The purpose of research - to study the features of circadian profile of blood pressure (BP), the data of echocardiography, pH-monitoring, lipid spectrum, level of apelin and the state of the system "lipid peroxidation-antioxidant protection" in patients with a combination of arterial hypertension (AH) and gastroesophageal reflux disease (GERD) depending on the level of AH. It was examined 126 patients with combination of AH II stage, 2-3 degrees, and GERD, 70 (55.56%) men and 56 (44.44%) women, mean age 56.84 ± 1.17. The anthropometric indicators, a condition of "lipid peroxidation- antioxidant protection", the level of apelin, ambulatory blood pressure monitoring (ABPM), echocardiography, esophageal pH-monitoring were evaluated. Analysis of the results was performed using a computer program IBM SPSS Statistics 21.0 for Windows XP. According to the daily averages ABPM systolic BP/diastolic BP in the I group were 141.2 ± 0.8/90.4 ± 0.4 mm Hg., in II group - 163.3 ± 0.9/101.0 ± 0.5 mm Hg., in III group - 185.6 ± 0.8/112.1 ± 0.5 mm Hg., p = 0.001. There are only 25.39% of patients had normal indicators of the variability of BP among individuals with comorbidity. Transformation from mild AH to moderate was accompanied by a significant increase in the severity of left ventricular remodeling by type of concentric hypertrophy. The data of esophageal pH-monitoring allow us to classify the disorders as severe gastroesophageal reflux in patients with a combination of AH and GERD (DeMeester, 1993). In the group with first degree of AH the average rate of circulating apelin was 930.58 ± 56.27 pg/mL, for the patients with 2nd degree of AH - 880.56 ± 17.97 pg/ml, p>0.05, in patients with third degree of AH - 650.91 ± 12.87 pg/ml (p = 0.001). Assessment of lipid profile has allowed to establish the worse dyslipidemia in patients with 3rd degree of AH combined with GERD (atherogenic ratio - 3.11 ± 0.09). The deterioration of degree of AH combined with GERD accompanied by an increase of oxidative stress with increase of nitrites plasma and malondialdehyde concentration, and decrease of glutathione peroxidase and of SH-groups concentration. Increased degree of AH in patients with severe GERD accompanied by worsening of left ventricular remodeling, reduction of apelin levels, progression of dyslipidemia, and imbalances in the system of "lipid peroxidation-antioxidant protection."
BACKGROUND: The National Health and Morbidity Survey in 2011 estimated that 35.1% (5.7 million) of Malaysian adults aged 18 and older suffer from hypertension. Hypertension is still treated by conventional medicine despite its exact aetiology being unknown. Studies showed that oxidative stress and low availability of nitric oxide (NO) causes an increase in vascular wall tension and increase blood pressure. Piper sarmentosum (PS) a traditional Malay herbal plant is well known for its high antioxidant content. Antioxidant is useful in improving cardiovascular diseases particularly hypertension. Thus, it is beneficial to determine the effect of PS leaves aqueous extract (Kadukmy™) on the blood pressure, NO level, oxidative stress markers and serum cholesterol level of the Spontaneous Hypertensive Rats (SHR).
METHODS: Rats were devided into five groups consisting of three treatment groups and two control groups. Baseline blood investigations were done before and following commencement of treatment. Spontaneous hypertensive rats were treated for 28 consecutive days and the blood pressure was measured weekly.
RESULTS: Kadukmy™ administration showed a significant reduction in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) (P blood pressure and cholesterol level.
Hypoadiponectinemia is characterized by low plasma adiponectin levels that can be caused by genetic factors, such as single nucleotide polymorphisms (SNPs) and mutations in the adiponectin gene or by visceral fat deposition/obesity. Reports have suggested that hypoadiponectinemia is associated with dyslipidemia, hypertension, hyperuricemia, metabolic syndrome, atherosclerosis, type 2 diabetes mellitus and various cardiovascular diseases. Previous studies have highlighted several potential strategies to up-regulate adiponectin secretion and function, including visceral fat reduction through diet therapy and exercise, administration of exogenous adiponectin, treatment with peroxisome proliferator-activating receptor gamma (PPARγ) agonists (e.g., thiazolidinediones (TZDs)) and ligands (e.g., bezafibrate and fenofibrate) or the blocking of the renin-angiotensin system. Likewise, the up-regulation of the expression and stimulation of adiponectin receptors by using adiponectin receptor agonists would be an effective method to treat obesity-related conditions. Notably, adiponectin is an abundantly expressed bioactive protein that also exhibits a wide spectrum of biological properties, such as insulin-sensitizing, anti-diabetic, anti-inflammatory and anti-atherosclerotic activities. Although targeting adiponectin and its receptors has been useful for treating diabetes and other metabolic-related diseases in experimental studies, current drug development based on adiponectin/adiponectin receptors for clinical applications is scarce, and there is a lack of available clinical trial data. This comprehensive review discusses the strategies that are presently being pursued to harness the potential of adiponectin up-regulation. In addition, we examined the current status of drug development and its potential for clinical applications.
