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Biomedical subjects

D Gareth Beevers

Publications and source records attributed to D Gareth Beevers.

16 recordsLinked to original sources
PubMed2004

Platelet indexes in relation to target organ damage in high-risk hypertensive patients: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

OBJECTIVES: We sought to investigate the relationship between target organ damage (TOD) in hypertension and a prothrombotic/hypercoagulable state, using a new technique of "platelet lysis" to quantify the amount of P-selectin per platelet (pP-sel), and to correlate it with other platelet markers (e.g., mass, volume and granularity, soluble P-selectin [sP-sel], and beta-thromboglobulin [beta-TG]). BACKGROUND: The increased risk of TOD in hypertension may be related to a prothrombotic/hypercoagulable state, with abnormalities in platelets, such as increased expression of P-selectin. METHODS: We studied 199 patients (mean age 68 years, 75% men) with hypertension. Of these, 125 had TOD (e.g., stroke, previous myocardial infarction, angina, left ventricular hypertrophy). Values obtained were compared with those from 59 healthy normotensive control subjects (mean age 68 years, 58% men). RESULTS: Hypertensive patients had a higher mean platelet volume, mass, pP-sel, sP-sel, and beta-TG and lower platelet granularity (all p < 0.01), but a similar platelet count, as compared with controls. Within the hypertensive group, those with evidence of TOD had significantly larger platelets with greater mass but had lower granularity, sP-sel, and pP-sel levels than those without TOD, possibly reflecting increased aspirin use. On multivariate analysis, aspirin use was a determinant of pP-sel (p = 0.03) and sP-sel (p = 0.01), but the use of other drugs or other co-morbidity (e.g., diabetes, smoking) did not influence either P-selectin value. CONCLUSIONS: Patients with hypertension have evidence of changes in platelet physiology, as reflected by a higher level of pP-sel. Patients with TOD also had larger platelets, with greater mass, and the use of aspirin lowered pP-sel and sP-sel levels. These changes may have implications for the pathophysiology of cardiovascular and cerebrovascular disease in hypertension.

Aged↗
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

Effects of losartan versus hydrochlorothiazide on indices of endothelial damage/dysfunction, angiogenesis and tissue factor in essential hypertension.

BACKGROUND: Abnormalities in endothelial function, angiogenesis and thrombogenesis are found in essential hypertension. Angiotensin II has been postulated as an agent involved in these processes. We hypothesized that the treatment of essential hypertension with the angiotensin II receptor antagonist, losartan, would affect endothelial damage/dysfunction, angiogenesis and coagulation, when compared to treatment with a diuretic. METHODS: Forty hypertensive patients (28 male, mean age 56 +/- 11.8 years) were randomized to treatment with losartan 50-100 mg o.d. or hydrochlorothiazide 12.5-25 mg o.d. over a 12-week period. Patients were assessed at week 0, 4 and 12. Endothelial damage/dysfunction was assessed using plasma levels of von Willebrand factor (vWf) and changes in flow-mediated dilation of the brachial artery (FMD). Vascular endothelial growth factor (VEGF) and its soluble receptor Flt-1 (sFlt-1) were measured as indices of angiogenesis, and plasma tissue factor (TF) as an index of coagulation. Baseline results in hypertensives were compared to 20 healthy controls (13 male, mean age 61.1 +/- 10.1 years). RESULTS: Mean patient BP was 161/95 +/- 21/18 mmHg compared to 134/81 +/- 11/7 mmHg in controls (p<0.002). Plasma levels of TF (p=0.023) were significantly higher in patients compared to controls, and FMD was significantly lower (p<0.001). There were no significant differences in baseline blood pressures, plasma indices or FMD between patients randomized to losartan and hydrochlorothiazide. There were no significant changes in levels of plasma indices or FMD over 12 weeks of treatment in either patient group. Significant correlations between levels of VEGF with sFlt-1 (Spearman p<0.001) and TF (p=0.009) and sFlt-1 and TF (p=0.035) were seen in the untreated state, amongst the patient group only. CONCLUSION: We have confirmed previous observations of increased levels of TF and decreased FMD in hypertensive patients compared to healthy controls. Contrary to previous observations in higher-risk hypertensive patient groups, the treatment of essential hypertension with either losartan or hydrochlorothiazide did not affect indices of endothelial damage/dysfunction, angiogenesis or coagulation.

