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Biomedical subjects

Sunil Nadar

Publications and source records attributed to Sunil Nadar.

14 recordsLinked to original sources
PubMed2004

Matrix metalloproteinase-9 and tissue inhibitor of metalloproteinase-1 in hypertension and their relationship to cardiovascular risk and treatment: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

BACKGROUND: Hypertension results in structural changes to the cardiac and vascular extracellular matrix (ECM). Matrix metalloproteinases (MMP) and their inhibitors (TIMP) may play a central role in the modulation of this matrix. We hypothesized that both MMP-9 and TIMP-1 would be abnormal in hypertension, reflecting alterations in ECM turnover, and that their circulating levels should be linked to cardiovascular (CHD) and stroke (CVA) risk scores using the Framingham equation. Second, we hypothesized that treatment would result in changes in ECM indices. METHODS: Plasma MMP-9 and TIMP-1 were measured before and after treatment (median 3 years) from 96 patients with uncontrolled hypertension participating in the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Pretreatment values were compared to circulating MMP-9 and TIMP-1 levels in 45 age- and sex-matched healthy controls. RESULTS: Circulating pretreatment MMP-9 and TIMP-1 levels were significantly higher in patients with hypertension than in the normotensive controls (P =.0041 and P =.0166, respectively). Plasma MMP-9 levels decreased, and TIMP-1 levels increased after treatment (P =.035 and P =.005, respectively). Levels of MMP-9 correlated with CHD risk (r = 0.317, P =.007) and HDL cholesterol (r = -0.237, P =.022), but not CVA risk. There were no significant correlations between TIMP-1 and CVA or CHD scores. CONCLUSIONS: Increased circulating MMP-9 and TIMP-1 at baseline in patients with hypertension could reflect an increased deposition and retention of type I collagen at the expense of other components of ECM within the cardiac and vascular ECM. After cardiovascular risk management, MMP-9 levels decreased and TIMP-1 levels increased. Elevated levels of MMP-9 also appeared to be associated with higher Framingham cardiovascular risk scores. Our observations suggest a possible role for these surrogate markers of tissue ECM composition and the prognosis of cardiovascular events in hypertension.

Aged↗
PubMed2004

Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipine-based antihypertensive therapy.

BACKGROUND AND AIM: Platelet abnormalities have been described in hypertension, especially in the presence of target organ damage. Our aim was to study the differences in morphology and indices of platelet activation in treatment-naive patients with essential hypertension as compared to normotensive controls and secondly, to study the effects of amlodipine-based antihypertensive therapy on these indices. METHODS: We recruited 42 previously untreated, newly diagnosed hypertensive patients (25 men; mean age 53 years) for the cross-sectional study, where data were compared with those from 30 normotensive controls (20 men; mean age 57 years). Of the 42 untreated hypertensive patients who were recruited, 27 patients successfully completed, the six-month treatment phase with amlodipine-based antihypertensive therapy. Platelet morphology (volume and mass) was quantified, and plasma markers of platelet activation (betaTG and sPsel) measured in citrated plasma. The mass of P-selectin in each platelet (pPsel) was determined by lysing a fixed number of platelets and then determining the levels of P-selectin in the lysate. RESULTS: Hypertensive patients had significantly higher platelet volume (P = 0.01) and mass (P = 0.003), plasma betaTG and sPsel, and pPsel levels (all P < 0.001) compared to the controls. After a mean treatment time of 6 months, there was a decrease in platelet volume (P < 0.001) and mass (P = 0.02), with lower pPsel, sPsel and BTG levels (all P < 0.001) compared to the untreated state. CONCLUSION: Treatment of uncomplicated essential hypertension using amlodipine-based anti-hypertensive therapy results in a reversal of the platelet morphology abnormalities and indices of platelet activation. This may contribute to a reduction in thrombosis-related complications seen in those whose blood pressure lowering is effective.

Amlodipine↗
PubMed2004

Platelet activation in the hypertensive disorders of pregnancy.