Probiotics are live organisms that are primarily used to improve gastrointestinal disorders such as diarrhea, irritable bowel syndrome, constipation, lactose intolerance, and to inhibit the excessive proliferation of pathogenic intestinal bacteria. However, recent studies have suggested that probiotics could have beneficial effects beyond gastrointestinal health, as they were found to improve certain metabolic disorders such as hypertension. Hypertension is caused by various factors and the predominant causes include an increase in cholesterol levels, incidence of diabetes, inconsistent modulation of renin and imbalanced sexual hormones. This review discusses the antihypertensive roles of probiotics via the improvement and/or treatment of lipid profiles, modulation of insulin resistance and sensitivity, the modulation of renin levels and also the conversion of bioactive phytoestrogens as an alternative replacement of sexual hormones such as estrogen and progesterone.
Irregular atrial pressure, defective folate and cholesterol metabolism contribute to the pathogenesis of hypertension. However, little is known about the combined roles of the methylenetetrahydrofolate reductase (MTHFR), apolipoprotein-E (ApoE) and angiotensin-converting enzyme (ACE) genes, which are involved in metabolism and homeostasis. The objective of this study is to investigate the association of the MTHFR 677 C>T and 1298A>C, ACE insertion-deletion (I/D) and ApoE genetic polymorphisms with hypertension and to further explore the epistasis interactions that are involved in these mechanisms. A total of 594 subjects, including 348 normotensive and 246 hypertensive ischemic stroke subjects were recruited. The MTHFR 677 C>T and 1298A>C, ACE I/D and ApoEpolymorphisms were genotyped and the epistasis interaction were analyzed. The MTHFR 677 C>T and ApoE polymorphisms demonstrated significant associations with susceptibility to hypertension in multiple logistic regression models, multifactor dimensionality reduction and a classification and regression tree. In addition, the logistic regression model demonstrated that significant interactions between the ApoE E3E3, E2E4, E2E2 and MTHFR 677 C>T polymorphisms existed. In conclusion, the results of this epistasis study indicated significant association between the ApoE and MTHFR polymorphisms and hypertension.
Serum concentrations and urinary output of calcium, magnesium, sodium and potassium were analysed in normotensive pregnant women and in women with pregnancy-induced hypertension during the third trimester. In addition, plasma renin activity (PRA) was also determined. Significantly lower serum total calcium, urinary calcium and magnesium excretions and plasma renin activity were evident in women with PIH. Urine output and creatinine clearance were not significantly different between the two groups. No significant correlation was evident between serum calcium, magnesium and PRA. The relationship between these parameters and high blood pressure is not immediately apparent. They nevertheless suggest of a disturbance in electrolyte metabolism in women with PIH, that may underly the pathogenesis of this disorder.
