Nondihydropyridine Calcium Antagonists Research Articles

279 LAYERED PLAQUES: NOT ALL ARE HEALED

Abstract Layered plaques are the effect of a previous plaque event. They are associated with coronary spasm and found in more than 50% of patients with stable angina and a quarter of those with an acute coronary syndrome. Nevertheless, it is not clear whether their presence is indicative of a healing process or rather is predictive of an increased risk of future events. A 71-year-old male, heavy smoker and hypertensive, presented with episodes of angina at rest that resolved spontaneously in less than 5 minutes, with evidence of ST-segment elevation (STE) in the lower leads during one of these episodes. Coronary angiography showed an intermediate stenosis at the end of the mid segment of the dominant right coronary artery (RCA) (Figure A). Optical coherence tomography (OCT) revealed a layered plaque, consisting of high backscattering layers alternated with low reflection layers (Figures A1-3). Given the minimum luminal area of 3.65 mm2 and the absence of other criteria for plaque instability (erosion, thin-cap, etc.), we treated the patient conservatively with medical therapy alone, consisting of a single antiplatelet agent and a high-dose statin with ezetimibe. A non-dihydropyridine calcium antagonist and a long-acting nitrate were started given the suspicion of coronary spasm. Four months later the patient returned to the emergency department for persistent oppressive chest pain unresponsive to sublingual nitrates with evidence of STE in the lower leads. Emergency coronary angiography showed an acute occlusion of RCA with TIMI 0 flow in correspondence to the layered plaque highlighted 4 months earlier on OCT (Figure B). Antegrade flow was restored with manual thrombus aspiration (Figure C) and OCT showed lesion progression with many new layers, together with a cavity suggestive of plaque rupture (Figures C1-3). A 3.5×38 mm everolimus eluting stent was deployed – based on OCT sizing – and post-dilated with a 4.0×8 mm non-compliant balloon, obtaining an excellent angiographic result with TIMI 3 flow (Figure D). Low-reflecting layers within layered plaques are generally considered to be lipid deposits, but they could also represent intraplaque haemorrhages, generated by coronary spasm. The haematoma can be reorganised within the plaque to create a new layer, leading to lesion progression without necessarily requiring a loss of endothelial integrity. The progressive increase of the haematoma may lead to plaque rupture when the pressure exceeds the resistance of superficial layers. This case reveals a new possible mechanism of plaque progression in patients with coronary spasm and explains how layered plaques can be ambivalently considered to be either stable or vulnerable. Their treatment should be meticulously tailored not only based on classical criteria of plaque instability but also according to the underlying trigger mechanism.

Analysis of adherence to therapy and compliance of outpatient treatment with the EURO FORTA system in elderly and senile polymorbid patients with CHF

