Vasilios Kotsis

Mechanisms of obesity-induced hypertension

The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle of infinite feedback gain, seems to be shifted toward higher blood-pressure levels in obese individuals. During the early phases of obesity, primary sodium retention exists as a result of increase in renal tubular reabsorption. Extracellular-fluid volume is expanded and the kidney-fluid apparatus is resetted to a hypertensive level, consistent with a model of hypertension because of volume overload. Plasma renin activity, angiotensinogen, angiotensin II and aldosterone values display significant increase during obesity. Insulin resistance and inflammation may promote an altered profile of vascular function and consequently hypertension. Leptin and other neuropeptides are possible links between obesity and the development of hypertension. Obesity should be considered as a chronic medical condition, which is likely to require long-term treatment. Understanding of the mechanisms associated with obesity-related hypertension is essential for successful treatment strategies.

Impact of Obesity on 24-Hour Ambulatory Blood Pressure and Hypertension

The purpose of the present study was to determine the relationship between body mass index (BMI) and parameters derived from 24-hour ambulatory blood pressure monitoring including mean 24-hour daytime and nighttime systolic and diastolic blood pressures, 24-hour daytime and nighttime pulse pressure, mean 24-hour daytime and nighttime heart rate, dipping and nondipping status. 3216 outpatient subjects who visited our hypertension center and were never treated with antihypertensive medication underwent 24-hour blood pressure monitoring. BMI was significantly correlated with clinic systolic and diastolic blood pressures. Significant correlations were also found between BMI and mean 24-hour daytime and nighttime systolic blood pressure, 24-hour daytime and nighttime pulse pressure, and mean 24-hour daytime and nighttime heart rate. In multivariate regression analysis, clinic systolic, diastolic blood pressure, mean 24-hour systolic blood pressure, 24-hour pulse pressure, and high-density lipoprotein were independently correlated with BMI. The incidence of white coat hypertension was higher in overweight and obese patients than in normal weight subjects. Confirmed ambulatory blood pressure hypertension was also found to be higher in overweight and obese individuals compared with normal weight subjects. Our data also highlight the higher incidence of nondipping status in obesity. These findings suggest that obese patients had increased ambulatory blood pressure parameters and altered circadian blood pressure rhythm with increased prevalence of nondipping status.

Target Organ Damage in “White Coat Hypertension” and “Masked Hypertension”

BACKGROUND In this study we investigated (i) the prevalence of white coat hypertension (WCH) and masked hypertension (MH) in patients who had never been treated earlier with antihypertensive medication, and (ii) the association of these conditions with target organ damage. METHODS A total of 1,535 consecutive patients underwent office blood pressure (BP) measurements, 24-h ambulatory BP monitoring (ABPM), echocardiography, and ultrasonography of the carotid arteries. Subjects who showed normotension or hypertension on the basis of both office and ambulatory BP (ABP) measurement were characterized as having confirmed normotension or confirmed hypertension, respectively. WCH was defined as office hypertension with ambulatory normotension, and MH as office normotension with ambulatory hypertension. RESULTS WCH was found in 17.9% and MH in 14.5% of the subjects. The prevalence of WCH was significantly higher in subjects with obesity, while the prevalence of MH was significantly higher in normal-weight subjects. The confirmed hypertensive subjects as well as the masked hypertensive subjects had significantly higher left ventricular mass (LVM) (corrected for body surface area) and carotid intima media thickness (cIMT) than the confirmed normotensive subjects did (108.9 +/- 30.6, 107.1 +/- 29.1 vs. 101.4 +/- 29.9 g/m(2) and 0.68 +/- 0.16, 0.68 +/- 0.21 vs. 0.63 +/- 0.15 mm, respectively, P < 0.005). White coat hypertensive subjects did not have a significantly higher LVM index than confirmed normotensive subjects (101.5 +/- 25.9 vs. 101.4 +/- 29.9 g/m(2)); they tended to have higher cIMT than the confirmed normotensive subjects, but the difference was not statistically significant (0.67 +/- 0.15 vs. 0.63 +/- 0.15 mm). CONCLUSIONS WCH and MH are common conditions in patients who visit hypertension outpatient clinics. Confirmed hypertension and MH are accompanied by increased LVM index and cIMT, even after adjusting for other risk factors.

