Cardiovascular and renal function in normotensive and hypertensive patients with compensated cirrhosis: effects of posture

doi:10.1016/S0168-8278(99)80193-7

Journal of Hepatology

Volume 30, Issue 4, April 1999, Pages 632-638

https://doi.org/10.1016/S0168-8278(99)80193-7 Get rights and content

Abstract

Background/Aims: The aim of this study was to evaluate cardiovascular and renal function in patients with compensated cirrhosis and essential hypertension in the supine position and in response to standing up.

Methods: Twenty-four patients with compensated cirrhosis (12 with elevated arterial pressure) and 20 healthy volunteers underwent echocardiographic evaluation of left ventricular end-diastolic and stroke volumes, ejection fraction, cardiac index, arterial pressure, peripheral resistance, creatinine clearance and sodium excretion in both the supine and the standing position.

Results: When supine, only normotensive patients had a hyperdynamic circulation, with increased left ventricular end-diastolic and stroke volumes, cardiac index, and ejection fraction, and reduced peripheral resistance. Creatinine clearance and sodium excretion were comparable in patients and controls. Standing induced a decrease in end-diastolic volume in all subjects. Healthy volunteers maintained cardiovascular homeostasis by increasing ejection fraction and heart rate, while both normotensive and hypertensive cirrhotic patients experienced a fall in stroke volume and cardiac index, despite a marked activation of the renin-aldosterone and sympathetic nervous system. Creatinine clearance decreased only in normotensive patients, who experienced the greatest reduction in sodium excretion.

Conclusions: Compensated cirrhotic patients with arterial hypertension had no evidence of hyperdynamic circulation. Like their normotensive counterparts, hypertensive patients had an impaired cardiovascular response to the postural challenge, but a lesser degree of renal dysfunction during standing.

Section snippets

Subjects

The study was performed in 20 healthy volunteers (10 men, mean age (±SD) 60±7, range 47–73 years) and 24 inpatients with compensated cirrhosis and portal hypertension, as indicated by the presence of esophageal varices at endoscopy. Twelve patients (6 males, mean age 58±6, range 47–71 years) had normal arterial pressure, while the remaining 12 (3 males, mean age 62±8, range 49–73 years) had stage 1–2 essential hypertension, according to the VIth report of the Joint National Committee on

Results

The clinical characteristics of the 20 healthy volunteers and 24 cirrhotic patients included in the study are shown in Table 1. UNaV ranged between 90 and 110 mmol/day in all subjects, confirming adherence to the diet. In-hospital systolic and diastolic arterial pressure was: 126±10 over 75±6 mmHg in healthy subjects, 125±13 over 74±7 mmHg in normotensive and 159±13 over 95±7 mmHg in hypertensive cirrhotic patients. A close relationship was found between in-hospital arterial pressure and blood

Cardiac function and systemic hemodynamics

Results of echocardiographic measurements are shown in TABLE 2, TABLE 3. Cirrhotic patients with essential hypertension had the highest LVMI. Relative wall thickness was also higher in this group than in healthy subjects and normotensive cirrhotic patients. In the supine position, normotensive cirrhotic patients had significantly greater CI and lower SVR than healthy subjects and hypertensive cirrhotic patients, no appreciable differences being observed between the latter two groups of subjects

Renal function

No appreciable differences were observed among the three groups of subjects included in the study with respect to supine measurements of creatinine clearance, UNaV and urine flow rate (Table 4). UNaV and urine flow rate decreased during standing in all groups, whereas creatinine clearance decreased only in normotensive cirrhotic patients. Values of urine flow rate observed in hypertensive cirrhotic patients during standing were significantly lower than those of healthy subjects.

