The diagnostic approach and management of hypertension in the emergency department.

Hypertension urgency and emergency represents a challenging condition in which clinicians should determine the assessment and/or treatment of these patients. Whether the elevation of blood pressure (BP) levels is temporary, in need of treatment, or reflects a chronic hypertensive state is not always easy to unravel. Unfortunately, current guidelines provide few recommendations concerning the diagnostic approach and treatment of emergency department patients presenting with severe hypertension. Target organ damage determines: the timeframe in which BP should be lowered, target BP levels as well as the drug of choice to use. It's important to distinguish hypertensive emergency from hypertensive urgency, usually a benign condition that requires more likely an outpatient visit and treatment.

How low should blood pressure be in patients with chronic coronary and cerebrovascular diseases.

Over the last three decades, there are an increasing number of investigators and meta-analyses focusing on the fact that lowering blood pressure levels below a critical point is no longer beneficial and possibly even deleterious. In recent years, several trials and meta-analyses assessing intensive blood pressure (BP) lowering found that intensive treatment and lower blood pressure levels are associated with a reduction in CV events and mortality. However, a careful examination of the results shows that current data are not easily applicable to the general hypertensive population. In addition, recommendations of different guidelines since 2017 so far suggest different BP levels regarding the systolic and diastolic thresholds to be achieved and maintained, particularly in specific clinical situations such as patients with coronary artery disease and stroke. The challenge is to better define the limits of intervention and to define phenotypes of patients who are particularly vulnerable to over-aggressive lowering of blood pressure. This article reviews the evidence, controversies and current state of knowledge regarding intensive BP lowering and the lower thresholds of BP to be achieved in patients with chronic coronary or cerebrovascular diseases.

State of the art approach to managing angina and ischemia: tailoring treatment to the evidence.

Stable angina represents a chronic and often debilitating condition that affects daily activities and quality of life in patients with chronic coronary syndromes (CCS). Current European Society of Cardiology guidelines recommend a four-step approach for the medical treatment of patients taking into consideration hemodynamic variables (heart rate and blood pressure) and the presence or absence of left ventricular dysfunction. However, CCS patients often have several comorbidities and risk factors. Thus, a tailored approach that takes into consideration patient risk factors and comorbidities may have additional benefits beyond angina relief. This is a state of the art review of stable angina treatment based on the currently available evidence.

The ESC 2019 CCS guidelines: Have we left our patients and scientific evidence behind?

The ESC CCS 2019 guidelines recognize that successful management of anginal symptoms relies on effective therapy tailored to individual patient characteristics but do not provide any specific advice or clarity on how to utilize pharmacotherapy in order to achieve these goals. In this review, we are going to summarize and discuss the main points of disagreement.

Ivabradine and metoprolol in fixed dose combination: When, why and how to use it.

Heart rate is an important factor in coronary artery disease and its manifestations, and as such has been considered as a possible target for therapy. Although in epidemiological, and in less degree, in clinical studies derived indications of a possible pathogenetic role of heart rate in major cardiac diseases, clinical trials did not provided any strong evidence. However, even as a simple risk marker, remains important in the treatment of coronary artery disease and heart failure. Beta-blockers are the drugs most frequently used for heart rate control. However, recent studies constantly find insufficient effectiveness of beta-blockers in heart rate control and go further to question their efficacy on outcomes, making clear the need for an additional therapy. Ivabradine, a pure heart rate inhibitor, added to classic beta-blocker treatment represent the new therapeutic option in stable coronary disease and heart failure.

Atrial fibrillation and arterial hypertension.

Atrial fibrillation (AF) and arterial hypertension frequently coexist, not only because arterial hypertension increases the incidence of new onset of atrial fibrillation, but also because those two entities share common risk factors and conditions that increase the incidence of both. Thus, in our daily clinical practice we will often have to manage and treat those patients. In order to assess and treat these patients, proper blood pressure (BP) measurement as well as detection of atrial fibrillation is mandatory. The use of oscillometric devices for home and ambulatory blood pressure measurements may accurately measure systolic but not diastolic blood pressure levels. Current guidelines suggest to palpate the pulse and perform an electrocardiogram (ECG) as well as a long-term ECG monitoring in order to detect AF. However there is evidence that: the use of oscillometric BP device with a specific algorithm for the detection of AF as well as the interrogation of a permanent pacemaker may further help physicians to reveal periods of AF. Finnaly, although guidelines suggests the use of specific drugs in order to treat arterial hypertension in AF patients, the main goal is BP control per se. In this review, we are going to summarize the diagnostic work up of these patients namely the proper arterial blood pressure measurement, the detection of atrial fibrillation as well as the treatment of these patients based on the latest data of the literature.