Abstract Introduction Chronic heart failure (CHF) is one of the main reasons for hospitalization in the elderly. Various scales and algorithms have been proposed to combat polypharmacy. Purpose To assess adherence to therapy and compliance of outpatient treatment with the EURO FORTA system. Methods The study included 313 patients admitted to the city center for the treatment of CHF from February 1, 2019 to October 1, 2020 at the age of 75±8.22 years. In all patients, the Charlson comorbidity index and the number of diseases (1–2, 3–5, >5) were calculated. Outpatient treatment was assessed according to the EURO FORTA system (2018) in patients (over 65 years old – n=274, over 60 years old and ≥6 drugs – n=39) with CHF depending on the level of polymorbidity, age, sex, CHF variant and its severity. Heart failure was diagnosed in 66.77% of patients with preserved ejection fraction (EF), in 19.81% – with intermediate, in 13.42% - with low. Results Depending on the class of drugs according to the EURO FORTA system, 5 groups of patients were identified: 1st (received only class A drugs) – 3.51% of patients; 2nd (A, B)-22.36%; 3rd (A, B and C)-17.25%; 4th (A, B, C and D) – 27.17%; 5th – not taking medications on an outpatient basis 29.71%. In almost all groups at the outpatient stage, patients with>5 diseases (pmg=0.020) prevailed (45.46–70.59%). At the outpatient stage in groups 1, 3 and 4 there were more patients with stage IIB CHF (63.64%, 51.86% and 47.06%) pmg=0.041, and in groups 2 and 5 – patients with stage IIA (58, 57% and 48.39%). Class C: digoxin (n=4, patients with atrial fibrillation (AF) and CHF), amiodarone (n=3, patients with AF), moxonidine (n=1, patient with hypertension), betablockers 3 years after myocardial infarction (MI) (n=2), spironolactone (n=23, CHF). Reception of spironolactone on an outpatient basis was associated with a high risk of developing acute kidney injury (AKI) p=0.01, AKI in CKD p=0.042, and AF p=0.03. Class D: non-steroidal anti-inflammatory drugs (NSAIDs) (n=68), aspirin for AF (n=2), class I-III antiarrhythmics (except amiodarone) (n=8), glibenclamide (n=1), nondihydropyridine calcium antagonists (n=2, patients with hypertension), dihydropyridine antagonists (n=1, with ischemic heart disease 3 years after MI). Taking NSAIDs on an outpatient basis was associated with a high risk of AKI development p=0.033, as well as anemia p=0.036, including grade 3 and 4 anemia (WHO) p=0.042. Conclusion Every second patient with CHF had more than 5 diseases. Every third person did not take drug therapy at the outpatient stage. The frequency of taking drugs of classes C and D was higher in polymorbid patients. With a more severe course of CHF, patients more often took class D drugs. Among class D were NSAIDs (80%) and class I-III antiarrhythmics (except amiodarone) (9.4%) prevailed. The use of spironolactone on an outpatient basis was associated with a high risk of AKI and AF, and NSAIDs-with AKI and anemia. Funding Acknowledgement Type of funding sources: None.

Causes, Predisposing Factors and Prevention Directions of Drug-induced Bradycardia (Based on the Results of the Hospital Register of Oardiac Medications Overdoses STORM)

Aim. Analysis of drug-induced bradiarrhythmia (DIB) causes and predisposing factors, followed by the development of recommendations for practitioners on its prevention.Material and methods. The register included consistently all cases of hospitalization at the Regional Vascular Center (Ryazan) due to DIB in 2017 (n=114), 2018 (n=167), and retrospectively in 2014 (n=44). In total, 325 cases were reported: men - 26.1%, age 76.0 [68.0; 82.0] years; patients >65 years - 83.7%, and patients >75 years - 57.9%. The dose of medications with bradycardic action (BCA) taken the day before was known in 227 cases (69.8%), which allowed us to analyze the correctness of the intake regime in these cases.Results. The excess of a single and / or daily medication dose (absolute overdose, AOD) occurred only in 10.6% of cases and was associated with the patient's attempt to cope with the deterioration of the disease or an acute clinical situation on their own. In other cases, there was no formal violation of the Instructions, but there was an inhibition of the heart's conducting system activity, characteristic of an overdose of medication (the so-called "relative” overdose, ROD). It was due to the summation/potentiation of BCA of several medications or changes in the medication pharmacokinetics. There were no differences in the clinical and demographic characteristics of patients and the provision of medical care in the groups with AOD and ROD (p>0.05). The exception was a high frequency of bradycardia <40 beats / min in AOD group (75.0% vs 49.8%, p=0.019) and, as a result, - management in the conditions of the Intensive Care Unit (66.7% vs 39.9%, p=0.012). Frequency of pre-admission receiving medications in AOD and ROD groups also did not differ (p>0.05): beta-blockers - an average of 64.3%, antiarrhythmic drugs with BCA- 41.0%, cardiac glycosides 25.1% (frequency each of these medicationsin DIB cases over the 5-year period has not changed), an agonist of the 11-imidazoline receptors - moxonidine (12.3%, its frequency has increased 8.9 times in 5 years, p=0.004), non-dihydropyridine calcium antagonists - 7.9% (decrease frequency over 5 years 4.0 times, p=0.002), other - 16.7%. In 56.8% of cases, medications with BCA were used in combination. At admission, a decrease in glomerular filtration rate (GFR) <45 ml/min/1.73 m2 was registered in 56.8% of cases, <30 ml/min/1.73 m2 - in 31.8%, <15 ml/min/1.73 m2 -in 10.9% (differences between groups with p>0.05). Hospital lethality in the AOD group is 4.2%, in the ROD group- 5.4% (p>0.05).Conclusion. The main reasons of DIB are excess of the recommended dose, unrecorded summation/potentiation of BCA of several medications, and / or changes in the medication pharmacokinetics. Predisposing factors are self-medication of patients with worsening cardiovascular disease or acute clinical situations (e.g., hypertensive crisis), taking multiple medications with BCA, accession of heart disease, manifested by bradyarrhythmia, decrease in GFR, elderly and senile age.