The hypertensive disorders of pregnancy, including gestational hypertension, pre-eclampsia and eclampsia, continue to be an important cause of maternal morbidity and mortality. Abnormal placentation is considered to be the main instigating factor, which then leads to widespread maternal endothelial activation and dysfunction. This endothelial perturbation leads to the release of many substances into the circulation, many of which result in platelet activation. For example, there is an imbalance between the levels of prostacyclin (a vasodilator and platelet inhibitor) and thromboxane (a platelet activator and vasoconstrictor), which then results in the maintenance of high blood pressure and complications. It is also likely that platelets play an important part in the pathogenesis of hypertension in pregnancy. The use of antiplatelet drugs has been shown to be effective in reducing the incidence of gestational hypertension in women at high risk and in preventing the complications associated with it. In addition, some antihypertensive agents are effective in reversing platelet activation in essential hypertension and, therefore, their use in pregnancy-induced hypertension may be beneficial in more ways than simply blood pressure reduction.

Female↗
PubMed2003

Pharmacological modulation of platelet function in hypertension.

Platelets exert a considerable influence on human morbidity and mortality. The rationale for their study in hypertension follows the observation that the major consequences of hypertension are stroke and myocardial infarction. However, the etiology of these consequences in hypertension is, paradoxically, not hemorrhagic (as might be expected from the effects of high blood pressure), but occlusive, with thrombus being the culprit lesion. Mechanisms of platelet activation include high shear force, activation of the renin-angiotensin system, endothelial changes, and the presence of comorbidity, such as atrial fibrillation. The treatment of high blood pressure brings about a reversal of the changes seen in the cell. This could be in part due to the direct effect of the drug on the megakaryocyte and/or the platelets themselves, or it might simply be due to the reduction in blood pressure. Some drugs, such as calcium channel antagonists and angiotensin II receptor blockers, however, might have direct effects on platelet biochemistry other than reducing blood pressure. Finally, antiplatelet drugs are becoming an important part of the management of high-risk hypertensives, which aim to minimize vascular complications.

Antihypertensive Agents↗
PubMed2003

Patients' understanding of anticoagulant therapy in a multiethnic population.

To investigate whether knowledge and perceptions of antithrombotic therapy differ between ethnic groups in the UK, we conducted a cross-sectional questionnaire survey of patients attending anticoagulation clinics in three Birmingham teaching hospitals. 180 consecutive patients were recruited-135 white European, 29 Indo-Asian, 16 Afro-Caribbean. The average knowledge score was 5.5 out of 9, with no significant differences between the groups. Indo-Asians were significantly less likely than the other groups to know the name of the anticoagulant they were taking (warfarin) and Afro-Caribbeans to know the condition for which they were being anticoagulated. Few patients of any group were able to specify more than one side-effect of warfarin or the dose they were on. In logistic regression analysis the factors associated with a low score were age >61 years, having been born outside the UK, and the perception of difficulty in comprehension. Nearly half the Indo-Asians felt unable to understand what was said to them in the clinic, and 62% expressed a preference for a doctor of the same ethnic group. Although there were no significant between-group differences, this study points to gaps in the knowledge of patients from ethnic minorities and to deficiencies in the provision of information. In patient education, these groups should receive special attention.

Adult↗
PubMed2003

Primary hyperaldosteronism.

Primary hyperaldosteronism is an important cause of hypertension. Its true prevalence is still a matter of debate, since about 10% of hypertensives may have underlying hyperaldosteronism. Primary hyperaldosteronism is due to aldosterone-secreting tumours, bilateral adrenal hyperplasia or, rarely, adrenal carcinoma or genetic causes. There is considerable debate over the optimal screening methods for detecting hyperaldosteronism. The patients who benefit the most from screening are young hypertensives, those with resistant hypertension and patients with serum potassium of less than 3.5 mmol/L, especially in the presence of a high sodium. Various tests are available for screening patients with hypertension for hyperaldosteronism. Serum potassium is an unreliable marker for hyperaldosteronism, although a low value in a patient not taking diuretics should make one suspect the diagnosis. The use of serum potassium as a screening test would miss about a third of cases. Determination of the ratio of plasma aldosterone concentration to plasma renin activity is widely accepted as the test of choice for screening. Tests such as diurnal variations in aldosterone concentration and response to angiotensin II help to demonstrate the autonomy of the aldosterone secretion. Once the diagnosis of hyperaldosteronism is made, further tests such as magnetic resonance imaging or computed tomographic scanning and adrenal vein sampling should be undertaken to determine the aetiology of the hyperaldosteronism. Depending on the findings and the lateralization of the lesion, either surgery or medical therapy may be advised for the patient. Spironolactone would be the drug of choice for medical treatment. Laparoscopic adrenalectomy has become a widely employed method of surgically removing adrenal tumours. Hyperaldosteronism represents one of the few treatable causes of hypertension and a systematic approach is therefore needed to ensure that the few patients with an aldosterone-secreting adrenal adenoma are identified. It is important to identify these patients so that only those patients with proven adenomas are referred for adrenalectomy.