Detrimental role of hyperuricemia on the cardio-reno-vascular system.

A bulk of evidence now exists that links gout with adverse cardiovascular (CV) outcomes. However, continuing doubt remains as to whether hyperuricemia can be truly considered an independent major CV risk factor. In fact, many gouty patients who develop major CV and renal events also possess several traditional CV risk factors, the presence of which can potentially confound any relationship between gout and adverse CV events. This paper reviews the available evidence to determine whether sufficient proof exists from biological, epidemiological and clinical trial studies to support a causal relationship between gout and major CV and renal events. This review is based on a PubMed/Embase database search for articles on hyperuricemia and its impact on cardiovascular and renal function.

Sympathetic overactivity in hypertension and cardiovascular disease.

From the first description of its anatomy by T. Willis to the novel therapeutic manipulations, it is unanimously recognized that the sympathetic nervous system (SNS) holds a crucial role in cardiovascular homeostasis. The introduction of sophisticated techniques, as microneurography and regional norepinephrine spillover provided the evidence for the role of sympathetic overactivity in various cardiovascular disease entities. Sympathetic activation is common in patients with essential hypertension and contributes to initiation, maintenance and progression of the disease and it contributes to the manifestation of its major complications. A considerable body of evidence relates SNS overactivity with high sodium intake in experimental animals and humans and the underlying mechanisms have nowadays been elucidated. SNS activity is more pronounced in patients with resistant hypertension and there are several conditions that lead to this phenomenon, as older age, kidney disease, obesity and metabolic syndrome, mental stress and sleep apnea. SNS overactivity holds also a key physiopathological role in heart failure, acute coronary syndromes and arrhythmias. Moreover, inhibition of sympathetic overactivity by various means, including central SNS suppressing drugs, peripheral alpha- and beta- adrenergic receptor blockers, or novel approaches as renal sympathetic denervation have been used successfully in the treatment of all these disorders.

The alpha2 -adrenergic receptors in hypertension and heart failure: experimental and clinical studies.

This is a brief overview of experimental and clinical studies exploring the hemodynamic functions of the alpha2A and alpha2B adrenergic receptor (AR) subtypes in animals submitted to genetic manipulations or gene treatment, as well as the clinical effects of central sympathetic suppression with the alpha2-AR agonist clonidine in patients with ischemic heart disease and/or heart failure. The animal experiments have led us to conclude that the sympathetic outflow is regulated by activation of the presynaptic alpha2A-AR subtype, which is the predominant alpha2-AR subtype in the central nervous system and exerts a sympathoinhibitory (hypotensive) action; on the contrary, activation of the central alpha2B-AR elicits a sympathoexcitatory response (such as seen in salt-induced hypertension, which requires functionally intact alpha2B-AR). Since there are no selective pharmacologic agents yet capable of discriminating among alpha2-AR subtypes, clinical studies utilize clonidine, the central sympathetic suppressant effect of which has been used for 35 years to treat hypertension. In small clinical trials, clonidine was used successfully for treatment of acute or chronic heart failure, acute myocardial infarct or hypertensive cardiomyopathy with subclinical diastolic dysfunction. We speculate that future development of agents capable of selectively activating the alpha2A-AR or blocking the alpha2B-AR may further improve our capability to treat hypertension, ischemic heart disease and heart failure.

Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension. Losartan Trial Investigators.