Endocrine parameters

Results of endocrine measurements are listed in Table 5. When supine, normotensive cirrhotic patients showed significantly higher plasma ANP levels than healthy subjects and hypertensive patients with cirrhosis. No differences were observed among the three groups of subjects included in the study with respect to the other endocrine parameters measured in the supine position. In the supine position, PAC level significantly correlated with CI (r=0.505, pr=0.35, p=0.029 for SVRI). In cirrhotic

Discussion

When evaluated in the supine position, normotensive patients with compensated cirrhosis had hyperdynamic circulation, as indicated by high cardiac output and reduced SVR. The increased cardiac output was due to both an increased preload and a reduced afterload. In fact, they had a higher LVEDVI, an indicator of left ventricular filling and thus of venous return (20), and also a reduction of the SVI/PP ratio, an approximate measure of arterial compliance 21., 22., pointing to a reduced

Acknowledgements

Supported by grants from the Italian Ministero per l'Università e la Ricerca Scientifica e Tecnologica and the Italian Liver Foundation (1996).

References (28)

G Laffi et al.
Altered cardiovascular responsiveness to active tilting in on-alcoholic cirrhosis
Gastroenterology
(1997)
WH Gaasch
Left ventricular radius to wall thickness ratio
Am J Cardiol
(1979)
M Pozzi et al.
Evidence of functional and structural cardiac abnormalities in cirrhotic patients with and without ascites
Hepatology
(1997)
Z Ma et al.
Cirrhotic cardiomiopathy: getting to the heart of the matter
Hepatology
(1996)
G Laffi et al.
Impaired cardiovascular autonomic response to passive tilting in cirrhosis with ascites
Hepatology
(1996)
HF Loyke
The relationship of cirrhosis of the liver to hypertension: a study of 504 cases of cirrhosis of the liver
Am J Med Sci
(1955)
DT Schwartz
The relation of cirrhosis of the liver to renal hypertension A review of 639 autopsied cases
Ann Intern Med
(1967)
HF Loyke et al.
An evaluation of hypertension and liver disease in an alcoholic service
Am J Med Sci
(1960)
HF Loyke
Reduction of hypertension after liver disease
Arch Intern Med
(1962)
C Lopez et al.
Temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetra-chloride induced cirrhosis
Hepatology
(1991)

F Veglio et al.

Hormonal aspects of the relation of liver cirrhosis to essential hypertension

Clin Exp Hypertens [A]

(1992)

V Arroyo et al.

Ascites, renal failure, and electrolyte disorders in cirrhosis. Pathogenesis, diagnosis, and treatment

P Gentilini et al.

Long course and prognostic factors of virusinduced cirrhosis of the liver

Am J Gastroenterol

(1997)

E Rubin

Alcoholic myopathy in heart and skeletal muscle

N Engl J Med

(1979)

Cited by (40)

