274 research outputs found
MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomised placebocontrolled trial
No full textBackground: Throughout the usual LDL cholesterol range in Western populations, lower blood concentrations are associated with lower cardiovascular disease risk. In such populations, therefore, reducing LDL cholesterol may reduce the development of vascular disease, largely irrespective of initial cholesterol concentrations. Methods: 20 536 UK adults (aged 40–80 years) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive 40 mg simvastatin daily (average compliance: 85%) or matching placebo (average non-study statin use: 17%). Analyses are of the first occurrence of particular events, and compare all simvastatin-allocated versus all placebo-allocated participants. These “intention-to-treat” comparisons assess the effects of about two-thirds (85% minus 17%) taking a statin during the scheduled 5-year treatment period, which yielded an average difference in LDL cholesterol of 1·0 mmol/L (about two-thirds of the effect of actual use of 40 mg simvastatin daily). Primary outcomes were mortality (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. Findings: All-cause mortality was significantly reduced (1328 [12·9%] deaths among 10 269 allocated simvastatin versus 1507 [14·7%] among 10 267 allocated placebo; p=0·0003), due to a highly significant 18% (SE 5) proportional reduction in the coronary death rate (587 [5·7%] vs 707 [6·9%]; p=0·0005), a marginally significant reduction in other vascular deaths (194 [1·9%] vs 230 [2·2%]; p=0·07), and a non-significant reduction in non-vascular deaths (547 [5·3%] vs 570 [5·6%]; p=0·4). There were highly significant reductions of about one-quarter in the first event rate for nonfatal myocardial infarction or coronary death (898 [8·7%] vs 1212 [11·8%]; p<0·0001), for non-fatal or fatal stroke (444 [4·3%] vs 585 [5·7%]; p<0·0001), and for coronary or noncoronary revascularisation (939 [9·1%] vs 1205 [11·7%]; p<0·0001). For the first occurrence of any of these major vascular events, there was a definite 24% (SE 3; 95% CI 19–28) reduction in the event rate (2033 [19·8%] vs 2585 [25·2%] affected individuals; p<0·0001). During the first year the reduction in major vascular events was not significant, but subsequently it was highly significant during each separate year. The proportional reduction in the event rate was similar (and significant) in each subcategory of participant studied, including: those without diagnosed coronary disease who had cerebrovascular disease, or had peripheral artery disease, or had diabetes; men and, separately, women; those aged either under or over 70 years at entry; and—most notably—even those who presented with LDL cholesterol below 3·0 mmol/L (116 mg/dL), or total cholesterol below 5·0 mmol/L (193 mg/dL). The benefits of simvastatin were additional to those of other cardioprotective treatments. The annual excess risk of myopathy with this regimen was about 0·01%. There were no significant adverse effects on cancer incidence or on hospitalisation for any other non-vascular cause. Interpretation: Adding simvastatin to existing treatments safely produces substantial additional benefits for a wide range of high-risk patients, irrespective of their initial cholesterol concentrations. Allocation to 40 mg simvastatin daily reduced the rates of myocardial infarction, of stroke, and of revascularisation by about one-quarter. After making allowance for non-compliance, actual use of this regimen would probably reduce these rates by about one-third. Hence, among the many types of high-risk individual studied, 5 years of simvastatin would prevent about 70–100 people per 1000 from suffering at least one of these major vascular events (and longer treatment should produce further benefit). The size of the 5-year benefit depends chiefly on such individuals' overall risk of major vascular events, rather than on their blood lipid concentrations alone
Prior events predict cerebrovascular and coronary outcomes in the PROGRESS trial
No full text<p><b>Background and Purpose:</b> The relationship between baseline and recurrent vascular events may be important in the targeting of secondary prevention strategies. We examined the relationship between initial event and various types of further vascular outcomes and associated effects of blood pressure (BP)–lowering.</p>
<p><b>Methods:</b> Subsidiary analyses of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial that established the benefits of BP–lowering in 6105 patients (mean age 64 years, 30% female) with cerebrovascular disease, randomly assigned to either active treatment (perindopril for all, plus indapamide in those with neither an indication for, nor a contraindication to, a diuretic) or placebo(s).</p>
<p><b>Results:</b> Stroke subtypes and coronary events were associated with 1.5- to 6.6-fold greater risk of recurrence of the same event (hazard ratios, 1.51 to 6.64; P=0.1 for large artery infarction, P<0.0001 for other events). However, 46% to 92% of further vascular outcomes were not of the same type. Active treatment produced comparable reductions in the risk of vascular outcomes among patients with a broad range of vascular events at entry (relative risk reduction, 25%; P<0.0001 for ischemic stroke; 42%, P=0.0006 for hemorrhagic stroke; 17%, P=0.3 for coronary events; P homogeneity=0.4).</p>
