Abdul Rashid Abdul Rahman

Hypertension and stroke in Asia: prevalence, control and strategies in developing countries for prevention

Reliable statistics related to the prevalence, incidence and mortality of hypertension and stroke are not available from Asia. The data may be in national or institutional reports or journals published in the local language only. The mortality rate for stroke has been on the decline since the mid 1960s in the developed countries of Asia, such as Australia, New Zealand, and Japan, with some improvement in Singapore, Taiwan and Hong Kong, some areas of China and Malaysia about 15 years later. In India, China, Phillippines, Thailand, Sri Lanka, Iran, Pakistan, Nepal, there has been a rapid increase in stroke mortality and prevalence of hypertension. The prevalence of hypertension according to new criteria (>140/90 mm Hg) varies between 15–35% in urban adult populations of Asia. In rural populations, the prevalence is two to three times lower than in urban subjects. Hypertension and stroke occur at a relatively younger age in Asians and the risk of hypertension increases at lower levels of body mass index of 23–25 kg/m2. Overweight, sedentary behaviour, alcohol, higher social class, salt intake, diabetes mellitus and smoking are risk factors for hypertension in most of the countries of Asia. In Australia, New Zealand and Japan, lower social class is a risk factor for hypertension and stroke. Population-based long-term follow-up studies are urgently needed to demonstrate the association of risk factors with hypertension in Asia. However prevention programmes should be started based on cross-sectional surveys and case studies without waiting for the cohort studies.

Effect of angiotensin II on pulse wave velocity in humans is mediated through angiotensin II type 1 (AT(1)) receptors.

The objective of this study was to examine the effect of angiotensin II (Ang II) and angiotensin II type 1 (AT1) receptor blockade on pulse wave velocity (PWV) in healthy humans. We studied nine young male volunteers in a double-blind randomised crossover design. Carotid-femoral PWV (an index of arterial stiffness) was measured by using a Complior® machine. Subjects were previously treated for 3 days with once-daily dose of either a placebo or valsartan 80 mg. On the third day, they were infused with either placebo or 5 ng/kg/min of Ang II over 30 min. Subjects thus received placebo capsule + placebo infusion (P), valsartan + placebo infusion (V), placebo + Ang II infusion (A), and valsartan + Ang II infusion (VA) combinations. Heart rate (HR), blood pressure and PWV were recorded at baseline and then every 10 min during infusion and once after the end of infusion. There were significant increases in systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) with A compared with P (P = 0.002, P = 0.002, P = 0.001 respectively). These rises in blood pressure were completely blocked by valsartan. A significant rise in PWV by A was seen compared with P (8.38 ± 0.24 vs 7.48 ± 0.24 m/sec, P = 0.013) and was completely blocked by valsartan; VA compared with P (7.27 ± 0.24 vs 7.48 ± 0.24 m/sec, P = NS). Multiple linear regression analysis showed that blockade of Ang II induced increase in blood pressure by valsartan contributed to only 30% of the total reduction in Ang II induced rise in PWV (R2 = 0.306). The conclusions were that valsartan completely blocks the effect of Ang II on PWV. The effect of Ang II on PWV is mediated through AT1receptors. Reduction in PWV by Ang II antagonist is not fully explained by its pressure lowering effect of Ang II and may be partially independent of its effect on blood pressure.

Identification of psychosocial factors of noncompliance in hypertensive patients

This cross-sectional study was aimed to identify the predictors of medication noncompliance in hypertensive patients. The study was conducted at the Family Medicine Clinic, Hospital Universiti Sains Malaysia, Kelantan, Malaysia, which is a university-based teaching hospital. All hypertensive patients aged 40 or over-registered from January to June 2004, who had been on treatment for at least 3 months, were screened. Previously validated self-administered questionnaires were used to assess the compliance and psychosocial factors. A total of 240 hypertensive patients were recruited in the study. Of these, 55.8% were noncompliant to medication. Logistic regression showed that age (adjusted odds ratio (OR): 0.96; 95% confidence interval (CI): 0.92–0.997; P: 0.035), patient satisfaction (adjusted OR: 0.97; 95% CI: 0.93–0.998; P: 0.036) and medication barrier (adjusted OR: 0.95; 95% CI: 0.91–0.987; P: 0.009) were significant predictors of medication noncompliance. Therefore, younger age, poor patient satisfaction and medication barrier were identified as independent psychosocial predictors of medication noncompliant in hypertensive patients.