Adult↗
PubMed2004

Salt intake and Helicobacter pylori infection.

BACKGROUND: The chance finding of an association between Helicobacter pylori infection and hypertension and the known relationship between salt intake and blood pressure led us to speculate whether these two environmental factors might be related. A positive relationship between them might suggest that a high-salt diet could in some way facilitate gastric H. pylori infection. METHODS: We have therefore conducted an ecological study of the national H. pylori infection rates in the EUROGAST study and national salt excretion levels with the INTERSALT project. Ten nations were included in both projects. RESULTS: Statistically significant correlation between H. pylori infection rates and salt excretion were found in older men and women (r = 0.728 and r = 0.827, respectively) and in younger men (r = 0.728), but not younger women (r = 0.519). CONCLUSIONS: Our findings raise the possibility that salt intake may in some way facilitate H. pylori infection. A dedicated population survey is now justifiable to investigate the role of salt intake in H. pylori infection with the measurement of all possible confounding variables including particularly socio-economic status

Helicobacter Infections↗
PubMed2003

Relation of thrombogenesis in systemic hypertension to angiogenesis and endothelial damage/dysfunction (a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial [ASCOT]).

Increasing evidence points toward a prothrombotic state in hypertension and atherosclerosis, conditions associated with thrombosis-related complications, such as myocardial infarction and stroke. We hypothesized that this increased risk of thrombogenesis may be related to endothelial damage/dysfunction and abnormal angiogenesis, and thus, an increased risk of future cardiovascular disease. Thrombogenesis, endothelial damage/dysfunction, and angiogenesis can be assessed by measurement of tissue factor (TF), von Willebrand Factor (vWF), flow-mediated dilatation (FMD), and vascular endothelial growth factor (VEGF), respectively. To test this hypothesis, we measured TF, vWF, FMD, and VEGF in 76 patients with systemic hypertension (71 men; mean age 64; mean blood pressure 167/72 mm Hg), considered additional risk factors such as diabetes, and related them to the patient's 10-year cardiovascular and cerebrovascular risk score using the Framingham equation. Patients were compared with 48 healthy normotensive controls. In these patients, the effects of 6 months of intensified blood pressure and (where appropriate) lipid-lowering treatment were investigated. In our patients, TF, VEGF, and vWF levels were higher, but FMD was lower (all p <0.001) compared with the controls. All markers correlated with each other and with both cardiovascular and cerebrovascular risk scores (all p <0.001). After intensified blood pressure and hypercholesterolemia treatment, total cholesterol, blood pressure, TF, VEGF, and vWF levels all decreased, whereas FMD increased (all p <0.001). Thus, in subjects with hypertension and other risk factors, endothelial damage/dysfunction (and thus, atherogenesis), thrombogenesis, and angiogenesis are abnormal, correlate with overall cardiovascular risk, and importantly, can be related to each other in a "Birmingham Vascular Triangle." Furthermore, these processes are beneficially affected by intensive blood pressure and lipid treatment.

Arteriosclerosis↗
PubMed2003

Low-density lipoprotein subfractions and cardiovascular risk in hypertension: relationship to endothelial dysfunction and effects of treatment.