<p><b>Conclusions:</b> Patients with previous vascular events are at high risk of recurrences of the same event. However, because they are also at risk of other vascular outcomes, a broad range of secondary prevention strategies is necessary for their treatment. BP–lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction.</p>
C-reactive protein concentration and the vascular benefits of statin therapy: an analysis of 20 536 patients in the Heart Protection Study
No full textSummaryBackgroundIt has been suggested that inflammation status, as assessed by C-reactive protein (CRP) concentration, modifies the vascular protective effects of statin therapy. In particular, there have been claims that statins might be more beneficial in people with raised CRP concentrations, and might even be ineffective in people with low concentrations of both CRP and LDL cholesterol. This study aimed to test this hypothesis.MethodsIn 69 UK hospitals, 20 536 men and women aged 40–80 years at high risk of vascular events were randomly assigned to simvastatin 40 mg daily versus matching placebo for a mean of 5·0 years. Patients were categorised into six baseline CRP groups (<1·25, 1·25–1·99, 2·00–2·99, 3·00–4·99, 5·00–7·99, and ≥8·00 mg/L). The primary endpoint for subgroup analyses was major vascular events, defined as the composite of coronary death, myocardial infarction, stroke, or revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN48489393.FindingsOverall, allocation to simvastatin resulted in a significant 24% (95% CI 19–28) proportional reduction in the incidence of first major vascular event after randomisation (2033 [19·8%] allocated simvastatin vs 2585 [25·2%] allocated placebo). There was no evidence that the proportional reduction in this endpoint, or its components, varied with baseline CRP concentration (trend p=0·41). Even in participants with baseline CRP concentration less than 1·25 mg/L, major vascular events were significantly reduced by 29% (99% CI 12–43, p<0·0001; 239 [14·1%] vs 329 [19·4%]). No significant heterogeneity in the relative risk reduction was recorded between the four subgroups defined by the combination of low or high baseline concentrations of LDL cholesterol and CRP (p=0·72). In particular, there was clear evidence of benefit in those with both low LDL cholesterol and low CRP (27% reduction, 99% CI 11–40, p<0·0001; 295 [15·6%] vs 400 [20·9%]).InterpretationEvidence from this large-scale randomised trial does not lend support to the hypothesis that baseline CRP concentration modifies the vascular benefits of statin therapy materially.FundingUK Medical Research Council, British Heart Foundation, Merck, Roche Vitamins, and GlaxoSmithKline
Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular outcomes in 20,536 people with peripheral arterial disease and other high-risk conditions
No full textObjectives The Heart Protection Study (HPS) provides an opportunity to assess directly the effects of cholesterol-lowering therapy on major vascular events (defined as myocardial infarction, coronary death, stroke, or revascularization) in patients with peripheral arterial disease (PAD). In addition, the effects on peripheral vascular events (ie, non-coronary revascularization, aneurysm repairs, major amputations or PAD deaths) can be assessed. Methods 6748 UK adults with PAD and 13,788 other high-risk participants were randomly allocated to receive 40 mg simvastatin daily or matching placebo, yielding an average LDL cholesterol difference of 1.0 mmol/L (39 mg/dL) during a mean of 5 years. Results For participants with PAD, allocation to simvastatin was associated with a highly significant 22% (95% CI 15-29) relative reduction in the rate of first major vascular event following randomisation (895 [26.4%] simvastatin-allocated vs 1101 [32.7%] placebo-allocated; P < .0001), which was similar to that seen among the other high-risk participants. The absolute reduction in first major vascular event was 63 (SE 11) per 1000 patients with PAD and 50 (SE 7) per 1000 without pre-existing PAD. Overall, among all participants, there was a 16% (5-25) relative reduction in the rate of first peripheral vascular event following randomisation (479 [4.7%] simvastatin vs 561 [5.5%] placebo), largely irrespective of baseline LDL cholesterol and other factors. This effect chiefly reflects a 20% (8-31) relative reduction in non-coronary revascularization procedures (334 [3.3%] vs 415 [4.0%]; P = .002). Conclusion HPS demonstrates the benefits of cholesterol-lowering statin therapy in patients with PAD, regardless of their presenting cholesterol levels and other presenting features. Allocation to 40 mg simvastatin daily reduces the rate of first major vascular events by about one-quarter, and that of peripheral vascular events by about one-sixth, with large absolute benefits seen in participants with PAD because of their high vascular risk. Consequently, statin therapy should be considered routinely for all patients with PAD.(J Vasc Surg 2007;45:645-54.
MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20 536 high-risk individuals: a randomised placebo-controlled trial
No full textBackground It has been suggested that increased intake of various antioxidant vitamins reduces the incidence rates of vascular disease, cancer, and other adverse outcomes. Methods 20 536 UK adults (aged 40–80) with coronary disease, other occlusive arterial disease, or diabetes were randomly allocated to receive antioxidant vitamin supplementation (600 mg vitamin E, 250 mg vitamin C, and 20 mg β-carotene daily) or matching placebo. Intention-to-treat comparisons of outcome were conducted between all vitamin-allocated and all placebo-allocated participants. An average of 83% of participants in each treatment group remained compliant during the scheduled 5-year treatment period. Allocation to this vitamin regimen approximately doubled the plasma concentration of α-tocopherol, increased that of vitamin C by one-third, and quadrupled that of β-carotene. Primary outcomes were major coronary events (for overall analyses) and fatal or non-fatal vascular events (for subcategory analyses), with subsidiary assessments of cancer and of other major morbidity. Findings There were no significant differences in all-cause mortality (1446 [14·1%] vitamin-allocated vs 1389 [13·5%] placebo-allocated), or in deaths due to vascular (878 [8·6%] vs 840 [8·2%]) or non-vascular (568 [5·5%] vs 549 [5·3%]) causes. Nor were there any significant differences in the numbers of participants having non-fatal myocardial infarction or coronary death (1063 [10·4%] vs 1047 [10·2%]), non-fatal or fatal stroke (511 [5·0%] vs 518 [5·0%]), or coronary or non-coronary revascularisation (1058 [10·3%] vs 1086 [10·6%]). For the first occurrence of any of these “major vascular events”, there were no material differences either overall (2306 [22·5%] vs 2312 [22·5%]; event rate ratio 1·00 [95% CI 0·94–1·06]) or in any of the various subcategories considered. There were no significant effects on cancer incidence or on hospitalisation for any other non-vascular cause. Interpretation Among the high-risk individuals that were studied, these antioxidant vitamins appeared to be safe. But, although this regimen increased blood vitamin concentrations substantially, it did not produce any significant reductions in the 5-year mortality from, or incidence of, any type of vascular disease, cancer, or other major outcome
The effects of cholesterol lowering with simvastatin on cause-specific mortality and on cancer incidence in 20,536 high-risk people: a randomised placebo-controlled trial [ISRCTN48489393].
