Valeria Milazzo

Drugs and Orthostatic Hypotension: Evidence from Literature

Orthostatic hypotension is defined as the reduction of systolic blood pressure of at least 20 mmHg or the dropping of diastolic blood pressure of at least 10 mmHg within 3 minutes of standing compared to baseline values. It can be divided into neurogenic and non neurogenic forms. Neurogenic forms are caused by a primitive damage to autonomic nervous system, while drugs are the most common cause of non neurogenic orthostatic hypotension; they may also complicate or aggravate neurogenic forms. Many drugs can determine orthostatic hypotension, including both cardiovascular drugs and therapies used for neurological and psychiatric disorders. This effect is furthermore enhanced by multiple pharmacological treatments. It is important for the clinician to know the potential hazard of orthostatic hypotension, in order to avoid syncope, falls, hypoperfusion symptoms, excess of mortality and loss of compliance to treatment.

Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure: Comparison With Essential Hypertension

Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P=0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P =0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P =0.93); both parameters were significantly lower in healthy controls ( P <0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P =0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability. # Novelty and Significance {#article-title-49}

Cardiovascular complications in patients with autonomic failure

Patients with autonomic failure are characterized by orthostatic hypotension, supine hypertension, high blood pressure variability, blunted heart rate variability, and often have a “non-dipping” or “reverse dipping” pattern on 24-h ambulatory blood pressure monitoring. These alterations may lead to cardiovascular and cerebrovascular changes, similar to the target organ damage found in hypertension. Often patients with autonomic failure are on treatment with anti-hypotensive drugs, which may worsen supine hypertension. The aim of this review is to summarize the evidence for cardiac, vascular, renal, and cerebrovascular damage in patients with autonomic failure.

Orthostatic hypotension in a cohort of hypertensive patients referring to a hypertension clinic

The prevalence of orthostatic hypotension (OH) in hypertensive patients ranges from 3 to 26%. Drugs are a common cause of non-neurogenic OH. In the present study, we retrospectively evaluated the medical records of 9242 patients with essential hypertension referred to our Hypertension Unit. We analysed data on supine and standing blood pressure values, age, sex, severity of hypertension and therapeutic associations of drugs, commonly used in the treatment of hypertension. OH was present in 957 patients (10.4%). Drug combinations including α-blockers, centrally acting drugs, non-dihydropyridine calcium-channel blockers and diuretics were associated with OH. These pharmacological associations must be administered with caution, especially in hypertensive patients at high risk of OH (elderly or with severe and uncontrolled hypertension). Angiotensin-receptor blocker (ARB) seems to be not related with OH and may have a potential protective effect on the development of OH.

Ventricular repolarization before and after treatment in patients with secondary hypertension due to renal-artery stenosis and primary aldosteronism

A prolonged QT interval is a risk factor for ischemic heart disease in hypertensive subjects. Patients with renal-artery stenosis and primary aldosteronism (PA) are at increased risk of cardiovascular events. The objective of the present study was to evaluate the QT interval in patients with renovascular hypertension (RV) and PA before and after treatment. A total of 24 patients with RV and 38 with PA were studied; 89 patients with essential hypertension (EH) served as control group. Corrected QT intervals (QTcH) were measured from a 12-lead ECG. Basal QTcH was longer in RV (429±30 ms) and PA (423±23 ms) compared with EH controls (407±18 ms; P<0.001). The prevalence of QTcH >440 ms was higher in RV (29%) and PA patients (29%) compared with EH controls (4%; P<0.001). QTcH interval was evaluated after treatment in 19 RV and 15 PA patients. QTcH was reduced after renal-artery angioplasty in RV patients (419±14 ms; P=0.02), and after spironolactone or adrenalectomy in PA (403±12 ms; P=0.01). In conclusion, QT interval was prolonged in patients with RV and PA compared with controls with EH. After angioplasty of renal-artery stenosis in RV, and treatment with spironolactone or adrenalectomy in PA, the cardiovascular risk of such patients may be reduced by concomitant blood pressure lowering and QT duration shortening.

The role of autonomic dysfunction in cirrhotic patients before and after liver transplantation. Review of the literature

In patients affected by hepatic cirrhosis, autonomic dysfunction is a common finding; usually it is asymptomatic but it may correlate with increased mortality and morbidity before, during and after liver transplant, due to hemodynamic instability in the course of stressful events like sepsis, gastrointestinal bleeding and reperfusion after transplantation surgery. Hyperdynamic circulation and hepatic dysfunction seem to play a role in the pathogenesis of autonomic dysfunction, even if pathophysiological mechanisms are not completely known. We present a revision of previous literature about prevalence, pathophysiological mechanisms, clinical features, and mortality and morbidity of autonomic dysfunction secondary to hepatic cirrhosis.