Assessment of the effectiveness of antihypertensive therapy in the early post-stroke period of ischemic stroke based on indicators of arterial stiffness

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Globally, stroke is the second leading cause of death, leading to a reduction in life expectancy and disability of patients. It seems important to study and introduce into practical health care both new approaches to stroke prevention and measures aimed at full recovery in the post-stroke period. Purpose To assess the antihypertensive therapy (AHT) in patients with arterial hypertension (AH) in the early post-stroke period of ischemic stroke (IS), based on indicators of arterial stiffness. Methods The study included 180 patients with hypertension (mean age 64 years) in the acute period of ischemic stroke (IS). Inclusion criteria in this trial: AH, age over 40 years, time from the onset of stroke no more than 48 hours. Arterial stiffness was assessed by an oscillometric method with an assessment of the 24-hour reflected wave transit time (RWTT), aortic augmentation index (AIxao)), arterial stiffness index (ASI), and pulse wave velocity (PWV). The indicators were assessed at the time of admission, at the time of discharge from the hospital (14-21 days) and 2 months after discharge. We determined endothelin-1 (ET-1) levels by ELISA at admission and 2 months after discharge. Retrospectively, patients were divided into 5 groups depending on the prescribed AHT: group 1 (48 patients) - ACEIs/ARBs, thiazide-like diuretics (TLDs), group 2 (46 people) - ACEIs/ARBs, nondihydropyridine calcium antagonists (ACs) and beta-blockers (BBs), group 3 (39 people) - ACEIs/ARBs and ACs, group 4 (26 patients) - ACEIs/ARBs and BBs, group 5 (21 people) - ACEIs/ARBs, TLDs and BBs. Results AHT showed a positive trend in terms of arterial stiffness in all 5 groups. Compared with the baseline values, the significant decrease in PWV (12.4 ± 1.7m/s vs 10.9 ± 1.8m/s, p < 0.01), AIxao (39.8 ± 6.3% vs 36.8 ± 5,2%, p < 0.001), ASI (167.9(127.0;174.5) vs 158.8(115.0;168.7)), p < 0.05), increased RWTT (98.0 ± 9.8ms vs 105.3 ± 7.5ms) in group 2 of patients were found. After 2 months, when comparing indicators between groups the significant decrease in PWV to 9.1(8.7; 11.6)m/s, p < 0.01), AIxao to 31.7(29.8;41.9)%, p < 0.01, an increase in RWTT to 107.7(102.4; 110.2)ms, p < 0.01 in the group of patients taking ACEIs/ARBs, ACs and BBs were detected. After 2 months after discharge, a significant decrease of ET-1 was also observed in group 2 (5.8 ± 2.2ng/ml vs 4.2 ± 1.8ng/ml). The combination of ACEs/ARBs and BBs showed the least effectiveness in reducing arterial stiffness. Conclusions The combination of ACEIs/ARBs, ACs and BBs showed the greatest efficiency in reducing the stiffness in patients with hypertension in the early post-stroke period of IS. It seems important for the functional recovery of patients in the post-stroke period to use the drug therapy aimed not only at lowering blood pressure, but also favorably affecting the arterial stiffness.

Analysis of bioMARKer Distribution and Individual Reproducibility Under Rivaroxaban Treatment in Japanese Patients with Non-Valvular Atrial Fibrillation (R-MARK Study, CVI ARO2).