No full textBACKGROUND: There have been concerns that low blood cholesterol concentrations may cause non-vascular mortality and morbidity. Randomisation of large numbers of people to receive a large, and prolonged, reduction in cholesterol concentrations provides an opportunity to address such concerns reliably. METHODS: 20,536 UK adults (aged 40-80 years) with vascular disease or diabetes were randomly allocated to receive 40 mg simvastatin daily or matching placebo. Prespecified safety analyses were of cause-specific mortality, and of total and site-specific cancer incidence. Comparisons between all simvastatin-allocated versus all placebo-allocated participants (ie, "intention-to-treat") involved an average difference in blood total cholesterol concentration of 1.2 mmol/L (46 mg/dL) during the scheduled 5-year treatment period. RESULTS: There was a highly significant 17% (95% CI 9-25) proportional reduction in vascular deaths, along with a non-significant reduction in all non-vascular deaths, which translated into a significant reduction in all-cause mortality (p = 0.0003). The proportional reduction in the vascular mortality rate was about one-sixth in each subcategory of participant studied, including: men and women; under and over 70 years at entry; and total cholesterol below 5.0 mmol/L or LDL cholesterol below 3.0 mmol/L. No significant excess of non-vascular mortality was observed in any subcategory of participant (including the elderly and those with pretreatment total cholesterol below 5.0 mmol/L), and there was no significant excess in any particular cause of non-vascular mortality. Cancer incidence rates were similar in the two groups, both overall and in particular subcategories of participant, as well as at particular primary sites. There was no suggestion that any adverse trends in non-vascular mortality or morbidity were beginning to emerge with more prolonged treatment. CONCLUSION: These findings, which are based on large numbers of deaths and non-fatal cancers, provide considerable reassurance that lowering total cholesterol concentrations by more than 1 mmol/L for an average of 5 years does not produce adverse effects on non-vascular mortality or cancer incidence. Moreover, among the many different types of high-risk individual studied, simvastatin 40 mg daily consistently produced substantial reductions in vascular (and, hence, all-cause) mortality, as well as in the rates of non-fatal heart attacks, strokes and revascularisation procedures
Weight loss in a cardiovascular trial population identifies people at future risk of dementia
No full textINTRODUCTION: Populations at increased risk of dementia need to be identified for well‐powered trials of preventive interventions. Weight loss, which often occurs in pre‐clinical dementia, could identify a population at sufficiently high dementia risk. METHODS: In 12,975 survivors in the Heart Protection Study statin trial of people with, or at high risk of, cardiovascular disease, the association of weight change over 5 years during the trial with post‐trial dementia recorded in electronic hospital admission and death records (n = 784) was assessed, after adjustment for age, sex, treatment allocation, and deprivation measures. RESULTS: Among the 60% without substantial weight gain (≤2 kg weight gain), each 1 kg weight loss was associated with a risk ratio for dementia of 1.04 (95% confidence interval, 1.02–1.07). Weight loss ≥4 kg and cognitive function below the mean identified participants aged ≥67 years with a 13% 10‐year dementia risk. DISCUSSION: The combination of weight loss and high vascular risk identified individuals at high risk of dementia who could be recruited to dementia prevention trials
Lipoprotein-associated phospholipase A₂ activity and mass in relation to vascular disease and nonvascular mortality.
No full textOBJECTIVES: To assess whether associations of circulating lipoprotein-associated phospholipase A₂ (Lp-PLA₂) with vascular disease are independent of other risk factors. METHODS: Lp-PLA₂ activity and mass, lipids and other characteristics were measured at baseline in 19,037 individuals at high risk of vascular disease in a randomized trial of simvastatin with 5-year average follow-up. RESULTS: Lp-PLA₂ activity and mass were correlated with each other (r = 0.56), lipids and other vascular risk factors. The moderate association of Lp-PLA₂ activity with occlusive coronary events (n = 2531) in analyses adjusted for nonlipid factors (hazard ratio per 1 SD [HR] 1.11, 95% CI 1.06-1.15) became nonsignificant after further adjustment for apolipoproteins (HR 1.02, 0.97-1.06). Such adjustment also attenuated HRs with Lp-PLA₂ mass from 1.08 (1.03-1.12) to 1.05 (1.01-1.09). By contrast, the HR with apolipoprotein-B100 of 1.15 (1.10-1.19) was only slightly attenuated to 1.14 (1.09-1.19) after further adjustment for apolipoprotein A₁ and Lp-PLA₂. Age- and sex-adjusted HRs for other cardiac events (n = 1007) with either Lp-PLA₂ activity or mass were about 1.20, but HRs reduced after adjustment for nonlipid factors (activity: 1.11, 1.04-1.18; mass: 1.08, 1.02-1.15). Adjusted HRs for ischaemic stroke (n = 900) were weak and nonsignificant and for nonvascular mortality (n = 1040) were 1.01 (0.94-1.09) with activity and 1.12 (1.05-1.19) with mass. Simvastatin reduced Lp-PLA₂ levels by about one-quarter, but simvastatin's vascular protection did not vary with baseline Lp-PLA₂ concentration. CONCLUSIONS: Associations of Lp-PLA₂ with occlusive coronary events depend considerably on lipid levels, whereas those with other cardiac events appear to reflect confounding from cardiovascular medication and prior vascular disease
N-terminal Pro-B-type natriuretic peptide, vascular disease risk, and cholesterol reduction among 20,536 patients in the MRC/BHF heart protection study.
