), and were more likely to decrease LV mass by >/=20% (11.2 vs 24.8 vs 36.1%, P<0.001), even after adjusting for possible effects of baseline and change in systolic and diastolic pressures. Compared with progression of ECG LVH, regression of the Cornell product ECG LVH is associated with greater reduction in LV mass and a greater likelihood of regression of anatomic LVH.

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Long-term plasma catecholamines in patients with hypertension and left ventricular hypertrophy treated with losartan or atenolol: ICARUS, a LIFE substudy.

Hypertension is a major risk factor for morbidity and mortality. Plasma catecholamines are linked to the pathogenesis of hypertension. Pharmacological intervention, including treatment with beta-blockers, reduces cardiovascular mortality and morbidity. In the Losartan Intervention For Endpoint reduction in hypertension (LIFE) study, the angiotensin receptor blocker losartan significantly reduced cardiovascular end points compared to the beta-blocker atenolol. Thus, for the first time, one drug was shown to be superior to another in hypertension. The present substudy examined the effects of atenolol vs losartan treatment on plasma catecholamines at rest and during hyperinsulinaemia in a cohort of 86 LIFE patients. Plasma adrenaline increased significantly from placebo treatment at baseline to year 1 of treatment (P<0.0001), and also during hyperinsulinaemia (P<0.0001). Plasma noradrenaline did not change significantly from placebo treatment at baseline to year 1, but increased significantly during hyperinsulinaemia both at baseline and at year 1 (P<0.0001 for both). There were no differences in plasma catecholamines or the relative changes between the two treatment arms at any stage. In a subset of 42 patients examined also at years 2 and 3, these findings were confirmed during long-term treatment. Thus, losartan had an effect on plasma catecholamines comparable to that with the beta-blocker atenolol in patients with hypertension and left ventricular hypertrophy at rest and during hyperinsulinaemia. We find it unlikely that a difference in sympathetic activity explains the outcome benefits of losartan over atenolol in the LIFE study.

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Alcohol consumption and cardiovascular risk in hypertensives with left ventricular hypertrophy: the LIFE study.

The Losartan Intervention For End point reduction in hypertension (LIFE) study showed superiority of losartan over atenolol for reduction of composite risk of cardiovascular death, stroke, and myocardial infarction in hypertensives with left ventricular hypertrophy. We compared hazard ratios (HR) in 4287 and 685 participants who reported intakes of 1-7 and >8 drinks/week at baseline, respectively, with those in 4216 abstainers, adjusting for gender, age, smoking, exercise, and race. Within categories, clinical baseline characteristics, numbers randomized to losartan and atenolol, and blood pressure (BP) lowering were similar on the drug regimens. Overall BP control (<140/90 mmHg) at end of follow-up was similar in the categories. Composite end point rate was lower with 1-7 (24/1000 years; HR 0.87, P<0.05) and >8 drinks/week (26/1000 years; HR 0.80, NS) than in abstainers (27/1000 years). Myocardial infarction risk was reduced in both drinking categories (HR 0.76, P<0.05 and HR 0.29, P<0.001, respectively), while stroke risk tended to increase with >8 drinks/week (HR 1.21, NS). Composite risk was significantly reduced with losartan compared to atenolol only in abstainers (HR 0.81 95% confidence interval, CI (0.68, 0.96), P<0.05), while benefits for stroke risk reduction were similar among participants consuming 1-7 drinks/week (HR 0.73, P<0.05) and abstainers (HR 0.72, P<0.01). Despite different treatment benefits, alcohol-treatment interactions were nonsignificant. In conclusion, moderate alcohol consumption does not change the marked stroke risk reduction with losartan compared to atenolol in high-risk hypertensives. Alcohol reduces the risk of myocardial infarction, while the risk of stroke tends to increase with high intake.

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Are left ventricular mass, geometry and function related to vascular changes and/or insulin resistance in long-standing hypertension? ICARUS: a LIFE substudy.