The "on-therapy range" of direct oral anticoagulants is the 90% interval of drug concentration. Previously, we reported the on-therapy range of rivaroxaban in a single-center cohort. The present study aimed to confirm the range and intraindividual reproducibility in a multicenter cohort.Eligible patients with non-valvular atrial fibrillation under rivaroxaban treatment for prevention of ischemic stroke were enrolled from nine institutes in Tokyo, Japan, between June 2016 and May 2017 (n = 324). The first and second (three months later) blood samples both taken within 1-5 hours after rivaroxaban intake were analyzed (n = 219). Plasma concentration of rivaroxaban (PC-Riv) and prothrombin time (PT) with five reagents were measured.The 90% interval of PC-Riv was 47.3-532.9 ng/mL. The 90% interval of PT measured with RecombiPlasTin 2G was 11.8-22.3 seconds, the widest range among the five reagents examined. PC-Riv reproducibility within a 90% interval was evaluated bidirectionally (first-to-second and second-to-first), and 92.4% of samples were reproducible. The change rate (CR) of PC-Riv between two samplings ranged widely, and high CR (≥54.3%, cutoff for predicting non-reproducibility) was predicted by concomitant drugs (non-dihydropyridine calcium antagonist and thiazide) and mitral regurgitation.We reported the on-therapy range of rivaroxaban in a multicenter cohort. This range was consistent with that of a single-center cohort and was highly reproducible within three months in daily clinical practice. However, caution is necessary regarding several factors that may affect the intraindividual variation of PC-Riv.

Results of the pilot part of the cardiac drug overdoses hospital registry (storm): focus on drug-induced bradycardia

Aim. Analysis of the relevance of drug-induced bradycardia (DIB) as a medical and social problem, its main regularities and determination of the need for further study of this issue.
 Materials and Methods. The register study was performed on 01 Jan 2017-30 Jun 2018 (18 months) at the clinical base of the Ryazan Regional Clinical Cardiology Dispensary. Inclusion criteria were: 1) bradycardia/bradyarrhythmia syndrome with intake of at least one drug with a bradycardic effect (BCE), 2) signing Informed consent to the processing of personal and clinical data. No additional interventions were performed in the diagnosis or treatment of patients within the registry.
 Results. During 18 months, 191 patients (age 77.0 [69.0;82.0] years, 26.7% of men) were hospitalized with a verified diagnosis of DIB, which accounted for 52.6% of all cases of hospitalization for drug overdose. During the analyzed period, there was an increase in both the total number of drug overdoses (1.7 times, p0.001) and overdoses of drugs with BCE (1.8 times, p0.001). Main clinical manifestations of DIB: reduced heart rate (50 beats/min 80.0%, 40 beats/min 51.1%), sinoatrial (30.4%) and atrioventricular blocks (1st degree 8.2%, 2nd degree 10.4%, 3rd degree 14.1%), syncope (32.6%) and cardiac pauses 3 s (7.4%). Almost all (94.8%) the patients were hospitalized by ambulance, 40.7% to the intensive care unit; 17.8% required pacemaker implantation; hospital mortality was 5.2%. More than half (54.5%) of hospitalized patients took 2 drugs with BCE, 15.7% 3 and 3.14% 4 (both in monotherapy and as a part of a combination): beta-blockers 68.4%, antiarrhythmic preparations 38.9%, digoxin 25.8%, non-dihydropyridine calcium antagonists 10.5%, I1-imidazoline receptor agonist 9.5%, and other drugs with BCE 7.4%. To analyze the cause of DIB, we used clinical data of 135 patients (age 77.0 [69.0;82.0] years, 20.7% of men), who could indicate the exact dose of a taken drug with BCE. Among them, the absolute exceedance of the recommended dose of drugs with BCE was found in 14.1% of cases, while in 85.9% of cases summation/potentiation effect of several drugs with ВСЕ was observed, with intake of each in a therapeutic dose.
 Conclusion. The study confirmed high medical and social significance of the problem of DIB, which requires attention of practitioners, pharmacologists and clinical pharmacologists, health care providers, and also continuation of its study.

