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"Beevers, D Gareth"
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تمثل سلسلة \"كتب طبيب العائلة\" مصدر معلومات مثالي للمرضى. فهي تتضمن معلومات واضحة وموجزة وحديثة ومنصوصة من قبل الخبراء الرائدين، إنها المعيار الذهبي الحالي في مجال توفير المعلومات للمرضى. وأما الخصائص التي تتميز بها كتب طبيب العائلة فهي : 1- مكتوبة من قبل استشاريين رائدين في مجالات الاختصاص 2- منشورة بالتعاون مع الرابطة الطبية البريطانية 3- خاضعة للتحديث والمراجعة من قبل الأطباء بشكل منتظم.
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Role of blood pressure and other variables in the differential cardiovascular event rates noted in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA)
Results of the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) show significantly lower rates of coronary and stroke events in individuals allocated an amlodipine-based combination drug regimen than in those allocated an atenolol-based combination drug regimen (HR 0·86 and 0·77, respectively). Our aim was to assess to what extent these differences were due to significant differences in blood pressures and in other variables noted after randomisation.
We used data from ASCOT-BPLA (n=19 257) and compared differences in accumulated mean blood pressure levels at sequential times in the trial with sequential differences in coronary and stroke events. Serial mean matching for differences in systolic blood pressure was used to adjust HRs for differences in these events. We used an updated Cox-regression model to assess the effects of differences in accumulated mean levels of various measures of blood pressure, serum HDL-cholesterol, triglycerides and potassium, fasting blood glucose, heart rate, and bodyweight on differences in event rates.
We noted no temporal link between size of differences in blood pressure and different event rates. Serial mean matching for differences in systolic blood-pressure attenuated HRs for coronary and stroke events to a similar extent as did adjustments for systolic blood-pressure differences in Cox-regression analyses. HRs for coronary events and stroke adjusted for blood pressure rose from 0·86 (0·77–0·96) to 0·88 (0·79–0·98) and from 0·77 (0·66–0·89) to 0·83 (0·72–0·96), respectively. Multivariate adjustment gave HRs of 0·94 (0·81–1·08) for coronary events (HDL cholesterol being the largest contributor) and 0·87 (0·73–1·05) for stroke events.
Multivariate adjustment accounted for about half of the differences in coronary events and for about 40% of the differences in stroke events between the treatment regimens tested in ASCOT-BPLA, but residual differences were no longer significant. These residual differences could indicate inadequate statistical adjustment, but it remains possible that differential effects of the two treatment regimens on other variables also contributed to the different rates noted, particularly for stroke.
Journal Article
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)
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.
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.
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.
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.
Journal Article
Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial
The apparent shortfall in prevention of coronary heart disease (CHD) noted in early hypertension trials has been attributed to disadvantages of the diuretics and β blockers used. For a given reduction in blood pressure, some suggested that newer agents would confer advantages over diuretics and β blockers. Our aim, therefore, was to compare the effect on non-fatal myocardial infarction and fatal CHD of combinations of atenolol with a thiazide versus amlodipine with perindopril.
We did a multicentre, prospective, randomised controlled trial in 19 257 patients with hypertension who were aged 40–79 years and had at least three other cardiovascular risk factors. Patients were assigned either amlodipine 5–10 mg adding perindopril 4–8 mg as required (amlodipine-based regimen; n=9639) or atenolol 50–100 mg adding bendroflumethiazide 1·25–2·5 mg and potassium as required (atenolol-based regimen; n=9618). Our primary endpoint was non-fatal myocardial infarction (including silent myocardial infaction) and fatal CHD. Analysis was by intention to treat.
The study was stopped prematurely after 5·5 years' median follow-up and accumulated in total 106 153 patient-years of observation. Though not significant, compared with the atenolol-based regimen, fewer individuals on the amlodipine-based regimen had a primary endpoint (429 vs 474; unadjusted HR 0·90, 95% CI 0·79–1·02, p=0·1052), fatal and non-fatal stroke (327 vs 422; 0·77, 0·66–0·89, p=0·0003), total cardiovascular events and procedures (1362 vs 1602; 0·84, 0·78–0·90, p<0·0001), and all-cause mortality (738 vs 820; 0·89, 0·81–0·99, p=0·025). The incidence of developing diabetes was less on the amlodipine-based regimen (567 vs 799; 0·70, 0·63–0·78, p<0·0001).
The amlodipine-based regimen prevented more major cardiovascular events and induced less diabetes than the atenolol-based regimen. On the basis of previous trial evidence, these effects might not be entirely explained by better control of blood pressure, and this issue is addressed in the accompanying article. Nevertheless, the results have implications with respect to optimum combinations of antihypertensive agents.
Journal Article
Endothelial dysfunction in hypertension in pregnancy: associations between circulating endothelial cells, circulating progenitor cells and plasma von Willebrand factor
Background
Endothelial damage/dysfunction has been related to hypertension in pregnancy, with implications in pregnancy outcomes. We hypothesised abnormal levels of circulating endothelial cells (CECs), circulating progenitor cells (CPCs) and plasma von Willebrand factor (vWf, a marker of endothelial damage/dysfunction) in pregnant women with hypertension, when compared to pregnant normotensives and non pregnant healthy controls.
Methods
Our study groups were 3rd trimester hypertensive pregnant women, 40 age matched normotensive pregnant women and 50 non pregnant healthy controls. CECs were measured by immunomagnetic separation using anti-CD146 monoclonal antibody coated beads. CPCs were defined using flow cytometry as CD133+/CD34+/CD45−. vWf was measured by ELISA.