Reverse blood pressure dipping as marker of dysautonomia in Parkinson disease

INTRODUCTION We sought to evaluate if the presence of abnormal circadian loss of nocturnal blood pressure dipping (reverse dipping) is associated with cardiovascular dysautonomia, a major source of morbidity in Parkinson disease. METHODS Consecutive Parkinson disease patients were enrolled in this cross-sectional study between January 2015 and June 2017. All subjects underwent same-day autonomic testing and 24-h ambulatory blood pressure monitoring. Cardiovascular dysautonomia was defined by the presence of at least one moderate or severe cardiovagal and adrenergic test abnormality. RESULTS We recruited 114 PD patients (79 males; mean age 64 ± 10 years; disease duration 6 ± 4 years). Cardiovascular dysautonomia was present in 32% (36/114). The blood pressure patterns were normal dipping in 28.9% (n = 33), extreme dipping in 6.1% (n = 7), reduced dipping in 32.5% (n = 37), and reverse dipping in 32.5% (n = 37). Reverse dipping was disproportionately prevalent in subjects with cardiovascular dysautonomia (69% vs 15%, p < 0.001). The diagnostic accuracy of reverse dipping in discriminating cardiovascular dysautonomia (AUC 0.791, specificity 84%, sensitivity 69%) was higher than that of bedside blood pressure ascertainment of neurogenic orthostatic hypotension (0.681, 66%, 69%) and supine hypertension (0.641, 78%, 50%). CONCLUSIONS Reverse nocturnal blood pressure dipping is a marker of cardiovascular dysautonomia in Parkinson disease, which can be screened for with ease and affordability using ambulatory blood pressure monitoring.

Cardiac Organ Damage and Arterial Stiffness in Autonomic Failure

Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P=0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P =0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P =0.93); both parameters were significantly lower in healthy controls ( P <0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P =0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability. # Novelty and Significance {#article-title-49}

[PP.33.07] CARDIAC ORGAN DAMAGE IN PARKINSONIAN PATIENTS WITH NOCTURNAL HYPERTENSION AND AUTONOMIC NEUROPATHY

Objective: Patients with autonomic neuropathy (AN) in Parkinsons disease (PD) often show nocturnal hypertension and reverse dipping pattern on ambulatory blood pressure (BP) monitoring (ABPM), and orthostatic hypotension. The aim of this study is the comparison of cardiac organ damage in reverse and non-reverse dipping PD and hypertensive patients. Design and method: 19 PD patients with reverse dipping on ABPM and no previous history of hypertension were compared to 19 non-reverse PD patients, matched for age and 24-hours mean BP, and 19 essential hypertensive patients matched for nocturnal mean BP. None of the PD and hypertensive patients suffered from diabetes, dyslipidemia, chronic kidney disease, sleep apnea and previous cardiovascular diseases. None of the patients were treated with antihypertensive or antihypotensive drugs. Reverse dipping was defined as day-night BP difference <0% on ABPM; nocturnal hypertension was considered as night systolic and diastolic BP >=120/70 mmHg. Left ventricular (LV) hypertrophy was defined as LV mass index >= 115 g/m2 in males and >= 95 g/m2 in females. Results: 36.8% of PD patients were women and the mean age was 70 years. 84.2% of reverse PD patients suffered from AN and nocturnal hypertension. Reverse PD patients showed similar 24-hours BP but higher nocturnal systolic and mean BP values than non-reverse PD patients. None of hypertensive patients had a reverse dipping pattern, but 84.2% revealed nocturnal hypertension. In reverse PD LV mass index was significantly increased than non-reverse PD patients (respectively 90.21 ± 25.26 vs 77.43 ± 13.32 g/m2, p = 0.04), and was similar to essential hypertensive patients (91.64 ± 24.78, p = 0.92), although remaining within normal limits. LV hypertrophy was detected in 5 reverse PD patients and 4 hypertensive patients, and none non-reverse PD patients (p = 0.046). No other significant differences in systolic and diastolic function were found between PD and hypertensive groups. Nocturnal mean BP and nocturnal systolic BP load were found to be the strongest predictors of higher LV mass index (p = 0.04, p = 0.045). Figure. No caption available. Conclusions: Reverse dipping and nocturnal hypertension are related to higher LV mass and increased finding of LV hypertrophy in PD patients.

Cardiac Organ Damage and Arterial Stiffness in Autonomic FailureNovelty and Significance

Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P=0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P=0.93); both parameters were significantly lower in healthy controls (P<0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P=0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability.Autonomic failure (AF) is characterized by orthostatic hypotension, supine hypertension, and increased blood pressure (BP) variability. AF patients develop cardiac organ damage, similarly to essential hypertension (EH), and have higher arterial stiffness than healthy controls. Determinants of cardiovascular organ damage in AF are not well known: both BP variability and mean BP values may be involved. The aim of the study was to evaluate cardiac organ damage, arterial stiffness, and central hemodynamics in AF, compared with EH subjects with similar 24-hour BP and a group of healthy controls, and to evaluate determinants of target organ damage in patients with AF. Twenty-seven patients with primary AF were studied (mean age, 65.7±11.2 years) using transthoracic echocardiography, carotid-femoral pulse wave velocity, central hemodynamics, and 24-hour ambulatory BP monitoring. They were compared with 27 EH subjects matched for age, sex, and 24-hour mean BP and with 27 healthy controls. AF and EH had similar left ventricular mass (101.6±33.3 versus 97.7±28.1 g/m2, P =0.59) and carotid–femoral pulse wave velocity (9.3±1.8 versus 9.2±3.0 m/s, P =0.93); both parameters were significantly lower in healthy controls ( P <0.01). Compared with EH, AF patients had higher augmentation index (31.0±7.6% versus 26.1±9.2%, P =0.04) and central BP values. Nighttime systolic BP and 24-hour systolic BP predicted organ damage, independent of BP variability. AF patients develop hypertensive heart disease and increased arterial stiffness, similar to EH with comparable mean BP values. Twenty-four–hour and nighttime systolic BP were determinants of cardiovascular damage, independent of BP variability. # Novelty and Significance {#article-title-49}