Status of treatment for atrial fibrillation in a community health service center in Shanghai Pudong New Area

Objective To analyze the status of the treatment for atrial fibrillation (AF) in a community health service center in Shanghai Pudong New Area. Methods Clinical data of all patients with AF attended in Hudong Community Health Service Center of Shanghai Pudong from August 2016 to August 2017 were retrospectively reviewed. The gender, age, smoking history, drinking history, concomitant diseases, antithrombotic therapy, rhythm control, ventricular rate control drugs, health education, needs for setting up AF clinics in the community were analyzed. Result The study included 220 patients, with average age of (59.7±10.4) years; 34.1% (75/220) patients had hypertension and the blood pressure was controlled in 41.3% (31/75) ; 20.5% (45/220) patients had diabetes mellitus and glycosylated hemoglobin (HbA1c) was controlled well in 26.7% (12/45) . Three cases of mitral stenosis were treated with warfarin anticoagulation. Among 217 patients without valvular atrial fibrillation, 157 had thromboembolic risk score≥2, 20.4% (32/157) of whom used warfarin anticoagulation, 10.8% (17/157) used new oral anticoagulant (NOAG) and 58.1% (91/157) had never used warfarin or NOAG anticoagulation. The reasons were as follows:doctors did not prescribe (41.9%, 39/91), patients did not accept (35.2%, 32/91), and so on. There were 21.8% (48/220) of patients undergoing drug cardioversion, and 5.9% (13/220) undergoing electrical cardioversion. For control of ventricular rate, 55.9% (123/220) patients used beta blockers, 13.6% (30/220) used non-dihydropyridine calcium antagonists, and 23.6% (52/220) used digitalise. Less than 55% of patients were given health education of physical exercise, weight management and medicine use. For AF clinic in community hospital, 56.8% (125/220) of patients needed, and 17.3% (38/220) very need; 50.0% (110/220) patients trusted and 12.3% (27/220) very trusted in anticoagulation management in community hospitals. Conclusion The anticoagulant rate is relatively low, treatment of concomitant diseases is less satisfactory and the health education might be incomplete in the community surveyed in this study. Key words: Atrial fibrillation; Community health services; General practitioner; Treatment

Possibilities of using Fosinopril, an angiotensinconverting enzyme inhibitor, combined with Diltiazem, a non-dihydropyridine calcium antagonist, as first-line therapy in the treatment of arterial hypertension (clinical case)

The article exemplified the successful experience of using combination therapy consisting of fosinopril, an angiotensin-converting enzyme inhibitor, and diltiazem, a non-dihydropyridine calcium antagonist, in a patient with a history of arterial hypertension, sinus tachycardia and bronchial asthma. The authors proved the high antihypertensive efficacy and safety of the therapy, its favourable effect on the daily profile of blood pressure and heart rate, and strong organ-protective properties, the ability to reduce the degree of left ventricular hypertrophy and microalbuminuria level.

The Role of Ivabradine in the Management of Angina Pectoris.

Stable angina pectoris affects 2–4 % of the population in Western countries and entails an annual risk of death and nonfatal myocardial infarction of 1–2 % and 3 %, respectively. Heart rate (HR) is linearly related to myocardial oxygen consumption and coronary blood flow, both at rest and during stress. HR reduction is a key target for the prevention of ischemia/angina and is an important mechanism of action of drugs which are recommended as first line therapy for the treatment of angina in clinical guidelines. However, many patients are often unable to tolerate the doses of beta blocker or non-dihydropyridine calcium antagonists required to achieve the desired symptom control. The selective pacemaker current inhibitor ivabradine was developed as a drug for the management of patients with angina pectoris, through its ability to reduce HR specifically. The available data suggest that ivabradine is a well-tolerated and effective anti-anginal agent and it is recommended as a second-line agent for relief of angina in guidelines. However, recent clinical trials of ivabradine have failed to show prognostic benefit and have raised potential concerns about safety. This article will review the available evidence base for the current role of ivabradine in the management of patients with symptomatic angina pectoris in the context of stable coronary artery disease.

Inappropriate sinus tachycardia — ailment or disease?

We present a case of a 36-year-old female patient with a long history of persistent palpitations, limited exercise tolerance, and pre-syncope. ECG recordings revealed long lasting episodes of inappropriate sinus tachycardia (IST). IST is characterised by persistent cardiac arrhythmias with sinus P waves in the ECG, and an exaggerated response to a minimal physical effort or stress. Using 24-h Holter definition the average heart rate in patients with IST should be > 90 bpm or daytime heart rate > 100 bpm. The syndrome is associated neither with structural heart disease nor with any reversible causes of sinus tachycardia (i.e. fever, anemia, infection, hyperthyroidism, drug abuse). Therefore the diagnosis is generally one of exclusion. Beta-blockers are most frequently used as first line therapy. Other potentially effective drugs are nondihydropyridine calcium antagonists or ivabradine. The prognosis in patients with IST is very good but in some cases the symptoms can be severe and debilitating.