Recent studies using the ratio of plasma aldosterone concentration (PAC) to PRA as the screening test for primary aldosteronism in hypertensive populations suggested that the prevalence may be as high as 5-15%, with well over half of the subjects having normal serum potassium concentrations. Despite an increasing clinical awareness of this entity, many clinicians are reluctant to consider routine screening for primary aldosteronism in essential hypertensive patients because there are few community-based prevalence studies of primary aldosteronism in different populations. Furthermore, genetic and environmental differences may affect the prevalence and presentation of primary aldosteronism in distinct populations. This study was designed to determine the prevalence of primary aldosteronism in the predominantly Chinese population in Singapore. Three hundred and fifty unselected adult hypertensive patients attending two primary care clinics had random ambulatory measurements for PAC (nanograms per dL) and PRA (nanograms per mL/h). Serum urea, creatinine, and electrolyte measurements were obtained simultaneously. Subjects with renal insufficiency (serum creatinine, >140 micromol/L) and those treated with glucocorticoids or spironolactone were excluded. Screening was considered positive if the PAC: PRA ratio was more than 20 and the PAC was more than 15 ng/dL (>416 pmol/L). Primary aldosteronism was confirmed with the determination of PAC after 2 L saline administered iv over 4 h. Adrenal computed tomographic (CT) scans were performed in biochemically confirmed cases of primary aldosteronism. Further localization with adrenal vein sampling was carried out in selected patients with equivocal findings on adrenal CT scan. Sixty-three (18%) of the 350 hypertensive patients (215 women and 135 men; age range, 23-75 yr) were screened positive for primary aldosteronism. Only 13 of these 63 subjects (21%) were hypokalemic (serum potassium, <3.5 mmol/L). Confirmatory studies were carried out in 56 (89%) of the subjects with a positive PAC:PRA ratio. Using a PAC above 10 ng/dL (>277 pmol/L) after saline infusion as the diagnostic cut-off, 16 of the 56 patients had biochemically confirmed primary aldosteronism. Hypokalemia was found in 6 of the 16 patients (37.5%) with primary aldosteronism. Subtype evaluation with adrenal CT scan and adrenal vein sampling indicated that half of the patients with primary aldosteronism may have had potentially curable unilateral adrenal adenoma. Our data suggest that primary aldosteronism occurs in at least 5% of the adult Asian hypertensive population, and approximately half of these individuals may have potentially curable, unilateral, aldosterone-producing adrenal adenoma. Our findings also confirm the poor predictive value of hypokalemia in both the diagnosis and the exclusion of primary aldosteronism.
To compare homocysteine (Hcy) concentration in the blood plasma, vitreous and aqueous of eyes with proliferative diabetic retinopathy (PDR) against control, and to investigate associations between Hcy concentration in blood plasma with that of aqueous and vitreous in these two groups.
Parkia speciosa Hassk is a plant found abundantly in Southeast Asia region. Its seeds with or without pods and roots have been used in traditional medicine in this region to treat hypertension. Therefore, we aimed to investigate the potential effect of the plant empty pod extract on hypertension development and changes in heart induced by N(G)-nitro-l-arginine methyl ester (l-NAME) administration in rats. Twenty-four male Sprague Dawley rats were divided into four groups. Groups 1 to 3 were given l-NAME (25mg/kg, intraperitoneally) for 8 weeks. Groups 2 and 3 were also given Parkia speciosa empty pods methanolic extract (800mg/kg, orally) and nicardipine (3mg/kg, orally), concurrently with l-NAME. The last group served as the control. l-NAME reduced plasma nitric oxide level and therefore, increased systolic blood pressure, angiotensin-converting enzyme and NADPH oxidase activities as well as lipid peroxidation in the heart. Parkia speciosa extract and nicardipine treatments had significantly prevented the elevations of blood pressure, angiotensin-converting enzyme, NADPH oxidase activities and lipid peroxidation in the heart induced by the l-NAME. Parkia speciosa extract but not nicardipine prevented the reduction in plasma nitric oxide level caused by l-NAME. In conclusion, Parkia speciosa empty pods methanolic extract has a potential to prevent the development of hypertension possibly by preventing the loss of plasma nitric oxide, as well as has cardioprotective effects by reducing angiotensin-converting enzyme activity and oxidative stress in the heart in rats administered l-NAME.
The aim of research was to investigate the plasma microRNA (miR-133а) level in patients with essential arterial hypertension (EAH). A total of 45 patients with EAH 2-3 degrees aged 52.14 ± 8.25 years and 21 healthy individuals (control group) with comparable age and sex distributions. The following frequency of risk factors was revealed among the examined patients: overweight (53%), dyslipidaemia (73%), pre-diabetes (13%), asymptomatic hyperuricemia (29%); hypertension-mediated organ damage: increased arterial stiffness (27%), left ventricular hypertrophy (55%), atherosclerotic plaque in the carotid artery (40%), microalbuminuria (15%), moderate stage of chronic kidney disease (22%) and cardiovascular diseases: stable ischemic heart disease (11%) and heart failure with preserved ejection fraction of NYHA functional class I (18%). The plasma miR-133a level was determined by polymerase chain reaction using "CFX96 Touch" detection system (BioRad) and "TaqMan microRNA Assay" and "TaqMan® Universal PCR Master Mix" reagents (Thermo Fisher Scientific, USA). It has been established that in patients with EAH the plasma level of miR-133a was significantly lower than in practically healthy individuals (0,182 [0,102; 0,301] ), vs (0,382 [0,198; 0,474]), p <0.05). It has also been revealed a significant decrease in the level of miR-133a in the blood plasma in patients with such organs damage as LVH (0,133 [0,099;0,184]) in comparison with patients without LVH (0,238 [0,155; 0,410]), p <0.05) and also significantly lower than in healthy subjects in the control group (0,382 [0,198; 0,474]), p<0.05). There were no statistically significant differences in the plasma levels of miR-133a in the group of patients with EAH, depending on the presence of risk factors, other organ damage and cardiovascular diseases. The findings suggest the significant role of reducing of plasma levels of miR-133a in the pathogenesis of hypertension itself and in pathological remodeling of the heart.