No full textOBJECTIVES: We sought to assess the ability of N-terminal pro-B-type natriuretic peptide (N-BNP) to predict vascular events in high-risk people and to test whether statins benefit people with high levels of N-BNP. BACKGROUND: The predictive value of N-BNP for occlusive vascular events and the effects of statins in people with high N-BNP levels are uncertain. METHODS: A total of 20,536 people were assigned randomly to simvastatin 40 mg daily or placebo for an average of 5 years. Five baseline N-BNP groups were defined ( andlt; 386; 386 to 1,171; 1,172 to 2,617; 2,618 to 5,758; and > or =5,759 pg/ml). RESULTS: Baseline N-BNP was strongly predictive of future vascular events independently of other characteristics. Compared with participants with N-BNP andlt; 386 pg/ml, those with levels > or =5,759 pg/ml had adjusted relative risks for major vascular events (MVEs) (i.e., major coronary events [MCE] [nonfatal myocardial infarction or coronary death], stroke, or revascularization) of 2.26, for MCE of 3.09, for stroke of 1.80, and for heart failure (hospitalization or death) of 9.23 (all p andlt; 0.0001). Overall, simvastatin allocation reduced the relative risk of MVE by 24% (95% confidence interval 19 to 28). There was a trend toward smaller (but still significant) proportional reductions in MVE among participants with greater baseline N-BNP levels, but the absolute benefits of simvastatin allocation were similar at all N-BNP levels. Simvastatin allocation was also associated with a 14% (95% confidence interval 0 to 25) proportional reduction in heart failure. No excess risk of other vascular and nonvascular outcomes was observed with simvastatin allocation among participants with greater baseline values of N-BNP. CONCLUSIONS: In this study, N-BNP levels were strongly predictive not only of heart failure but also of MVEs. In people with high N-BNP levels consistent with heart failure, statin allocation significantly reduced vascular risk, with no evidence of hazard. (http://www.controlledtrials.com/ISRCTN48489393/48489393)
Prevalence, incidence, primary care burden and medical treatment of angina in Scotland: age, sex and socioeconomic disparities: a population-based study
No full textObjective: To examine the epidemiology, primary care burden and treatment of angina in Scotland.
Design: Cross-sectional data from primary care practices participating in the Scottish continuous morbidity recording scheme between 1 April 2001 and 31 March 2002.
Setting: 55 primary care practices (362 155 patients).
Participants: 9508 patients with angina.
Results: The prevalence of angina in Scotland was 28/1000 in men and 25/1000 in women (p < 0.05) and increased with age. The prevalence of angina also increased with increasing socioeconomic deprivation from 18/1000 in the least deprived category to 31/1000 in the most deprived group (p < 0.001 for trend). The incidence of angina was higher in men (1.8/1000) than in women (1.4/1000) (p = 0.004) and increased with increasing age and socioeconomic deprivation. Socioeconomically deprived patients (0.48 contacts/patient among the most deprived) were less likely than affluent patients (0.58 contacts/patient among the least deprived) to see their general practitioner on an ongoing basis p = 0.006 for trend). Among men, 52% were prescribed ß blockers, 44% calcium channel blockers, 72% aspirin, 54% statins and 36% angiotensin converting enzyme inhibitors or angiotensin receptor blockers. The corresponding prescription rates for women were 46% (p < 0.001), 41% (p = 0.02), 69% (p < 0.001), 45% (p < 0.001) and 30% (p < 0.001). Among patients < 75 years old 52% were prescribed a β blocker and 58% a statin. The corresponding figures for patients ≥ 75 years were 42% (p < 0.001) and 31% (p < 0.001).
Conclusions: Angina is a common condition, more so in men than in women. Socioeconomically deprived patients are more likely to have angina but are less likely to consult their general practitioner. Guideline-recommended treatments for angina are underused in women and older patients. These suboptimal practice patterns, which are worst in older women, are of particular concern, as in Scotland more women (and particularly older women) than men have angina
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