Although hypertensive patients are at particular risk of vascular complications, the possible contribution of an atherogenic lipoprotein profile and endothelial dysfunction to this risk is unclear. We investigated this by measuring LDL subfractions and flow-mediated dilation (FMD) (reflecting endothelial dysfunction) in a cohort of high-risk hypertensive patients. We studied 84 hypertensive patients (74 men; mean age, 64 years; SD 8). Chylomicron-free LDL subfractions were analyzed by disc polyacrylamide gel electrophoresis, producing an LDL score, with higher scores being equivalent to a greater proportion of the more atherogenic LDL subfractions. High-resolution ultrasound was used to assess endothelium-dependent brachial artery FMD after reactive hyperemia after vessel occlusion. Baseline levels were compared with 61 age- and gender-matched healthy normotensive control subjects. Mean LDL score was higher and FMD impaired in hypertensive subjects compared with control subjects. These indexes were significantly improved after 6 months of cardiovascular risk factor management. LDL score correlated significantly with the 10-year Framingham coronary heart disease risk score, with a negative correlation with FMD (both P<0.001). Abnormal atherogenesis and endothelial dysfunction are both present in hypertension and appear to be related to each other, potentially leading to vascular complications. The abnormal LDL scores also correlate with the 10-year cardiovascular risk and can be positively influenced by cardiovascular risk management.

Cardiovascular Diseases↗
PubMed2003

Endothelial damage and angiogenesis in hypertensive patients: relationship to cardiovascular risk factors and risk factor management.

BACKGROUND: Hypertensive patients are at particular risk of cardiovascular complications, possibly related to endothelial damage or dysfunction, or to abnormal angiogenesis. These pathophysiologic processes are assessable by measurement of plasma levels of von Willebrand factor (vWf), and by vascular endothelial growth factor (VEGF) and its soluble receptor (sFlt-1). We hypothesized that these markers would correlate with the Framingham cardiovascular risk score and would be responsive to treatment. METHODS: We measured these markers by enzyme-linked immunosorbent assay in 286 patients with hypertension (239 men; mean age 63 years; mean systolic blood pressure [BP]/diastolic BP 162/89 mm Hg) and additional risk factors, and related them to the patient's cardiovascular disease (CVD) and cerebrovascular accident (CVA) risk, using the Framingham equation. Patients were compared with 60 healthy normotensive controls. In 248 patients, the effects of 6 months of intensified cardiovascular risk factor management, including BP and (where appropriate) lipid-lowering treatment, were investigated. RESULTS: Plasma VEGF and vWf levels were higher, but sFlt-1 levels lower (all P <.001), in the hypertensive patients compared with the controls. The VEGF and vWf levels correlated significantly with age, systolic and diastolic BP, 10-year CVD risk, and CVA risk scores (all P <.01), whereas sFlt-1 was negatively correlated with these risk scores (P <.01). After intensified cardiovascular risk factor management, total cholesterol, BP, VEGF, and vWf levels were all reduced, yet sFlt-1 levels increased (all P <.05). CONCLUSIONS: In hypertension, the processes of endothelial damage and angiogenesis are abnormal, and correlate with overall cardiovascular risk. Indices of endothelial damage and angiogenesis are beneficially changed by intensive cardiovascular risk factor management.

Adult↗
PubMed2003

beta-Blockers in hypertension-the emperor has no clothes: an open letter to present and prospective drafters of new guidelines for the treatment of hypertension.

Over the past decade, national and international guidelines have proposed beta-blockers to be used on an equal footing with diuretics for initial therapy of hypertension. This preferred status was supposedly based on evidence documenting a reduction in morbidity and mortality with beta-blocker therapy in hypertension. We systematically analyzed all available outcome studies and found no evidence that beta-blocker based therapy, despite lowering blood pressure, reduced the risk of heart attacks or strokes. Despite the inefficacy of beta-blockers, the incidence of adverse effects is substantial. In the MRC study, for every heart attack or stroke prevented, three patients withdrew from atenolol because of impotence, and another seven withdrew because of fatigue. Thus the risk/benefit ratio of beta-blockers is characterized by lack of efficacy and multiple adverse effects. Given that many thorough, prospective, randomized trials attest to efficacy and safety of diuretics, calcium antagonists, ACE inhibitors, and angiotensin receptor inhibitors, the time has come to admit that beta-blockers should no longer be considered appropriate for first-line therapy in uncomplicated hypertension.