Hypertension is a common but complex human disease, which can lead to a heart attack, stroke, kidney disease or other complications. Since the pathogenesis of hypertension is heterogeneous and multifactorial, it is crucial to establish a comprehensive metabolomic approach to elucidate the molecular mechanism of hypertension. Although there have been limited metabolomic, lipidomic and pharmacometabolomic studies investigating this disease to date, metabolomic studies on hypertension have provided greater insights into the identification of disease-specific biomarkers, predicting treatment outcome and monitor drug safety and efficacy. Therefore, we discuss recent updates on the applications of metabolomics technology in human hypertension with a focus on metabolic biomarker discovery.
Mortality from ischaemic heart disease in Singapore is now reaching comparability with the West. For the early 1980s, rates for Indians and Malays were higher than in U.S.A. and England and Wales and while those for Chinese were lower they were considerably higher than in Japan. In keeping with this the levels of the major risk factors in Singapore are now comparable to the West. Cigarette smoking in males is virtually the same as in Britain, while the proportion of hypertensives on medication is higher than in the West. The main cause for concern is the current high levels of serum cholesterol in Singapore and strenuous health education efforts are needed to bring about dietary changes.
Introduction Testosterone plays an important role in the blood pressure regulation. However, information with regard to the effect of this hormone on blood pressure in normotensive and hypertensive conditions is limited. Therefore, in this study, the relationship between plasma testosterone level and mean arterial pressure (MAP) was investigated under these conditions. Methods Normotensive Wistar-Kyoto (WKY) and hypertensive Spontaneous Hypertensive (SHR) male and female rats were gonadectomized with female rats treated with testosterone. Estrous cycle stages of intact female rats of both strains were identified by vaginal smear. Pressure in the carotid artery of anesthetized rats was measured via direct cannulation technique. The blood was withdrawn for plasma testosterone level measurement by enzyme-linked immunosorbent assay. Results Treatment of ovariectomized female WKY and SHR rats with testosterone for 6-week duration has resulted in MAP to increase (P blood pressure to increase.
BACKGROUND:Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke.
METHODS:We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals.
FINDINGS: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001).
INTERPRETATION: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke.
FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.
The prolonged intake of diet containing repeatedly heated vegetable oil can cause hypertension in the long run. In this study, the effects of citrus leaf extract (CLE) supplementation on vascular reactivity, plasma nitrite, and aortic structure in hypertensive rats were investigated by the consumption of repeatedly heated vegetable oil [corrected]. Male Sprague Dawley rats (n = 56) were divided into 7 groups corresponding to the respective diets. For 16 weeks, 1 group was given standard rat chow (control) while other groups were given diets containing 15% w/w of palm oil, fresh palm oil (FPO), palm oil heated 5 times (5HPO), and palm oil heated 10 times (10HPO), with or without the incorporation of 0.15% w/w CLE (FPO+CLE, 5HPO+CLE, or 10HPO+CLE). Plasma nitrite levels were measured before and at 16 weeks of treatment. After 16 weeks, the rats were sacrificed and aortae were harvested for measuring vascular reactivity and for microscopic study. CLE supplementation had significantly reduced the loss of plasma nitrite and attenuated the vasoconstriction response to phenylephrine in the 5HPO group but not in the 10HPO group. However, CLE had no significant effect on the vasorelaxation response to acetylcholine and sodium nitroprusside. The elastic lamellae of tunica media in 5HPO, 10HPO, and 10HPO+CLE groups appeared disorganised and disrupted. Obtained findings suggested that CLE was able to enhance nitric oxide bioavailability that might dampen the vasoconstriction effect of phenylephrine.
Obesity is well associated as being an interfering factor in metabolic diseases such as hypertension and diabetes by increasing the secretion of proinflammatory markers from adipose tissue. Having healthy effects, vitamin C could work as an anti-inflammatory agent through its antioxidant capacity.