Protocolo terapéutico de las miocardiopatías restrictivas. Tratamiento en la obstrucción al tracto de salida del ventrículo izquierdo en la miocardiopatía hipertrófica

There is no protocolized treatment for restrictive cardiomyopathy; in cases of known etiology there are specific therapeutic measures, medical or surgical, and, in general, treatment of complications: heart failure and arrhythmias. It is not uncommon that is required in addition to the indicated drugs, devices such as pacemakers or defibrillators. In selected cases, when the prognosis depends on the cardiomyopathy, cardiac transplantation could be indicated.Obstruction of left ventricular outflow tract in hypertrophic cardiomyopathy is responsible for the symptoms, and sometimes, the prognosis of these patients. Pharmacological treatment is indicated with beta blockers and/or non-dihydropyridine calcium antagonists, the third option is the disopyramide. If symptoms persist, there is the possibility of invasive treatment, either surgical (septal myectomy that could be completed with intervention at mitral valve and subvalvular apparatus) or percutaneous (intracoronary alcohol septal ablation).

Factors Associated with Blood Pressure Control in Hypertensive Patients with Coronary Heart Disease: Evidence from the Chinese Cholesterol Education Program

Blood pressure (BP) remains poorly controlled among hypertensive patients with coronary heart disease (CHD) in China. Improvement of its management will require an understanding of the patient characteristics and treatment factors associated with uncontrolled hypertension. A cross-sectional survey of 3,279 patients from 52 centers in China was performed to examine potential barriers to adequate blood pressure control of hypertensive patients with CHD. Uncontrolled hypertension was defined as blood pressure ≥130/or 80 mmHg. Multivariable logistic regression was used to identify factors associated with poor blood pressure control. Mean age of the patients was 65 years, 40% were women, and mean BMI was 25 kg/m2. Mean systolic blood pressure was 136±18 mmHg and mean diastolic blood pressure was 80±11 mmHg. Only 18% of patients had a mean blood pressure <130/80 mmHg during the study period. Multivariate analysis revealed several independent factors of poor blood pressure control: body mass index ≥23 kg/m2, the presence of stable angina pectoris (SAP), family history of diabetes, and use of calcium channel blockers (CCB). Further analysis showed that non-dihydropyridine calcium antagonist was significantly correlated with low BP control rate. Some of these may be amenable to modification. The results of our study suggest that overweight, the presence of SAP and family history of diabetes are important factors for tight BP control in primary care. In addition, non-dihydropyridine calcium channel blockers appear less effective than other therapies in control of blood pressure and should not be the first choice among hypertensive patients with CHD. Further identification of patients at risk of poor BP control can lead to targeted interventions to improve management.

Management of Patients With Atrial Fibrillation (Compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS Recommendations)

This document is a compilation of the current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) practice guideline recommendations for atrial fibrillation (AF) from the “ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation),”* the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)”† and the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran).”‡ Updated and new recommendations from 2011 are noted and outdated recommendations have been removed. No new evidence was reviewed, and no recommendations included herein are original to this document. The ACCF/AHA Task Force on Practice Guidelines chooses to republish the recommendations in this format to provide the complete set of practice guideline recommendations in a single resource. ### 1.1. Pharmacological and Nonpharmacological Therapeutic Options #### 1.1.1. Rate Control During AF Class I 1. Measurement of the heart rate at rest and control of the rate using …

Role of Elevated Heart Rate in the Development of Cardiovascular Disease in Hypertension