OBJECTIVE: The goal of this multicenter, double-blind, randomized, parallel-group study was to compare the effects of losartan potassium (hereafter referred to as losartan), candesartan cilexitil (hereafter referred to as candesartan), and losartan/hydrochlorothiazide (HCTZ) in patients with mild to moderate hypertension (sitting diastolic blood pressure [SiDBP] 95-115 mm Hg). METHODS: A total of 1161 patients were randomized in a 2:2:1 ratio to 12 weeks of treatment with losartan 50 mg QD, possibly titrated to 100 mg QD (n = 461); candesartan 8 mg QD, possibly titrated to 16 mg QD (n = 468); or losartan 50 mg QD, possibly titrated to losartan 50 mg plus HCTZ 12.5 mg QD (n = 232). At 6 weeks, the regimens of patients not reaching a goal SiDBP <90 mm Hg were titrated as described, whereas patients achieving this goal continued with low-dose monotherapy. The single primary end point at 12 weeks tested the equivalence of the 2 monotherapy regimens, predefined as a maximum between-treatment difference in the mean change from baseline trough SiDBP of 2.5 mm Hg. RESULTS: At 12 weeks, changes in SiDBP/sitting systolic blood pressure (SiSBP) of -12.4/-14.4 mm Hg with losartan 50 mg/100 mg and -13.1/-15.8 mm Hg with candesartan 8 mg/16 mg demonstrated equivalence between the 2 monotherapy regimens (95% CI for difference in SiDBP, -1.6 to 0.2). At 12 weeks, the losartan 50 mg/50 mg plus HCTZ 12.5 mg regimen had reduced SiDBP/SiSBP significantly more (-14.3/-18.0 mm Hg) than either the candesartan 8 mg/16 mg (SiDBP, P = 0.045; SiSBP, P = 0.017) or losartan 50 mg/100 mg regimen (SiDBP and SiSBP, P = 0.001). During the last 6 weeks, patients whose regimen had been titrated to losartan 50 mg plus HCTZ 12.5 mg (n = 114) showed a greater reduction in SiDBP/SiSBP (-14.5/ -18.7 mm Hg) than did those whose regimen had been titrated to either losartan 100 mg (-10.5/-12.3 mm Hg; n = 211) or candesartan 16 mg (-11.5/-13.2 mm Hg; n = 206), representing a clinically meaningful > or = 2.5-mm Hg) difference. All 3 treatments were well tolerated, with few patients experiencing drug-related adverse events (6.9% losartan 50 mg/100 mg, 7.5% candesartan 8 mg/16 mg, 3.0% losartan 50 mg/ 50 mg plus HCTZ 12.5 mg). Candesartan 8 mg/16 mg increased serum uric acid levels (0.13 mg/dL; 95% CI, 0.04 to 0.23), whereas losartan 50 mg/100 mg decreased them (-0.14 mg/dL; 95% CI, -0.24 to -0.04), and losartan 50 mg/50 mg plus HCTZ 12.5 mg left them unchanged (0.06 mg/dL; 95% CI, -0.07 to 0.20). CONCLUSIONS: Losartan 50 mg/100 mg and candesartan 8 mg/16 mg were comparable treatments in terms of blood pressure reduction. After titration, losartan 50 mg plus HCTZ 12.5 mg was superior to either candesartan 16 mg or losartan 100 mg in reducing hypertension. Losartan, but not candesartan, lowered serum uric acid levels and attenuated the expected increase in uric acid levels with HCTZ 12.5 mg.

Genetic predisposition to stroke in relatives of hypertensives.

BACKGROUND AND PURPOSE: The genetic basis of stroke is poorly understood. We evaluated patterns of familial aggregation of hypertension and stroke to test the hypothesis that inherited susceptibility to these disorders may be determined by a common set of factors. METHODS: Genealogical and medical history information was obtained for a cohort of 354 hypertensive probands ascertained in a clinic-based setting, their 1427 first-degree relatives, and 239 of their spouses. Risks of stroke and hypertension in biological and nonbiological relatives were compared with the logistic model of the generalized estimating equations adjusted for age and sex. RESULTS: The risk of hypertension was higher for the parents and siblings of the probands than for spouses (odds ratio [OR]=2.4; 95% CI, 1.8 to 3.4; OR=2.2; 95% CI, 1.6 to 3.0, respectively). When the spouses were used as a reference group, the risk of stroke for parents of the hypertensive probands was 7.3 times higher (OR=7.3; 95% CI, 3.6 to 14.8), while a nonsignificant but slightly increased risk for siblings (OR=1.6; 95% CI, 0.8 to 3.3) was observed. Controlling for hypertension, obesity, smoking, coronary heart disease, diabetes, and cholesterol resulted in decreased estimates of the risk of stroke for parents and siblings (OR(parents)=5.4; 95% CI, 2.6 to 11.2; OR(siblings)=1.2; 95% CI, 0.6 to 2.5). The risk of stroke was significantly higher for hypertensive parents and siblings than for nonhypertensive parents (OR=5.2; 95% CI, 2.8 to 9. 7) and siblings (OR=5.8; 95% CI, 2.1 to 15.9). A history of hypertension was not associated with an increased risk for stroke in spouses (OR=0.7; 95% CI, 0.2 to 3.1). The risk of stroke in hypertensive relatives of probands with stroke was higher than that of the normotensive relatives (OR=13.4). A less elevated risk ratio was observed in the relatives of probands who did not have a stroke (OR=4.0). CONCLUSIONS: Our data showing a higher occurrence of hypertension and stroke in parents of hypertensive probands compared with spouses suggest that some of the genetic factors predisposing to these conditions may be the same. The slightly increased risk to siblings compared with spouses was not significant, suggesting that elucidation of these factors through family studies of stroke may be difficult because of secular trends toward improved treatment for hypertension. Although a history of hypertension increases the risk of stroke among parents and siblings, multivariate analyses revealed a familial component to stroke independent of hypertension.