Vascular hypertrophy and insulin resistance have been associated with abnormal left ventricular (LV) geometry in population studies. We wanted to investigate the influence of vascular hypertrophy and insulin resistance on LV hypertrophy and its function in patients with hypertension. In 89 patients with essential hypertension and electrocardiographic LV hypertrophy, we measured blood pressure; insulin sensitivity by hyperinsulinaemic euglucaemic clamp; minimal forearm vascular resistance (MFVR) by plethysmography; intima-media cross-sectional area of the common carotid arteries (IMA) by ultrasound; and LV mass, relative wall thickness (RWT), systolic function and diastolic filling by echocardiography after two weeks of placebo treatment. LV mass index correlated to IMA/height (r=0.36, P=0.001), serum insulin (r=-0.25, P<0.05), plasma glucose (r=-0.34, P<0.01), and showed a tendency towards a correlation to insulin sensitivity (r=0.21, P=0.051), but was unrelated to MFVR. Deceleration time of early diastolic transmitral flow positively correlated to IMA/height (r=0.30, P<0.01). The ratio between early and atrial LV filling peak flow velocity negatively correlated to MFVR(men) (r=-0.30, P<0.05). Endocardial and midwall systolic LV function were not related to vascular hypertrophy, plasma glucose, serum insulin or insulin sensitivity. In conclusion, insulin resistance was not related to LV hypertrophy or reduced LV function. However, high thickness of the common carotid arteries was associated with LV hypertrophy and high deceleration time of early diastolic transmitral flow. High MFVR was associated with low ratio between early and atrial LV filling peak flow velocity. This may suggest that systemic vascular hypertrophy contributes to abnormal diastolic LV relaxation in patients with hypertension and electrocardiographic LV hypertrophy.

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Heritability of left atrial size in the Tecumseh population.

BACKGROUND: Little is known about the determinants of atrial size, and no study has analyzed whether genetic factors are involved in the pathogenesis of LA enlargement. MATERIALS AND METHODS: We studied the heritability of echocardiographic left atrial size in 290 parents from the Tecumseh Blood Pressure Study and 251 children from the Tecumseh Offspring Study. All data from the parents and children were obtained at the same field office in Tecumseh, USA. Left atrial dimension was determined echocardiographically in accordance with American Society of Echocardiography guidelines with the use of leading-edge-to-leading-edge measurements of the maximal distance between the posterior aortic root wall and the posterior left atrial wall at end systole. RESULTS: For correlation between the left atrial dimensions of the parents and their offspring, several models were generated to adjust the atrial dimensions in both groups for an increasing number of clinical variables. After removing the effect of age, gender, height, weight, skinfold thickness, and systolic blood pressure, parent-child correlation for left atrial size was 0.19 (P = 0.007). Further adjustment for left ventricular mass and for measuring left ventricular diastolic function increased the correlation to 0.25 (P = 0.001). CONCLUSIONS: The present data indicate that heredity can explain a small but definite proportion of the variance in left atrial dimension.

Adolescent↗

Relationship of the electrocardiographic strain pattern to left ventricular structure and function in hypertensive patients: the LIFE study. Losartan Intervention For End point.

OBJECTIVES: This study was designed to assess the relation of electrocardiographic (ECG) strain to increased left ventricular (LV) mass, independent of its relation to coronary heart disease (CHD). BACKGROUND: The classic ECG strain pattern, ST depression and T-wave inversion, is a marker for left ventricular hypertrophy (LVH) and adverse prognosis. However, the independence of the relation of strain to increased LV mass from its relation to CHD has not been extensively examined. METHODS: Electrocardiograms and echocardiograms were examined at study baseline in 886 hypertensive patients with ECG LVH by Cornell voltage-duration product and/or Sokolow-Lyon voltage enrolled in the Losartan Intervention For End point (LIFE) echocardiographic substudy. Strain was defined as a downsloping convex ST segment with inverted asymmetrical T-wave opposite to the QRS axis in leads V5 and/or V6. RESULTS: Strain occurred in 15% of patients, more commonly in patients with than without evident CHD (29%, 51/175 vs. 11%, 81/711, p < 0.001). When differences in gender, race, diabetes, systolic pressure, serum creatinine and high density lipoprotein cholesterol were controlled, strain on baseline ECG was associated with greater indexed LV mass in patients with (152 +/- 33 vs. 131 +/- 32 g/m2, p < 0.001) or without CHD (131 +/- 24 vs. 119 +/- 22 g/m2, p < 0.001). In logistic regression analyses, strain was associated with an increased risk of anatomic LVH in patients with CHD (relative risk 5.14, 95% confidence interval [CI] 1.16 to 22.85, p = 0.0315), without evident CHD (relative risk 2.91, 95% CI 1.50 to 5.65, p = 0.0016), and in the overall population when CHD was taken into account (relative risk 2.98, 95% CI 1.65 to 5.38, p = 0.0003). CONCLUSIONS: When clinical evidence of CHD is accounted for, ECG strain is likely to indicate the presence of anatomic LVH. Greater LV mass and higher prevalence of LVH in patients with strain offer insights into the known association of the strain pattern with adverse outcomes.