The aim of this study was to determine the effects of gamma tocotrienol on lipid peroxidation and total antioxidant status of spontaneously hypertensive rats (SHR), comparing them with normal Wistar Kyoto (WKY) rats. SHR were divided into three groups and treated with different doses of gamma tocotrienol (gamma1, 15 mg/kg diet; gamma2, 30 mg/kg diet and gamma3, 150 mg/kg diet). Normal WKY and untreated SHR were used as normal (N) and hypertensive control (HC). Blood pressure were recorded every fortnightly for three months. At the end of the trial, animals were killed and measurement of plasma total antioxidant status, plasma superoxide dismutase (SOD) activity and lipid peroxide levels in plasma and blood vessels were carried out following well established methods. Study shows that lipid peroxides were significantly higher in hypertensive plasma and blood vessels compared to that of normal rats (Plasma- N: 0.06+/-0.01, HC: 0.13+/-0.008; p<0.001, B1. Vessels - N: 0.47+/-0.17, HC: 0.96+/-0.37; p<0.001). SOD activity was significantly lower in hypertensive than normal rats (N = 148.58+/-29.56 U/ml, HC = 110.08+/-14.36 U/ml; p = 0.014). After three months of antioxidant trial with gamma-tocotrienol, it was found that all the treated groups have reduced plasma lipid peroxides concentration but was only significant for group gamma1 (gamma1: 0.109+/-0.026, HC: 0.132+/-0.008; p = 0.034). On the other hand, lipid peroxides in blood vessels reduced significantly in all treated groups (gamma1; p<0.05, gamma2; p<0.001, gamma3; p<0.005). All the three treated groups showed improve total antioxidant status (p<0.001) significantly. SOD activity also showed significant improvement in all groups (gamma1: p<0.001, gamma2: p<0.05, gamma3: p<0.001). Correlation studies showed that, total antioxidant status (TAS) and SOD were significantly negatively correlated with blood pressure in normal rats (p = 0.007; p = 0.008) but not in SHR control. This correlation regained in all three groups SHR's after treatment with tocotrienol. Lipid peroxides in blood vessel and plasma showed a positive correlation with blood pressure in normal and SHR control. This correlation also remains in treated groups significantly except that in gamma3 where positive correlation with plasma lipid peroxide was not significant. In conclusion it was found that antioxidant supplement of gamma-tocotrienol may prevent development of increased blood pressure, reduce lipid peroxides in plasma and blood vessels and enhanced total antioxidant status including SOD activity.
We investigated the total urinary kallikrein levels, left-ventricular wall thickness and mean arterial blood pressure of nontreated and captopril-treated diabetic and nondiabetic spontaneously hypertensive rats. The mean arterial blood pressure was significantly elevated in diabetic spontaneously hypertensive rats as compared to nondiabetic spontaneously hypertensive rats. Captopril treatment caused a significant reduction in the arterial blood pressure of both nondiabetic and diabetic spontaneously hypertensive rats. The left-ventricular wall thickness was also significantly reduced in diabetic and nondiabetic spontaneously hypertensive treated with captopril as compared to nontreated diabetic and nondiabetic spontaneously hypertensive rats. The total urinary kallikrein levels were significantly raised in captopril-treated diabetic and nondiabetic spontaneously hypertensive rats against the values obtained from nontreated diabetic and nondiabetic spontaneously hypertensive rats. These results indicate that blood pressure reduction and left ventricular wall regression with captopril treatment might be due to enhanced renal kallikrein formation. The significance of these findings is discussed.
Twenty eight patients who satisfied the entry criteria and had completed an initial 2 weeks treatment with placebo were titrated fortnightly with doses of Nicardipine ranging from 30 mg to 90 mg daily in two or three divided doses. Nicardipine treatment significantly reduced blood pressures both in the supine and standing positions (p < 0.0004) when compared with placebo treatment. Heart rates however did not change significantly. Forty six percent (13/28) of patients on 20 mg twice daily, 25% (7/28) on 10 mg three times daily, 18% (5/28) of patients on 20 mg three times daily and 11% (3/28) on 30 mg three times daily achieved supine diastolic blood pressures < 90 mm Hg. Nicardipine treatment at 16 weeks and at 24 weeks did not significantly alter the lipid profile when compared to the end of placebo treatment period. No other biochemical abnormalities were reported during the study period. Except for 2 cases of mild pedal oedema and 2 cases of transient headaches, no serious side-effects were encountered.