Risk of acute coronary syndrome and peripheral arterial disease in chronic liver disease and cirrhosis: A nationwide population-based study
2018, Atherosclerosis
Citation Excerpt :
Therefore, an explanation for our results would be that nonalcoholic fatty liver disease contributes to the increasing risks of ACS and PAD in patients with cirrhosis. Finally, arterial stiffness, meaning a decrease in arterial compliance, is reported in cirrhotic patients [35,36]. Henriksen et al. reported that arterial stiffness in patients with cirrhosis is related to the severity of liver disease [37].
Until now, no study has investigated the risks of acute coronary syndrome (ACS) and peripheral arterial disease (PAD) in cirrhosis.
In this study, 57,214 patients diagnosed with cirrhosis between 2000 and 2010 were identified from the Taiwan National Health Insurance claims data. Each patient was randomly selected and frequency-matched with an individual without cirrhosis by age, sex, and index year.
The overall incidence rates of ACS and PAD were 2.81 and 2.97 per 1000 person-years, respectively, in the cirrhosis cohort. The cirrhosis cohort had a higher risk of ACS [adjusted subhazard ratio (aSHR) = 1.12, 95% confidence interval (CI) = 1.03–1.22] and PAD (aSHR = 1.11, 95% CI = 1.02–1.21). The risk of ACS was highest among members of the cirrhosis cohort with ascites (aSHR = 1.09, 95% CI = 1.11–1.19).
Patients with chronic liver disease and cirrhosis have higher risks of ACS and PAD than those without chronic liver disease and cirrhosis.
Elevated plasma levels of urotensin II do not correlate with systemic haemodynamics in patients with cirrhosis
2011, Digestive and Liver Disease
The hyperdynamic circulation of hepatic cirrhosis is related to decreased systemic vascular resistance due to arterial vasodilation. Urotensin II plasma levels are increased in cirrhotic patients, and have been suggested to play a role in the pathogenesis of systemic haemodynamic alterations.
To evaluate the relationships between systemic haemodynamics and urotensin II plasma levels.
Thirty-six consecutive in-patients with cirrhosis and no alteration of plasma creatinine, and 20 age- and gender-matched healthy volunteers underwent noninvasive assessment of systemic haemodynamics and measurement of urotensin II plasma levels.
In comparison to healthy controls, cirrhotic patients had signs of hyperdynamic circulation and higher plasma urotensin II levels. Plasma urotensin II was neither significantly different amongst patients with different severity of cirrhosis nor between patients with or without ascites. Both in controls and cirrhotic patients no significant correlations were found between parameters of systemic haemodynamics and plasma urotensin II levels.
In patients with cirrhosis and hyperdynamic circulation, but with normal serum creatinine, urotensin II is higher than in healthy subjects. However, no correlation with cardiac index or other haemodynamic parameters was observed, indicating that other mechanisms prevail.
Cirrhotic cardiomyopathy
2010, Journal of the American College of Cardiology
Citation Excerpt :
After the development of ascites, there was more overt evidence of contractile dysfunction despite a decrease in both afterload (arterial vasodilation) and pre-load (venous return) (6). Both hypertensive and normotensive subjects with compensated cirrhosis show a reduction in cardiac index and an increase in systemic vascular resistance (30). These data have been considered to represent underlying “pump dysfunction.”
Cirrhotic cardiomyopathy is a clinical syndrome in patients with liver cirrhosis characterized by an abnormal and blunted response to physiologic, pathologic, or pharmacologic stress but normal to increased cardiac output and contractility at rest. As many as 50% of cirrhotic patients undergoing liver transplantation show signs of cardiac dysfunction, and 7% to 21% of deaths after orthotopic liver transplantation result from overt heart failure. In this review, we critically evaluate the existing literature on the pathophysiology and clinical implications of cirrhotic cardiomyopathy.
Essential hypertension and chronic viral hepatitis
2007, Digestive and Liver Disease
Citation Excerpt :
However, most reports found that the prevalence of arterial hypertension is much lower than expected in patients with cirrhosis [2], and tends to become lower and lower with the progression of liver failure [2,3]. Patients with systemic hypertension and cirrhosis have no evidence of the classical hyperdynamic circulation [4], and also systemic hypotension (<80 mmHg systolic pressure) is considered an independent negative predictor of survival [5]. The liver presents a complex modulation between the local and the systemic circulation, and regulates its own total blood flow by controlling the hepatic artery flow [6].
Both arterial hypertension and chronic hepatitis are common disorders. The relationship between arterial pressure and liver cirrhosis has been extensively studied, but no studies are available in chronic hepatitis (CH). Recently, a few studies have reported that treatment with angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs), commonly used in arterial hypertension, reduce hepatic fibrosis in patients with viral CH and in nonalcoholic steatohepatitis. This study was aimed at comparing the evolution of post-viral CH in patients with/without concomitant essential hypertension.
Two sets of observations were carried out: (a) a cross-sectional cohort study of 95 patients with viral CH, to compare the severity of histological and biochemical data at diagnosis, in relation to pharmacologically treated essential hypertension, and (b) a retrospective study with the observation of 254 patients with CH of viral etiology, followed up from 2 to 20 years, to establish the natural history of viral CH in relation to treated essential hypertension.
In the cross-sectional analysis, patients with treated hypertension had a significantly older age at diagnosis of CH (51.4 ± 8.4 years vs. 46.2 ± 12.2 in normotensive; P < 0.001) and histological evidence of less severe necro-inflammatory liver damage. ALT levels were also lower (109.8 ± 62.5 U/L vs. 166.0 ± 169.5 in normotensive; P < 0.001) as were endothelin-1 levels (0.74 ± 0.97 vs. 1.77 ± 1.51 fmol/mL; P < 0.001). The retrospective study confirmed an older age at diagnosis in patients with treated hypertension (48.7 ± 9.8 vs. 41.9 ± 11.8 years; P < 0.001) and lower death rates (2.2% vs. 11%; P < 0.05).
The evolution of post-viral CH seems to be less severe in subjects with essential hypertension, possibly in relation to treatment with antihypertensive drugs.
Prolonged Q-T<inf>c</inf> interval in mild portal hypertensive cirrhosis
2005, Journal of Hepatology
Citation Excerpt :
Impaired liver function may, in itself, affect the function of the heart, and a cirrhotic cardiomyopathy has been suggested [12–15]. A prolonged Q–T interval, indicating delayed repolarisation of the myocardial cells, has been described in a substantial fraction of patients with cirrhosis [12,16–18]. Investigations of the changes in the ECG indicate that these are independent of aetiology of cirrhosis, but may have a relation to the severity of cirrhosis and portal hypertension [12,16,17,20].
The Q–T_c interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q–T_c interval in cirrhotic patients with hepatic venous pressure gradient (HVPG)<12 mmHg.
Forty-four patients with cirrhosis and HVPG<12 mmHg underwent a haemodynamic study. They were compared with 36 cirrhotic patients with clinically significant portal hypertension (HVPG≥12 mmHg) and controls without liver disease.
The fraction with prolonged Q–T_c interval (>0.440 s^1/2) was similar in the two cirrhotic groups (49 vs 50%, ns) and significantly above that of the controls (5%, P<0.005). Q–T_c was normal in patients with normal HVPG. Likewise, mean Q–T_c was 0.449 and 0.447 s^1/2 in the two cirrhotic groups (ns), values which are significantly above that of the controls (0.410 s^1/2, P<0.01). In the mild portal hypertensive group, the Q–T_c interval was inversely related to indicators of liver function, such as indocyanine green clearance (r=−0.34, P<0.02).
Delayed repolarisation of the myocardium already occurs in a substantial fraction of patients with cirrhosis with only a mild increase in portal pressure. The prolonged Q–T_c interval may be related to liver dysfunction and to the presence of portal hypertension.
Milestones in liver disease: Cardiovascular complications in liver diseases
2003, Journal of Hepatology