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Relation of echocardiographic left ventricular mass and hypertrophy to persistent electrocardiographic left ventricular hypertrophy in hypertensive patients: the LIFE Study.

BACKGROUND: The Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) trial used left ventricular hypertrophy (LVH) on a screening ECG to identify patients at high risk for morbid events. Because of regression to the mean, not all patients who met screening criteria had persistent ECG LVH on the ECG performed at study baseline. METHODS: The relationship of echocardiographic LV mass and LVH to persistence or loss of ECG LVH between screening and baseline evaluation was examined in 906 hypertensive patients in the LIFE study, who had echocardiograms and additional ECG performed at study baseline. Patients were categorized according to the presence or absence of ECG LVH by Cornell voltage-duration product criteria or Sokolow-Lyon voltage criteria; echocardiographic LVH was defined by LV mass index (LVMI) > 104 g/m2 in women and > 116 g/m2 in men. RESULTS: A total of 678 patients (75%) had persistent ECG LVH at baseline evaluation. Compared with the 228 patients without ECG LVH on the second ECG by either criterion, the 106 patients with LVH by both Cornell product and Sokolow-Lyon criteria had significantly higher LVMI (140+/-31 v 114+/-21 g/m2, P < .001) and a higher prevalence of echocardiographic LVH (86% v 55%, P < .001). Patients with ECG LVH on the baseline ECG by either Cornell product criteria (n = 410) or Sokolow-Lyon voltage criteria (n = 162) had intermediate values of LVMI (125+/-25 and 121+/-21 g/m2) and prevalences of echocardiographic LVH (78% and 62%). After controlling for possible effects of age, sex, ethnicity, systolic blood pressure, and body mass index, persistence of ECG LVH on the baseline ECG was associated with an increased risk of echocardiographic LVH: compared with patients with neither ECG criteria for LVH, patients with only Sokolow-Lyon voltage criteria had a 1.2-fold increased risk of echocardiographic LVH, those with only Cornell product criteria had a 2.7-fold increased risk, and patients with both ECG criteria had a 4.1-fold increased risk of echocardiographic LVH (P < .001). CONCLUSIONS: Persistent ECG LVH between screening and LIFE study baseline identified patients with greater LV mass and a higher prevalence of echocardiographic LVH, suggesting that these patients may be at higher risk for subsequent morbid and mortal events.

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Antihypertensive treatment of patients with diabetes and hypertension.

Whereas individual research papers about antihypertensive treatment in diabetics might be somewhat confusing, the weight of the evidence strongly suggests that: 1) In patients with type 1 diabetes, it is advantageous to use angiotensin-converting enzyme (ACE) inhibitors as primary treatment. 2) In type 2 diabetics, aggressive blood pressure (BP) lowering is warranted and, the calcium antagonist controversy notwithstanding, all drugs appear to be similarly useful in reducing cardiovascular mortality. Specifically, in the Systolic Hypertension in Europe study, compared with placebo, a calcium antagonist dramatically reduced cardiovascular (CV) events in elderly diabetics. The Hypertension Optimal Treatment study showed that, using a calcium antagonist-based regimen, the degree of BP lowering determines the degree of CV event reduction. Furthermore, the United Kingdom Prospective Diabetes Study (UKPDS) did not find a difference in CV events reduction in patients treated with beta-blockers or with ACE inhibitors. In the UKPDS, the effect of BP lowering on reduction in CV events was more substantial than the degree of CV reduction by blood sugar lowering. 3) Both the CAPtopril Prevention Project (CAPPP) and the Heart Outcomes Prevention Evaluation (HOPE) studies found that treatment with an ACE inhibitor may be useful in reducing the incidence of new-onset type 2 diabetes mellitus. 4) Finally, insulin resistance, a precursor of diabetes mellitus and a strong predictor of future CV disease, is differentially affected by antihypertensive treatment. beta-Blockers and diuretics worsen insulin resistance, whereas alpha-adrenergic blockers and central imidazoline binding agents increase insulin sensitivity. The effect of ACE inhibitors and angiotensin blockers may also positively affect insulin resistance, but the results are not uniformly positive. It stands to reason that the differential effect of various drugs on insulin resistance and primary CV events may be clinically relevant particularly in the course of the long-term prevention of mild hypertension. All current trials investigate the effect of the treatment on secondary prevention of CV events among patients with advanced complicated diabetes and hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

Characteristics of 15,314 hypertensive patients at high coronary risk. The VALUE trial. The Valsartan Antihypertensive Long-term Use Evaluation.