Results
Hypertensive pregnant women had significantly higher CECs compared to normotensive pregnant women and non pregnant healthy controls (
p
< 0.001). CPCs were raised in the normotensive pregnant group compared with hypertensive pregnant and non pregnant healthy controls (
p
< 0.05). Both pregnant women groups had significantly higher vWF than the non pregnant controls. CEC levels correlated with both systolic and diastolic BP (
r
= 0.28,
p
< 0.005 and
r
= 0.31,
p
< 0.001, respectively). vWf correlated with CECs (
r
= 0.39,
p
< 0.0001). Multiple linear regression analysis revealed hypertension in pregnancy as an independent predictor of CEC levels (
p
< 0.0001).
Conclusions
Hypertension in pregnancy is characterised by abnormalities in the vascular endothelium, with abnormal CECs and vWf that correlate with BPs. This may reflect dysfunctional processes that are counteracted with reparative attempts at restoring endothelial integrity.
Journal Article
Endothelial damage and angiogenesis in hypertensive patients: relationship to cardiovascular risk factors and risk factor management
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.
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.
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).
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.
Journal Article
Improving Survival of Malignant Hypertension Patients Over 40 Years
Background To examine changing demography and survival of patients with malignant phase hypertension (MHT) over 40 years. Methods Patients from our MHT registry whose survival status on 31 December 2006 was known were included, with analyses conducted based on decade of MHT diagnosis. Results Four-hundred and forty-six patients with MHT (overall mean (s.d.) age 48.2 (12.9), years; 65.5% male; 64.7% white-European; 20.4% African Caribbean, and 14.8% South-Asian) were included. No significant demographic differences at diagnosis were evident over the 40 years, with the exception of a significant increase (P = 0.001) in the proportion of MHT among ethnic minorities (South-Asian and Afro-Caribbeans). There were no significant differences in mean systolic blood pressure (SBP) at presentation but baseline diastolic BP (DBP) was significantly lower after 1976 (P < 0.0001). The total number of person-years of observation was 5,725.5 years, with a median (interquartile range (IQR)) length of follow-up of 103.8 (31.3–251.2) months. Overall 203 patients (55.6%) died, 125 (32.0%) within 5 years of diagnosis. There was a significant improvement in 5-year survival from 32.0% prior to 1977 to 91.0% for patients diagnosed between 1997 and 2006. SBP and DBP improved significantly during follow-up (P < 0.0001). Multivariate analyses revealed that age, decade of MHT diagnosis, baseline creatinine, and follow-up SBP were independent predictors of survival (all P < 0.0001). Conclusions Demography and number of new cases of MHT have not changed dramatically over the past 40 years. Five-year post-MHT survival has improved significantly, possibly related to lower BP targets, tighter BP control, and availability of new classes of antihypertensive drugs. American Journal of Hypertension 2009; 22:1199–1204 © 2009 American Journal of Hypertension, Ltd
Journal Article
Hypertension in ethnic groups: epidemiological and clinical perspectives
In the UK and other developed nations, hypertension and its vascular complications are more common in ethnically African and South-Asian communities compared with Europeans. While these conditions are less common in rural India and Africa, they present a rising problem in expanding cities in all developing countries. Hypertension is, therefore, mainly related to environmental and lifestyle factors rather than genetically determined racial differences. Studies in the USA and elsewhere show that the striking differences in the prevalence of hypertension between people of African and European origin are greatly reduced after adjustment for socio-economic status. One important and probably genuine racial difference between ethnic groups is the significantly suppressed activity of the renin-angiotensin-aldosterone system in African-origin hypertensive patients. As a consequence of this, they are rather more sensitive to a low-salt diet but significantly less sensitive to drugs that block the renin-angiotensin-aldosterone system (angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers) and β-blockers. There is also evidence that renin suppression is common in Japanese and Chinese hypertensive patients as well, although no direct comparisons between these two groups with European-origin patients have been carried out. The management and control of hypertension is unsatisfactory in all ethnic groups and all nations. No one group needs particular targeting; all need better quality systematic care.
Journal Article
Management of hypertension in ethnic minorities
Randomised controlled trials have shown that diuretics reduce hypertension related morbidity and mortality in black as well as in white populations, but there is evidence of a greater decrease in blood pressure among hypertensive black patients when compared to white patients when they receive an equivalent dose of a diuretic. 19 Hydrochlorothiazide in a dosage of 12.5-25.0 mg daily is a good choice but, if the concentration of serum creatinine is 2 mg/dl (177 µmol/l) or more, thiazide diuretics are usually ineffective, and a loop-type diuretic should be substituted. 20 Calcium channel blockers are also extremely effective antihypertensive drugs in black patients. 21 Response of whites and blacks to differing antihypertensive medication: Management of hypertension in patients from ethnic minorities: key points In a western adult population the prevalence of hypertension exceeds 20% Hypertension is a major risk factor for cardiovascular and cerebrovascular disease The pathophysiology of hypertension differs in black adults compared to South Asians and whites South Asians appear to respond to antihypertensive drug treatment in a similar manner to whites There is excellent blood pressure lowering efficacy of diuretics and calcium channel antagonists in hypertensive black patients ACE inhibitors, β blockers, and angiotensin receptor antagonists are generally less effective as monotherapy in black hypertensives CONCLUSION Hypertension is associated with significant morbidity and mortality, some of which can be reduced with effective blood pressure lowering.
Journal Article