View all citing articles on Scopus

View full text

Cardiovascular and renal function in normotensive and hypertensive patients with compensated cirrhosis: effects of posture

Abstract

Section snippets

Subjects

Results

Cardiac function and systemic hemodynamics

Renal function

Endocrine parameters

Discussion

Acknowledgements

Gastroenterology

Am J Cardiol

Hepatology

Hepatology

Hepatology

The relationship of cirrhosis of the liver to hypertension: a study of 504 cases of cirrhosis of the liver

Am J Med Sci

The relation of cirrhosis of the liver to renal hypertension A review of 639 autopsied cases

Ann Intern Med

An evaluation of hypertension and liver disease in an alcoholic service

Am J Med Sci

Reduction of hypertension after liver disease

Arch Intern Med

Temporal relationship between the decrease in arterial pressure and sodium retention in conscious spontaneously hypertensive rats with carbon tetra-chloride induced cirrhosis

Hepatology

Hormonal aspects of the relation of liver cirrhosis to essential hypertension

Clin Exp Hypertens [A]

Ascites, renal failure, and electrolyte disorders in cirrhosis. Pathogenesis, diagnosis, and treatment

Long course and prognostic factors of virusinduced cirrhosis of the liver

Am J Gastroenterol

Alcoholic myopathy in heart and skeletal muscle

N Engl J Med