Adrenergic beta-Antagonists↗
PubMed2003

Alcohol and cardiovascular disease--more than one paradox to consider. Alcohol and hypertension--does it matter? (no!).

Good evidence suggests that alcohol probably has a causal relationship to hypertension, although many possible confounding factors that may exaggerate or attenuate the relationship, if true. Alcohol can also adversely affect other systems, including the heart (arrhythmias, alcoholic cardiomyopathy, etc.), the liver (alcoholic hepatitis, cirrhosis, etc.) and the nervous system (peripheral neuropathy, etc.). Hypertension is very common and it is unlikely that all (or most) of hypertensives can identify alcohol as causative. Indeed, hypertension is likely to be multifactorial and many factors would confound the relationship, if any, between alcohol and hypertension.

Age Factors↗
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↗
PubMed2002

Hypertension, left ventricular hypertrophy, and sudden death.

Left ventricular hypertrophy (LVH), a form of end-organ damage in hypertension, is associated with increased incidence of sudden cardiac death (SCD). This review explores the possible mechanisms behind this phenomenon. SCD in LVH could be thrombotic/ischemic or arrhythmic (eg, myocardial ischemia, even in the absence of significant coronary artery disease, may be one important factor). Abnormalities of flow-mediated dilatation, endothelial function, and a hypercoagulable state are well-observed abnormalities in association with hypertension and LVH, although their precise contributory role is as yet undefined in the pathogenesis of sudden death. Electrophysiologic abnormalities are also well documented in LVH, and such patients are more predisposed to arrhythmias. In the past decade, many studies have investigated the regression of LVH, and recent studies are addressing whether the latter translates into a prognostic benefit.

Arrhythmias, Cardiac↗
PubMed2002

In-hospital symptoms of depression do not predict mortality 3 years after myocardial infarction.

BACKGROUND: The main aim of this study was to examine the relationship between symptoms of depression following myocardial infarction (MI) and 3-year survival status. METHODS: The Beck Depression Inventory was completed by 288 patients hospitalized for MI. Patients' cardiological status, including indices of disease severity, were recorded or derived from hospital notes. Three-year survival status was determined using patient information systems and cause of death ascertained from death certificates. RESULTS: During the 3 years of follow-up, 38 patients (13%) died, 33 (11%) from cardiac causes. Symptoms of depression did not predict either cardiac-specific or all-cause mortality. Similarly, in-hospital levels of anxiety were not associated with prognosis. In contrast, measures of disease severity and discharge medication status were strong prognostic indicators. Depression was not related to measures of disease severity at entry to the study. CONCLUSIONS: Symptoms of depression following MI do not predict longer-term survival, although measures of disease severity and discharge medication status do. Previous positive results for depression and cardiac mortality in MI patients could reflect the occasional confounding of depression with disease severity.

Aged↗
PubMed2002

Inter-arm differences in blood pressure: when are they clinically significant?

OBJECTIVE: To determine whether there is significant disparity in blood pressure between the two arms. DESIGN: Prospective, observational study. SETTING: One general hospital in Birmingham, England. PARTICIPANTS: Four hundred participants [age 56.3 +/- 19.7 years (mean +/- SD), 50% male] were recruited from staff and patients. Simultaneous bilateral blood pressure measurements were obtained using Omron HEM-705CP automated oscillatory devices; with two measurements taken in each arm. MAIN OUTCOME MEASURES: Mean inter-arm blood pressure differences and frequency of clinically important disparities. RESULTS: Mean +/- SD inter-arm differences in systolic and diastolic blood pressure were 1.81 +/- 8.6 mmHg and -0.23 +/- 8.3 mmHg, respectively. The analogous figures for mean +/- SD absolute differences were 6.32 +/- 6.12 mmHg and 5.06 +/- 6.57 mmHg, respectively. Significant differences were present between the mean right and left arm systolic blood pressure [t(399) = 4.20, P < 0.0001], and the mean absolute difference for both systolic [t(399) = 20.65; P < 0.0001] and diastolic [t(399) = 15.39; P < 0.0001] blood pressure. The variation in mean inter-arm blood pressure was unrelated to age, sex, ethnicity, arm circumference, handedness, being hypertensive, diabetic, or previous history of cardiovascular disease. Clinically significant inter-arm differences in systolic blood pressure of > 10 and > 20 mmHg were found in 20 and 3.5%, respectively; diastolic differences of > 10 and > 20 mmHg were present in 11 and 3.5%, respectively. Age was the only significant predictor of clinically significant variations in inter-arm blood pressures and mean absolute blood pressure differences. CONCLUSIONS: Significant differences in mean inter-arm systolic blood pressure, and mean absolute inter-arm systolic and diastolic blood pressure are present. This emphasizes the importance of measuring blood pressure in both arms initially to prevent this misdiagnosis of hypertension, due to normal differences in blood pressure between the arms.