That elevated heart rate (HR) is a risk factor for cardiovascular morbidity and mortality in healthy people as well as in patients with cardiac diseases is supported by numerous epidemiological association studies.1–4 Increased HR has been recognized as a negative prognostic factor independent of many other clinical parameters that can influence the HR, including physical activity scores, left ventricular function, or use of β-blockers. Thus, HR appears to satisfy all epidemiological criteria for being considered as a true risk factor, and its predictive value for cardiovascular disease appeared to be as strong as that of most important cardiovascular risk factors. This is particularly true for the results obtained in hypertensive patients. Elevated HR is a common feature among hypertensive individuals.1 Among the young hypertensive subjects participating in the HARVEST study, >15% had a baseline resting HR ≥85 bpm and 27% had a HR ≥80 bpm.5 According to the Tensiopulse study, which evaluated 38 145 patients cared for by 2000 general practitioners all across Italy, >30% of the hypertensive patients had a resting HR ≥80 bpm.6 In a large French population, untreated hypertensive subjects had approximately a 6-bpm faster HR than normotensive individuals.7 Elevated HR is frequently associated with high blood pressure (BP) and metabolic disturbances and increases the risk of new onset hypertension and diabetes.1 Many experimental data obtained both in animals and in human beings support the importance of HR as a true risk factor for atherosclerosis and cardiovascular disease, providing convincing evidence for this pathogenetic mechanism.1–3 The pathogenetic connection between HR and cardiovascular disease has been discussed in several reports1–3,8,9 and is beyond the scope of this review. ### High HR as a Precursor of Hypertension, Obesity, and Diabetes Numerous studies have demonstrated that tachycardia is frequently associated with hypertension in …

Effects of Antihypertensive Treatment on Endothelial Function

Essential hypertension is characterized by endothelial dysfunction due to reduced availability of nitric oxide (NO) secondary to increased generation of oxygen-free radicals. Some antihypertensive drugs may improve or restore endothelial function independently of their blood pressure lowering effect. The newer generation of β-blockers, such as nebivolol and carvedilol, which provide antioxidant activity, can improve endothelial function in patients with hypertension. Dihydropyridine and non-dihydropyridine calcium antagonists reverse impaired endothelium-dependent vasodilatation in different vascular districts, through a mechanism related to an antioxidant effect. However, conflicting results are found in the brachial artery. Angiotensin-converting enzyme (ACE) inhibitors improve endothelial function in subcutaneous, epicardial, brachial, and renal circulation, but they are ineffective in potentiating the impaired response to acetylcholine in the forearm of hypertensive patients. Angiotensin II receptor antagonists can restore endothelium-dependent vasodilatation to acetylcholine in subcutaneous microcirculation but not in that of the forearm muscle. They also improve basal NO release and decrease the vasoconstrictor effect of endogenous endothelin-1. Large-scale clinical trials are required to definitively demonstrate that treatment of endothelial dysfunction can improve the prognosis of patients with essential hypertension.

Dual RAAS blockade is desirable in kidney disease: Con

Dual renin-angiotensin aldosterone (RAAS) blockade is associated with higher risk of hyperkalemia and has not been shown, in any outcome trial of validated renal end points, that is, doubling of creatinine, time to dialysis, or death, to be superior over other approaches. It shows promise in advanced proteinuric nephropathy for additional proteinuria reduction. Whether this additional proteinuria reduction translates into meaningful outcomes of chronic kidney disease (CKD) is unknown, as proteinuria change is not a validated surrogate end point. Until we know the answer to this question, only those with very high levels of proteinuria should receive combination RAAS blocking therapy, and they need to be carefully monitored. Such individuals should be evaluated for risk of hyperkalemia and should consider use of a non-dihydropyridine calcium antagonist added to the single RAAS agent as an alternative for proteinuria reduction. This provides a safe and effective option for those patients with advanced nephropathic disease who need additional proteinuria reduction. In all cases other than advanced proteinuric nephropathy, there is no evidence of any positive CKD outcome with dual RAAS blockade. Thus, dual RAAS blockade cannot be recommended for all CKD patients.