Chronic sympathetic suppression in the treatment of chronic congestive heart failure.

Previous short-term studies demonstrated that treatment with clonidine produced significant hemodynamic improvement in patients with congestive heart failure (CHF). In this study we followed 12 CHF patients (10 M, 2 F age 63+/-11, 10 with ischemic cardiomyopathy and 2 with dilated cardiomyopathy) treated with 0.15 or 0.075 mg oral clonidine twice daily for 13+/-5 months (range 6-23). with functional evaluation at baseline, 6 weeks and 6 months. There was suppression of circulating catecholamines, associated with significant ameliorations in NYHA class, in duration of exercise tolerance (from 246+/-68 sec to 362+/-30 and 459+/-70 sec, respectively p < 0.02), in ejection fraction (from 32+/-7% to 35+/-5 and 39+/-7% p < 0.04) and in left ventricular enlargement as assessed echocardiographically. There were also improvements in a number of electrophysiologic parameters calculated by computerized analysis of ambulatory ECG tapes, such as heart rate variability, indicating diminished propensity to malignant arrhythmias, as confirmed by decreases in the numbers of isolated premature ventricular contractions, couplets and episodes of non-sustained ventricular tachycardia. The data suggest that chronic central sympathetic suppression with clonidine in CHF results in significant functional amelioration and improved electrophysiologic stability.

Comparison of spirapril, isradipine, or combination in hypertensive patients with left ventricular hypertrophy: effects on LVH regression and arrhythmogenic propensity.

This study was designed to evaluate in 45 hypertensive patients with left ventricular hypertrophy (LVH) the effects of a 6-month course with one of three different antihypertensive regimens (the calcium channel blocker isradipine, the angiotensin converting enzyme inhibitor spirapril in monotherapy, or a combination of the two drugs, n = 15 per group) on blood pressure, LVH regression, and various functional correlates of LVH. All three treatment modalities decreased significantly LV mass index by an average of 10%, although the combination had the greatest blood pressure-lowering effect and spirapril had the least, as assessed by office resting pressures, ambulatory monitoring, and isometric grip testing. There was no correlation between magnitude of blood pressure lowering and degree of LVH regression. The effects of treatment on pressor hormone profiles differed among groups, as spirapril tended to suppress angiotensin II and norepinephrine, whereas isradipine had opposite effects. Exercise tolerance was prolonged by all three regimens, but significantly more by the combination. All three regimens decreased significantly the double product by 10% to 15%. Indices of electrophysiologic stability calculated from analysis of ambulatory electrocardiogram exhibited significant improvement in several parameters such as QRS duration, presence of late potentials, and measures of heart rate variability, resulting in fewer episodes of simple or complex ventricular arrhythmia. We conclude that all three regimens produce significant LVH regression associated with improved functional capacity and electrical stability. These results reflect the sum of the differential hemodynamic and hormonal effects exerted by each treatment modality.

Hemodynamic and humoral correlates in essential hypertension: relationship between patterns of LVH and myocardial ischemia.

While evaluating 45 hypertensive patients with left ventricular hypertrophy (LVH) for enrollment in a clinical research protocol, we had the opportunity to compare anatomic and functional characteristics of those with LVH and ischemia on an exercise tolerance test (ETT), but without coronary artery disease by angiography (group I, n=8), versus those with a normal ETT (group II, n=37). There were no differences in age, sex, severity, and duration of hypertension between the two groups, but group I patients were significantly more overweight and had a worse lipid profile. Blood pressure at peak ETT was higher in group I despite shorter exercise duration, although resting and ambulatory pressures were similar. Group I patients had evidence of more pronounced cardiac enlargement and LVH by both ECG and echo criteria and a characteristic pattern of more pronounced thickening at the apex, but both groups had equally good systolic function and similar degrees of mild diastolic dysfunction. Analysis of 24-hour ambulatory ECG showed a significantly greater propensity to ventricular arrhythmias in group I, as shown by the presence of late potentials in 4 patients, the presence of couplets in 3, runs of ventricular tachycardia in 2 (while none of group II patients had late potentials or complex arrhythmias), and an average frequency of isolated premature ventricular contractions approximately three times higher in group I than group II patients. Our data demonstrate that hypertensives with LVH associated with myocardial ischemia at stress but with normal coronary arteriograms tend to be more overweight, attain a higher systolic blood pressure at ETT despite a shorter duration, have a higher propensity for severe arrhythmias, and have an adverse lipid profile. LVH in these subjects is more pronounced by both ECG and echo criteria and is characterized by predominantly apical hypertrophy with left atrial and ventricular dilatation rather than overall LV wall thickening.