Adult↗
PubMed2002

Von Willebrand factor, soluble P-selectin, and target organ damage in hypertension: a substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT).

To investigate the relationship between soluble markers of platelet, endothelial and rheological function, and target organ damage and their response to intensified management in a population of middle-age hypertensive patients at high risk of cardiovascular complications, we studied 382 consecutive patients (308 men; mean age, 63 years, SD 8) along with 60 normotensive controls free of cardiovascular disease. Patients were divided into those with target organ damage (TOD; n=107) and those free of end-organ damage. Plasma levels of soluble P-selectin (sP-sel), a marker of platelet activation, and von Willebrand factor (vWF), an index of endothelial damage/dysfunction (both enzyme-linked immunosorbent assay), and the rheological indices fibrinogen, plasma viscosity, hematocrit, platelet, and white cell count were measured. In 53 patients, variables were further measured after 6 months of intensified cardiovascular risk management. Patients with TOD had significantly higher vWF, 137 (SD 33) versus 125 (SD 33) IU/dL (P=0.002,) and a greater proportion of smokers, 31% versus 16% (P=0.002). There were no statistically significant differences in plasma viscosity, fibrinogen, hematocrit, white blood cell count, platelet count, or sP-sel between the 2 subgroups. In multivariate analysis, vWF was a significant independent predictor for TOD. After 6 months of intensified management in 53 patients who entered the trial, there were significant reductions in systolic blood pressure, total cholesterol, hematocrit, plasma viscosity, sP-sel, and vWF (all P<0.01) but no significant change in fibrinogen. In conclusion, there is a relationship between TOD and endothelial damage/dysfunction in hypertension. Intensified management results in improvements in hemorheology, endothelial and platelet function.

Adult↗
PubMed2002

The prevalence and persistence of depression and anxiety following myocardial infarction.

OBJECTIVES: This study was designed to assess the prevalence and persistence of symptoms of depression and anxiety during the first 12 months following acute myocardial infarction (MI). DESIGN AND METHODS: In a prospective study, 288 MI patients were assessed for symptoms of depression and anxiety using the Beck Depression Inventory (BDI) and the State-Trait Anxiety Inventory (STAI) in hospital, 2-15 days following MI, and 4 and 12 months subsequently. RESULTS: During hospitalization, 89 (30.9%) and 75 (26.1%) patients registered elevated BDI scores (>/=10) and state anxiety scores (>/=40), respectively. The 4 and 12 month prevalence rates were 37.7% and 37.2% for depressive symptoms, and 41.8% and 40.0% for anxious symptoms, respectively. Depression and anxiety were highly co-morbid, with 51% of patients experiencing significant levels of depressive and anxious symptoms at baseline. More than half the patients with complete BDI and state anxiety data experienced either elevated symptoms of anxiety or depression throughout the first year following MI. CONCLUSIONS: Symptoms of depression and anxiety are prevalent, persistent problems during the first year following MI. This study highlights the importance of routine psychological assessment for MI patients both in hospital and after discharge.

Journal Article↗