Early manifestation of macrovasculopathy in newly diagnosed never treated type II diabetic patients with no traditional CVD risk factors

Type II diabetes patients have increased risk of macrovascular complications compared with the general population. Arterial stiffness is considered as an independent predictor of macrovascular events. This study investigated arterial stiffness in newly diagnosed never treated diabetes and impaired glucose tolerance (IGT) patients without any traditional cardiovascular diseases (CVD) risk factors. After preliminary screening of 1620 individuals, 30 diabetic and 30 IGT patients were recruited and compared with age- and sex-matched 30 normoglycaemic subjects. The subjects were newly diagnosed, never treated, normotensive, non-obese, non-hyperlipidaemic and non-smoker. Haemodynamic variables, pulse wave velocity (PWV) and augmentation index (AI) were measured. The PWV was significantly higher in diabetic patients (10.37+/-2.64m/s vs. 8.70+/-1.29m/s; p=0.035) and was of borderline significant in IGT subjects (9.54+/-1.56m/s vs.8.70+/-1.29m/s, p=0.078) compared to normoglycaemic individuals. Augmentation index was higher of borderline significant in diabetic (134.53+/-17.32% vs. 129.17+/-11.18%, p=0.055) and IGT patients (132.02+/-16.11% vs. 129.17+/-11.18%, p=0.059) compared to normoglycaemic individuals. The study demonstrated that newly diagnosed never treated diabetic patients without any CV complications had early manifestation of macrovascular diseases as evident by increased arterial stiffness. The findings also revealed early manifestations of preclinical vasculopathy and potentially increased risk for development of macrovascular diseases at an early age in diabetic patients.

Blood pressure in acute intracerebral haemorrhage

Stroke is one of the leading causes of death worldwide, and spontaneous bleeding into the brain parenchyma, intracerebral haemorrhage (ICH), is a stroke subtype associated with high morbidity and mortality. Overall, it comprises about 15% of all stroke in Caucasians, this figure being much higher in Asians and black people. Blood pressure (BP) appears to play an important role in this disease. We have reviewed available literature on the relationship of BP to the occurrence of primary and secondary ICH, the association of BP levels measured early after stroke with prognosis and complications, and evidence about the effects of early BP lowering treatments on post-stroke outcomes. BP appears to be an important risk factor for primary and secondary ICH. In addition, high BP early after ICH may be detrimental to outcome, possibly contributing to complications such as rebleeding and haematoma enlargement. Few data are available about the effects of early lowering of BP on outcome after ICH with no reliable trial yet conducted. Proper randomised trials are required to establish the effect of early lowering of BP on outcome after ICH.

The effects of angiotensin II on pulse wave velocity in healthy humans.

OBJECTIVES To examine the dose response relationship between Ang II and pulse wave velocity (an index of arterial stiffness) in healthy human volunteers. DESIGN AND METHODS We studied 9 healthy male volunteers (mean age 24.7 +/- 0.66 years) in a double-blind, randomized, cross-over, placebo-controlled design. We measured carotid-femoral PWV using a novel device complior. Subjects received placebo, 0.5, 1 and 5 ng/kg/min Ang II as infusions over 30 minutes under standardized conditions. Heart rate, blood pressure and PWV were recorded at baseline and then every 10 minutes during the infusion and twice after the end of the infusion. RESULTS Systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) in mmHg increased significantly with the 5 ng/kg/min dose compared to placebo (p = 0.004, p -0.007, p = 0.003, respectively). There was no significant difference in SBP, DBP and MAP between 1 and 0.5 ng/kg/min compared to placebo. There was a significant increase in PWV with 5 ng/kg/min dose only compared to placebo (p = 0.02). However, less than 30% of the total Ang II-induced rise in PWV was explained by the Ang II-induced rise in blood pressure (R2 = 0.257). CONCLUSIONS Ang II increases PWV in healthy human only when given in doses that significantly increase blood pressure. Not all the increase in Ang II-induced rise in PWV can be explained due to Ang II-induced rise in BP.

Effect of rosiglitazone/ramipril on preclinical vasculopathy in newly diagnosed, untreated diabetes and IGT patients: 1-year randomised, double-blind, placebo-controlled study