Valsartan is an orally active, selective antagonist of the angiotensin II-1 (AT1) receptor developed for the treatment of hypertension. The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) Trial of Cardiovascular Events in Hypertension is a double-blind, randomized prospective, parallel group study designed to compare the effects of valsartan with those of the calcium-antagonist amlodipine on the reduction of cardiac morbidity and mortality. Patients with essential hypertension, aged 50 years and older, and at particularly high risk of coronary events were enrolled. 18,119 patients were screened and 15,314 patients in 31 countries were randomized mainly between January 1998 and December 1999. These hypertensives had a mean blood pressure of 154.7/87.5 mmHg at the time of their randomization to blinded medication. The population comprises both genders (men 57.6%), Caucasians (89.1%), mean age 67.2 years, mean body mass index 28.6 kg/m2, coronary heart disease (45.8%), high cholesterol (33.0%), type 2 diabetes mellitus (31.7%) and smokers (24.0%). More than 92% of the randomized participants had been treated for high blood pressure for at least 6 months when screened for the study. The randomized population is now being treated (goal blood pressure < 140/90 mmHg) in adherence with the protocol until at least 1450 patients experience primary cardiac endpoint defined as clinically evident or aborted myocardial infarction, hospitalization for heart failure or death caused by coronary heart disease.

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Home blood pressure monitoring. Current knowledge and directions for future research.

Home blood pressure (BP) monitoring has become popular in clinical practice and several automated devices for home BP measurement are now recommendable. Home BP is generally lower than clinic BP, and similar to daytime ambulatory BP. Home BP measurement eliminates the white coat effect and provides a high number of readings, and it is considered more accurate and reproducible than clinic BP. It can improve the sensitivity and statistical power of clinical drug trials and may have a higher prognostic value than clinic BP. Home monitoring may improve compliance and BP control, and reduce costs of hypertension management. Diagnostic thresholds and treatment target values for home BP remain to be established by longitudinal studies. Until then, home BP monitoring is to be considered a supplement. However, high home BP may support or confirm the diagnosis made in the doctor's office, and low home BP may warrant ambulatory BP monitoring. During long-term follow-up, home BP monitoring provides an opportunity for close attention to BP levels and variations. The first international guidelines have established a consensus document with recommendations, including a proposal of preliminary diagnostic thresholds, but further research is needed to define the precise role of home BP monitoring in clinical practice.

Blood Pressure Determination↗

Genetic contribution to the variance in left ventricular mass: the Tecumseh Offspring Study.

OBJECTIVE: To estimate the contribution of heredity to the variance in left ventricular mass (LVM), and to ascertain whether genetic factors may interact with non-genetic factors in promoting LVM growth. SUBJECTS AND SETTING: The study population consisted of 290 healthy parents and 251 healthy children living in Tecumseh, Michigan, USA. MAIN OUTCOME MEASURE: Correlation of parents' LVM with offspring's LVM adjusting for a number of clinical variables. METHODS: LVM in parents and offspring was measured with M-mode echocardiography by the same investigators. RESULTS: Parents unadjusted LVM was unrelated to offspring unadjusted LVM, but after removing the confounding effect of age, sex, anthropometric measurements, systolic blood pressure, plasma insulin and urinary sodium excretion, parent-child correlation for LVM was 0.28 (P = 0.006). The relative contribution of parental-adjusted LVM and of several offspring phenotypic and environmental variables on offspring LVM was evaluated by multivariable regression analysis. When age, gender, anthropometric measurements and systolic blood pressure were accounted for, adjusted LVM of parents explained only 1.6% of the total variance in offspring LVM. However, after inclusion of insulin and urinary sodium in the model heredity explained 7.6% of the total variance in offspring LVM, and its predictive power was second only to that of child's height. Furthermore, an interactive effect of parental LVM with offspring systolic blood pressure was found on child's left ventricular mass. CONCLUSION: Heredity can explain a small, but definite proportion of the variance in LVM. Higher blood pressure favors the phenotypic expression of the genes that regulate LVM growth.

Adolescent↗

Home blood pressure monitoring.

Hypertension is estimated to affect 43 to 56 million adults or 24% to 31% of the US population and is emerging as a major health problem in some countries in the Third World. Hypertension contributes to all the major atherosclerotic cardiovascular disease outcomes.

Blood Pressure Monitoring, Ambulatory↗

Prehypertension: a possible target for antihypertensive medication.