Early vascular ageing in translation: from laboratory investigations to clinical applications in cardiovascular prevention

The ageing of the vascular tree is a fundamental reflection of biological ageing in general and a determinant of organ function. In the arterial wall this is characterized by a reduction in the elastin content, as well as by an increased content of collagen and its cross-linkages, leading to increased arterial stiffness and elevated central as well as brachial blood pressure, accompanied by increased SBP variability. In recent years a better understanding of these processes have led to the proposal of a condition named early vascular ageing (EVA) in patients with increased arterial stiffness for their age and sex. This is a condition that could increase cardiovascular risk and is associated with various degrees of cognitive dysfunction, as well as other features of biological ageing. This brief review aims to give an update on EVA and how the concept can be used in clinical practice.

Impact of obesity in intima media thickness of carotid arteries

Objective: To explore differences in intima media thickness (IMT) of the carotid arteries induced by differences in BMI.

Early vascular aging and the role of central blood pressure

Vascular aging is described as a gradual process involving biochemical, enzymatic, and cellular changes of the vasculature and modification of the signals that modulate them. On the basis of this conception a new pathophysiological model for deeper understanding of cardiovascular risk and its treatment was introduced. The idea of early vascular aging, that is the acceleration of vascular aging seems to be a promising tool for clinical guidance in individuals at increased cardiovascular risk or a strong family history of early cardiovascular manifestations. Increased arterial stiffness, dilation of central elastic arteries, impaired endothelial function and vasodilatation are dominant aspects of this premature process.

Arterial stiffness and 24 h ambulatory blood pressure monitoring in young healthy volunteers: The early vascular ageing Aristotle University Thessaloniki Study (EVA-ARIS Study)

Differences in 24 h blood pressure (BP) monitoring parameters such as average 24 h BP, day to night BP ratio and BP variability could have an impact in arterial stiffness. The study hypothesis was that despite similar average BP values in ambulatory blood pressure monitoring subjects with increased 24 h BP variability may have increased arterial stiffness. The study population consisted of 115 consecutive young healthy volunteers. Carotid-femoral PWV was measured in all subjects. Clinic BP was measured and an appropriate cuff was fitted on the non-dominant arm of each subject for a 24 h ambulatory blood pressure monitoring session. Waist to hip ratio as well as BMI was measured. Family history and smoking habits were recorded. In univariate analysis, estimated carotid-femoral PWV showed a significant correlation with age, weight, waist circumference, height, clinic systolic and diastolic BP, 24-h systolic and diastolic BP, 24-h pulse pressure, 24-h systolic and diastolic BP variability, daytime systolic and diastolic BP, daytime pulse pressure, daytime systolic and diastolic BP variability, nighttime systolic BP, nighttime pulse pressure and nighttime systolic BP variability. In multivariate regression analysis, age (B=0.95, P<0.001) and 24 h systolic BP variability (B=0.28, P<0.001) were independent determinanats of arterial stiffness. In conclusions, increased 24 h systolic BP variability is associated with arterial stiffness in young healthy volunteers. Pulse wave velocity in a young healthy population is useful to identify determinants of premature arterial stiffness, thus further elucidating the aspects of early vascular ageing.

Reproducibility of ambulatory blood pressure measurements in essential hypertension.

Background Data on the reproducibility of serial measurements of ambulatory blood pressure in hypertensive patients are lacking. The purpose of this study was to examine (1) the reproducibility of four consecutive ambulatory blood pressure measurements, and (2) the reproducibility of nocturnal falls in blood pressure in hypertensive patients. Methods Twenty patients with mild to moderate essential hypertension underwent four separate ambulatory blood pressure monitorings, on the same day of the week, at 30‐day intervals. Antihypertensive therapy was discontinued for 2 weeks before each recording. Comparing the mean values of blood pressure over 24 h, as well as diurnal, nocturnal and hourly periods, among the four recordings determined the reproducibility of blood pressure measurements. A day/night difference in mean systolic and in mean diastolic blood pressure defined the nocturnal fall in blood pressure. Results No significant differences were observed in either hourly, 24‐h, diurnal or nocturnal systolic blood pressure, diastolic blood pressure and heart rate, or in the nocturnal fall in systolic and diastolic blood pressure among the four recordings. Conclusions Hourly systolic blood pressure, diastolic blood pressure, heart rate, and nocturnal fall in blood pressure were reproducible in four ambulatory blood pressure monitorings recorded over 4 months. These findings suggest that ambulatory blood pressure monitoring is a reliable tool to monitor blood pressure changes.