ObjectiveTo investigate whether pharmacological interventions with rosiglitazone/ramipril can reverse preclinical vasculopathy in newly diagnosed untreated patients with type 2 diabetes (T2DM) and impaired glucose tolerance (IGT).MethodsIn this randomised, double-blind, placebo-controlled study, 33 T2DM and 33 IGT patients were randomised to 4 mg rosiglitazone or 5 mg ramipril or placebo for 1 year. The subjects were newly diagnosed, untreated, normotensive, nonobese, nonsmoker, and nonhyperlipidaemic. Haemodynamic variables were measured at three treatment phases and pulse wave velocity (PWV) and augmentation index (AI) were measured throughout the treatment period.ResultsRosiglitazone showed a significant reduction in PWV (p=0.039) and AI (p=0.031) and ramipril demonstrated a significant reduction of AI (p=0.025) in IGT in comparison to placebo on the 12th month of treatment. No significant difference was observed in PWV and AI in T2DM with rosiglitazone/ramipril in comparison to placebo during overall treatment period.ConclusionsRosiglitazone significantly reversed preclinical vasculopathy in IGT as evident by significant decrease in PWV and AI after 1 year of treatment. Ramipril also reduced large artery stiffness as shown by significant decrease of AI after 1 year of treatment in IGT. Further trials are needed for a longer period of time, maybe with higher doses, to show whether rosiglitazone/ramipril can reverse preclinical vasculopathy in T2DM.

Prediction Models for Early Risk Detection of Cardiovascular Event

Cardiovascular disease (CVD) is the major cause of death globally. More people die of CVDs each year than from any other disease. Over 80% of CVD deaths occur in low and middle income countries and occur almost equally in male and female. In this paper, different computational models based on Bayesian Networks, Multilayer Perceptron, Radial Basis Function and Logistic Regression methods are presented to predict early risk detection of the cardiovascular event. A total of 929 (626 male and 303 female) heart attack data are used to construct the models. The models are tested using combined as well as separate male and female data. Among the models used, it is found that the Multilayer Perceptron model yields the best accuracy result.

Ethnic differences in response to non-selective beta-blockade among racial groups in Malaysia.

OBJECTIVE To determine whether racial differences in response to blockade of beta receptors occur among racial groups in Malaysia that are the Malays, Indians and Chinese. SUBJECTS, MATERIALS AND METHOD: 35 healthy male volunteers representing the 3 main racial groups in Malaysia (12 Malays, 12 Chinese and 11 Indians) were studied in a randomized, placebo-controlled, crossover and single-blind design. Propranolol 80 mg 12-hourly was given orally for 48 hours. Six hours after the last dose subjects attended an exercise session where resting and exercise heart rate, blood pressure, plasma potassium and glucose levels, resting FEV1 and plasma propranolol concentrations were recorded. RESULTS No significant difference in plasma propranolol (mean +/- SEM) levels was seen between races six hours after the last dose (Malays, 59.7 +/- 8.8 ng/ml, Indians, 67.6 +/- 19.3 ng/ml, Chinese, 58.4 +/- 7.9 ng/ml). Chinese were least sensitive to the bradycardic and hypotensive effects of propranolol at rest and exercise. Indians and Malays had significant reduction of supine systolic blood pressure with propranolol but not Chinese. Comparison of percentage reductions of systolic blood pressure at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.022). Similarly, comparison of percentage reductions of heart rate at supine, sitting and exercise by repeated measure analysis showed the Malays to have significantly higher change compared to the Chinese (p = 0.040). Average change in potassium concentrations at peak exercise and recovery showed the Indians to have significantly higher increase in potassium levels with propranolol compared to the Malays (p = 0.038). However, no significant interethnic difference was seen in the reduction of glucose levels at rest, peak exercise or recovery. Also, no significant interethnic difference was seen in reduction of FEV1 values. CONCLUSION We, therefore, conclude that ethnic differences in response to blockade of beta-receptors exist among racial groups in Malaysia. These differences were seen at similar plasma drug levels between races suggesting ethnic differences in drug sensitivity, rather than differences in drug disposition.

The role of β-blockers in the management of hypertension: An Asian perspective

Abstract Following publication of the National Institute of Clinical Excellence (NICE) Guidelines in 2006, the use of β-blockers as first-line therapy in hypertension has been somewhat controversial. However, a recent reappraisal of the European Society of Hypertension guidelines highlights that these agents exhibit similar BP lowering efficacy to other classes of agents, prompting a re-examination of the utility of these agents in various patient populations. The authors felt that it is important to address this controversy and provide an Asian perspective on the place of β-blockers in current clinical practice and the benefits of β-blockade in selected patient populations. In addition to their use as a potential first-line therapy in uncomplicated hypertension, β-blockers have a particular role in patients with hypertension and comorbidities such as heart failure or coronary artery disease, including those who had a myocardial infarction. One advantage which β-blockers offer is the additional protective effects in patients with prior cardiovascular events. Some of the disadvantages attributed to β-blockers appear more related to the older drugs in this class and further appraisal of the efficacy and safety profile of newer β-blockers will lend support to the current guideline recommendations in Asian countries and encourage increased appropriate use of β-blockade in current clinical practice within Asia.