Vascular changes associated with elevated blood pressure may precede the clinical diagnosis of hypertension. Even after the diagnosis is made, associated coronary heart disease and renal disease continue to progress, despite adequate blood pressure control. Early treatment of blood pressure may reduce the incidence of clinical hypertension and reduce the long-term consequences of hypertension. Animal studies have shown that early blood pressure lowering, through blockade of the renin-angiotensin system, prevents long-term hypertension. Prevention is an important goal in the treatment of hypertension. Our best attempts to prevent hypertension use nonpharmacologic methods of diet and exercise. These methods are fraught with difficulties of implementation and compliance that limit their success. Finding novel approaches to prevent hypertension may have a major impact on the incidence of hypertension. We are investigating the effect of 2 years of treatment with an angiotensin receptor blocker (candesartan cilexitil) compared with placebo, followed by 2 years of follow-up, on the incidence of hypertension in patients with high-normal blood pressure. Incidence of hypertension after discontinuation of active treatment will be compared with the incidence in the placebo group. There will be 1000 patients enrolled in the study, which will be completed in 2004.

Angiotensin Receptor Antagonists↗

Autonomic imbalance, hypertension, and cardiovascular risk.

Essential hypertension conveys an increased risk of cardiovascular morbidity and mortality. The common finding of an autonomic imbalance in these patients contributes not only to the etiology of hypertension itself, but also to the cardiac risk and resulting adverse sequelae. A high sympathetic tone in particular is responsible for many of the metabolic, hemodynamic, trophic, and rheologic abnormalities that cluster in patients with high blood pressure. Methods to clarify the respective importance of prereceptor versus receptor abnormalities for the etiology of insulin resistance are warranted. Results of large hypertension clinical trials examining the degree of cardioprotection offered by newer medications that are neutral or beneficial to the vast array of underlying abnormalities are a few years away. In the meantime, utilization of antihypertensive drugs that reduce sympathetic overactivity and are metabolically beneficial is a reasonable clinical alternative in hypertensive patients with the metabolic syndrome or with signs of autonomic imbalance.

Autonomic Nervous System↗

Worldwide trends and shortcomings in the treatment of hypertension.

Despite advances in the availability and quality of antihypertensive medications and the institution of national programs to educate people about the seriousness of hypertension, much remains to be done. The percentages of people who are aware of their disease, are being treated for it, and are achieving adequate control of their blood pressure (BP) are disconcertingly low worldwide; surveys in numerous countries have consistently shown that fewer than 60% of affected people are being treated for hypertension and fewer than 30% have their BP adequately controlled. Reluctance on the part of many physicians to use antihypertensive therapy aggressively may be an impediment to improving these numbers. Further clinical trials are needed to assess the extent to which BP could be lowered safely and effectively with both single-agent and combination therapies.

Antihypertensive Agents↗

Lowering of blood pressure and predictors of response in patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint.

The Losartan Intervention For Endpoint (LIFE) reduction in hypertension study is a double-blind, prospective, parallel-group study comparing the effects of losartan with those of atenolol on the reduction of cardiovascular complications in patients (n = 9,194) with essential hypertension and with electrocardiographically (ECG) documented left ventricular hypertrophy (LVH). Baseline blood pressure was 174.4/97.8 mm Hg (mean), age 66.9 years, body mass index 28.0 kg/m2; 54.1% were women and 12.5% had diabetes mellitus. This population will be treated until at least 1,040 have a primary endpoint. After five scheduled visits and 12 months of follow-up, blood pressure decreased by 23.9/12.8 mm Hg to 150.5/85.1 mm Hg (target < 140/90 mm Hg). The mandatory titration level of < or = 160/95 mm Hg was reached by 72.1% of the patients. At the 12-month visit, 22.7% of all patients were taking blinded study drug alone, 44.3% were taking blinded drug plus hydrochlorothiazide (HCTZ), and 17.7% were taking blinded drugs plus HCTZ and additional drugs. Controlling for all other variables, patients in the US received more medication and had 2.4 times the odds of achieving blood pressure control than patients in the rest of the study (P < .001). Previously untreated patients (n = 2,530) had a larger initial decrease in blood pressure compared with those previously treated. Diabetics (n = 1,148) needed more medication than nondiabetics to gain blood pressure control. Only 13.9% of the patients had discontinued blinded study drug and 1.4% missed the revisit at 12 months. These data demonstrate both the successful lowering of blood pressure during 12 months of follow-up in a large cohort of patients with hypertension and LVH on ECG, but also emphasize the need for two or more drugs to control high blood pressure in most of these patients. Being previously treated and having diabetes were associated with less blood pressure response, whereas living in the US indicated better blood pressure control. It has been possible to keep most of these patients with complicated hypertension taking blinded study drug for 12 months.

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