Influence of microalbuminuria in achieving blood pressure goals

In all individuals with hypertension regardless of diabetes status, microalbuminuria is an independent risk marker for cardiovascular events including myocardial infarction, stroke and other conditions. While blood pressure reduction is important in reducing this marker in individuals with hypertension other factors such as salt intake play an important role in reducing oxidant stress and other factors related to the genesis of microalbuminuria. Clinical trials demonstrate that drugs interfering with the renin-angiotensin system--angiotensin-converting enzyme inhibitors and angiotensin receptor blockers--should be used as first-line antihypertensive therapy in patients with microalbuminuria because they seem to have a blood pressure-independent antiproteinuric effect. A combination of an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker or other classes of medications shown to decrease protein excretion, such as nondihydropyridine calcium antagonists or aldosterone receptor blockers, should be considered to decrease albuminuria further; beta-blockers with alpha-blocking properties such as carvedilol have also been shown to reduce microalbuminuria probably secondary to its antioxidant properties. This review provides a summary of current evidence regarding the associations of blood pressure with microalbuminuria, the rationale for currently recommended blood pressure goals, and the use of various classes of antihypertensive agents in proteinuric patients.

Pathophysiological role of heart rate: from ischaemia to left ventricular dysfunction

Myocardial ischaemia results from imbalance between myocardial oxygen demand and supply. An increase in heart rate (HR) will raise both demand and supply. HR is the most important determinant of myocardial oxygen consumption and of cardiac energy demand. HR reduction improves myocardial perfusion by increasing the fraction of the cardiac cycle occupied by diastole, which accounts for 80% of coronary flow. Besides these physiological characteristics, HR is also linked to the progression of atherosclerosis, at least in animals, and an increase in HR is associated with plaque rupture in humans. The symptom of chest pain in stable angina is almost always triggered by elevated HR owing to physical or emotional stress. Equally, an increased HR precedes an episode of asymptomatic or silent myocardial ischaemia. Therefore, it is not surprising that the efficacy of some anti-anginal drugs such as b-blockers and non-dihydropyridine calcium antagonists has been related to their effectiveness in reducing HR. In many studies, multivariate analysis has shown HR to be an independent predictor of mortality and of hospitalization for heart failure. A relationship has been found between HR reduction and mortality in patients with congestive heart failure treated with b-blockers. Thus HR is an important therapeutic target for ischaemia and left ventricular dysfunction or congestive heart failure, and it seems likely that relatively high HR is both causative and indicative of important pathophysiological processes: HR is a risk factor for cardiovascular morbidity and mortality throughout the cardiovascular continuum.

CALCIUM ANTAGONISTS IN CLINICAL PRACTICE: FOCUS ON METABOLIC AND VASCULAR EFFECTS

The efficacy of calcium antagonists widely used in cardiological practice is proved both by placebo-controlled studies and in comparative trials with end-point control. Calcium antagonists are the most effective vasoprotective medicines. In our study we had shown antihypertensive efficacy and ability to improve endothelium function of non-dihydropyridine calcium antagonist, diltiazem (Altiazem RR). Altiazem RR can be drug of choice in wide profile of patients with arterial hypertension, especially in those with concomitant metabolic abnormalities, diabetes mellitus and ischemic heart disease.

Angiographic Evaluation of High-Risk Treadmill Scores in Patients With Unstable Angina According to Sex, Age, or Use of Drugs With a Negative Chronotropic Effect

The aim of the study is to determine whether age, sex, or the use of drugs with a negative chronotropic effect modifies the sensitivity, specificity, positive or negative predictive value, or positive or negative likelihood ratio of the high-risk criteria used in exercise testing as defined by the Spanish Society of Cardiology (SEC) and the American College of Cardiology/American Heart Association (ACC/AHA), the Duke treadmill score, the Veterans Affairs and West Virginia prognostic score, or the ST/Heart Rate Index at the time when left main coronary artery disease, three-vessel disease or two-vessel disease involving the proximal left anterior descending artery is detected by coronary angiography. The study included a cohort of 469 consecutive patients aged 75 years who were admitted to hospital for unstable angina. All patients underwent exercise stress testing and coronary angiography. In all situations, the ACC/AHA high-risk criteria had the highest sensitivity, negative predictive value, and negative likelihood ratio, and the Duke Treadmill Score had the highest specificity and positive predictive value. The diagnostic accuracy of the other treadmill scores was affected by sex, age or the use of drugs with a negative chronotropic effect. The ACC/AHA high-risk criteria and Duke Treadmill Score provided useful additional information during the assessment of ST-segment depression. These measures could help improve the diagnostic accuracy of conventional ECG exercise testing in women, older individuals, and patients taking beta-blockers or non-dihydropyridine calcium antagonists.