Humans↗
PubMed2003

Implications of the LIFE trial.

The recent Losartan Intervention For Endpoint Reduction in Hypertension (LIFE) study was conducted in patients with essential hypertension with electrocardiogram evidence of left ventricular hypertrophy. This showed that losartan compared to atenolol resulted in a significant reduction in the primary endpoint of cardiovascular morbidity and mortality, as well as a greater reduction in electrocardiographically-defined left ventricular hypertrophy. Importantly, this was despite a mean blood pressure reduction which was similar in both groups. Furthermore, the atenolol arm was associated with higher incidence of newly diagnosed diabetics. The LIFE study has firmly confirmed a place for losartan (and other angiotensin receptor blockers) in the management of hypertension. Losartan has also been shown to be effective in diabetics and in patients with atrial fibrillation, as well as in left ventricular hypertrophy regression. This trial also raises the possibility that beta-blockers should perhaps not be used as first-line monotherapy.

Adrenergic beta-Antagonists↗
PubMed2003

The prothrombotic state in hypertension and the effects of antihypertensive treatment.

Hypertension is associated with the flow of blood under high pressures, yet the complications of hypertension, such as myocardial infarction or stroke are paradoxically thrombotic rather than haemorrhagic. This could be explained by increasing evidence which suggests that hypertension fulfils the pre-requisites of the Virchow's triad for thrombogenesis, leading to a prothrombotic or hypercoagulable state. Hypertension leads to changes in the platelets, endothelium and the coagulation and fibrinolytic pathways which help to promote the induction and the maintenance of this prothrombotic state. These changes can to a certain extent be reversed by the treatment of hypertension, although different antihypertensive agents may have variable effects in reversing these changes. Some of the effects may be simply related to normalisation of blood pressure, but certain groups of drugs such as those acting on the renin-angiotensin-aldosterone system appear to have an effect over and above this. Anti-platelet agents have also been shown to confer a degree of benefit to lsqou;high risk' hypertensive patients. The study of the prothrombotic state in hypertension is therefore of paramount importance, as understanding the pathogenic processes underlying it can help prevent many of the complications associated with this condition.

Antihypertensive Agents↗
PubMed2002

Ongoing trials involving angiotensin-converting enzyme inhibitors.

Angiotensin-converting enzyme inhibitors (ACEIs) are an important class of drugs in cardiovascular disease. As their name suggests, they act by blocking angiotensin converting enzyme, thereby limiting the production of angiotensin II, the most active component of the renin-angiotensin- aldosterone system. This system plays an important role in maintenance of blood pressure and electrolyte and fluid balance. Therefore, by blocking this system, the ACEIs have wide ranging effects. Recent trials have reaffirmed their place in the management of hypertension, congestive cardiac failure, in the prevention of renal complications in diabetes and the prevention of strokes in 'at risk' patients. There are still many ongoing trials using the ACEIs. These trials are mainly aimed at comparing their efficacy with 'older' drugs (such as betablockers) and 'newer' drugs such as the angiotensin receptor blockers and calcium antagonists in different indications, such as heart failure and diabetic nephropathy. The impact of these drugs on the prevention of macro- and micro vascular complications in diabetes is also being investigated. The results of all these trials, when available, are expected to reaffirm the important role of this class of drugs in our modern day medical armamentarium. In this review, the ongoing clinical trials involving ACEIs, the rationale behind these trials and what impact they hope to have on our current understanding of the role of this important class of drug in medical practice, will be discussed.

Angiotensin-Converting Enzyme Inhibitors↗