The use of statins alone, or in combination with pioglitazone and other drugs, for the treatment of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and related cardiovascular risk. An Expert Panel Statement

Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is characterized by accumulation of fat (>5% of the liver tissue), in the absence of alcohol abuse or other chronic liver diseases. It is closely related to the epidemic of obesity, metabolic syndrome or type 2 diabetes mellitus (T2DM). NAFLD can cause liver inflammation and progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis or hepatocellular cancer (HCC). Nevertheless, cardiovascular disease (CVD) is the most common cause of death in NAFLD/NASH patients. Current guidelines suggest the use of pioglitazone both in patients with T2DM and in those without. The use of statins, though considered safe by the guidelines, have very limited use; only 10% in high CVD risk patients are on statins by tertiary centers in the US. There are data from several animal studies, 5 post hoc analyses of prospective long-term survival studies, and 5 rather small biopsy proven NASH studies, one at baseline and on at the end of the study. All these studies provide data for biochemical and histological improvement of NAFLD/NASH with statins and in the clinical studies large reductions in CVD events in comparison with those also on statins and normal liver. Ezetimibe was also reported to improve NAFLD. Drugs currently in clinical trials seem to have potential for slowing down the evolution of NAFLD and for reducing liver- and CVD-related morbidity and mortality, but it will take time before they are ready to be used in everyday clinical practice. The suggestion of this Expert Panel is that, pending forthcoming randomized clinical trials, physicians should consider using a PPARgamma agonist, such as pioglitazone, or, statin use in those with NAFLD/NASH at high CVD or HCC risk, alone and/or preferably in combination with each other or with ezetimibe, for the primary or secondary prevention of CVD, and the avoidance of cirrhosis, liver transplantation or HCC, bearing in mind that CVD is the main cause of death in NAFLD/NASH patients.

Pregnancy-Induced hypertension.

Pregnancy-induced hypertension (PIH) complicates 6–10% of pregnancies. It is defined as systolic blood pressure (SBP) >140 mmHg and diastolic blood pressure (DBP) >90 mmHg. It is classified as mild (SBP 140–149 and DBP 90–99 mmHg), moderate (SBP 150–159 and DBP 100–109 mmHg) and severe (SBP ≥160 and DBP ≥110 mmHg). PIH refers to one of four conditions: a) pre-existing hypertension, b) gestational hypertension and preeclampsia (PE), c) pre-existing hypertension plus superimposed gestational hypertension with proteinuria and d) unclassifiable hypertension. PIH is a major cause of maternal, fetal and newborn morbidity and mortality. Women with PIH are at a greater risk of abruptio placentae, cerebrovascular events, organ failure and disseminated intravascular coagulation. Fetuses of these mothers are at greater risk of intrauterine growth retardation, prematurity and intrauterine death. Ambulatory blood pressure monitoring over a period of 24 h seems to have a role in predicting deterioration from gestational hypertension to PE. Antiplatelet drugs have moderate benefits when used for prevention of PE. Treatment of PIH depends on blood pressure levels, gestational age, presence of symptoms and associated risk factors. Non-drug management is recommended when SBP ranges between 140–149 mmHg or DBP between 90–99 mmHg. Blood pressure thresholds for drug management in pregnancy vary between different health organizations. According to 2013 ESH/ESC guidelines, antihypertensive treatment is recommended in pregnancy when blood pressure levels are ≥150/95 mmHg. Initiation of antihypertensive treatment at values ≥140/90 mmHg is recommended in women with a) gestational hypertension, with or without proteinuria, b) pre-existing hypertension with the superimposition of gestational hypertension or c) hypertension with asymptomatic organ damage or symptoms at any time during pregnancy. Methyldopa is the drug of choice in pregnancy. Atenolol and metoprolol appear to be safe and effective in late pregnancy, while labetalol has an efficacy comparable to methyldopa. Angiotensin-Converting enzyme (ACE) inhibitors and angiotensin II antagonists are contraindicated in pregnancy due to their association with increased risk of fetopathy.