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Background: Statin therapy is effective for the prevention of atherosclerotic cardiovascular disease and is widely prescribed, but there are persisting concerns that statin therapy might frequently cause muscle pain or weakness. We aimed to address these through an individual participant data meta-analysis of all recorded adverse muscle events in large, long-term, randomised, double-blind trials of statin therapy. Methods: Randomised trials of statin therapy were eligible if they aimed to recruit at least 1000 participants with a scheduled treatment duration of at least 2 years, and involved a double-blind comparison of statin versus placebo or of a more intensive versus a less intensive statin regimen. We analysed individual participant data from 19 double-blind trials of statin versus placebo (n=123 940) and four double-blind trials of a more intensive versus a less intensive statin regimen (n=30 724). Standard inverse-variance-weighted meta-analyses of the effects on muscle outcomes were conducted according to a prespecified protocol. Findings: Among 19 placebo-controlled trials (mean age 63 years [SD 8], with 34 533 [27·9%] women, 59 610 [48·1%] participants with previous vascular disease, and 22 925 [18·5%] participants with diabetes), during a weighted average median follow-up of 4·3 years, 16 835 (27·1%) allocated statin versus 16 446 (26·6%) allocated placebo reported muscle pain or weakness (rate ratio [RR] 1·03; 95% CI 1·01–1·06). During year 1, statin therapy produced a 7% relative increase in muscle pain or weakness (1·07; 1·04–1·10), corresponding to an absolute excess rate of 11 (6–16) events per 1000 person-years, which indicates that only one in 15 ([1·07–1·00]/1·07) of these muscle-related reports by participants allocated to statin therapy were actually due to the statin. After year 1, there was no significant excess in first reports of muscle pain or weakness (0·99; 0·96–1·02). For all years combined, more intensive statin regimens (ie, 40–80 mg atorvastatin or 20–40 mg rosuvastatin once per day) yielded a higher RR than less intensive or moderate-intensity regimens (1·08 [1·04–1·13] vs 1·03 [1·00–1·05]) compared with placebo, and a small excess was present (1·05 [0·99–1·12]) for more intensive regimens after year 1. There was no clear evidence that the RR differed for different statins, or in different clinical circumstances. Statin therapy yielded a small, clinically insignificant increase in median creatine kinase values of approximately 0·02 times the upper limit of normal. Interpretation: Statin therapy caused a small excess of mostly mild muscle pain. Most (>90%) of all reports of muscle symptoms by participants allocated statin therapy were not due to the statin. The small risks of muscle symptoms are much lower than the known cardiovascular benefits. There is a need to review the clinical management of muscle symptoms in patients taking a statin. Funding: British Heart Foundation, Medical Research Council, Australian National Health and Medical Research Council.

Background The extent of coronary disease affects clinical outcomes and may predict the effectiveness of coronary revascularization with either coronary artery bypass graft (CABG) surgery or percutaneous coronary intervention (PCI). The SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) score quantifies the extent of coronary disease. Objectives This study sought to determine whether SYNTAX scores predicted outcomes and the effectiveness of coronary revascularization compared with medical therapy in the BARI-2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial. Methods Baseline SYNTAX scores were retrospectively calculated for BARI-2D patients without prior revascularization (N = 1,550) by angiographic laboratory investigators masked to patient characteristics and outcomes. The primary outcome was major cardiovascular events (a composite of death, myocardial infarction, and stroke) over 5 years. Results A mid/high SYNTAX score (≥23) was associated with a higher risk of major cardiovascular events (hazard ratio: 1.36, confidence interval: 1.07 to 1.75, p = 0.01). Patients in the CABG stratum had significantly higher SYNTAX scores: 36% had mid/high SYNTAX scores compared with 13% in the PCI stratum (p Conclusions Among patients with diabetes and stable ischemic heart disease, higher SYNTAX scores predict higher rates of major cardiovascular events and were associated with more favorable outcomes of revascularization compared with medical therapy among patients suitable for CABG. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes; NCT00006305)

The ECG has been recorded in patients with vasoregulatory asthenia, coronary insufficiency and arterial hypertension, as well as in healthy controls at rest, after hyperventilation, during an orthostatic test and a work test. S-T and T depressions, usually of sympathicotonic type, appeared or were accentuated after hyperventilation, particularly in patients with vasoregulatory asthenia, who also showed similar changes during an orthostatic test. Such ECG changes were uncommon in the other groups. The results sustain the concept that an increased sympathetic autonomic nervous tone provoked by hyperventilation causes the S-T and T depressions, particularly in patients with vasoregulatory asthenia. The diagnostic value of the hyperventilation ECG for analysing functional S-T and T depressions is emphasized, as well as the diagnostic difficulties in the evaluation of ECG changes in patients who hyperventilate, for instance during a hypoxia test.

The effect of a number of repeated work tests on different electrocardiographic ST and T changes has been studied and the effect compared with that after an adrenergic beta-receptor blockade. In subjects with different ECG changes but without any apparent organic heart disease there was a normalization of the ST and T changes during the period of repeated work tests. The normalizing effect was almost identical to that after adrenergic blockade. Different patterns of ST and especially T depressions on the ECG at rest, in the standing position and during and after work are described. In patients with organic heart diseases the repeated work tests generally had no effect on the ECG patterns typical of coronary insufficiency and myocarditis. In one patient with signs of a vasoregulatory disturbance there seemed to be ST and T changes of different origin, probably both functional and organic. The effect of the adrenergic blockade was almost identical to that of the repeated work tests. The study gives support to the results of a previous investigation in which the possibility of using an adrenergic blockade for differentiating between ECG changes of functional and organic origin was pointed out. The normalization effect of 4–6 work tests over a period of 4–6 days on functional ST and T changes on the ECG is supposed to be due to a physical and psychic adaptation to the work tests and to the examination situation.

Background: Prior randomized trials of hypertension have rarely examined patient heterogeneity in response to treatments and the implications for outcomes. Methods: We applied growth mixture modeling to identify distinct SBP trajectory classes within the first 6 months of ALLHAT. We assessed the

To evaluate the risk of incident physical disability and the decline in gait speed over a 6-year follow-up associated with a low ankle-arm index (AAI) in older adults.Observational cohort study.Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Allegheny County, Pennsylvania.Four thousand seven hundred five older adults, 58% women and 17.6% black, participating in the Cardiovascular Health Study.AAI was measured in 1992/93 (baseline). Self-reported mobility, activity of daily living (ADL), and instrumental activity of daily living (IADL) disability and gait speed were recorded at baseline and at 1-year intervals over 6 years of follow-up. Mobility disability was defined as any difficulty walking half a mile and ADL and IADL disability was defined as any difficulty with 11 specific ADL and IADL tasks. Individuals with mobility, ADL, or IADL disability at baseline were excluded from the respective incident disability analyses.Lower baseline AAI values were associated with increased risk of mobility disability and ADL/IADL disability. Clinical cardiovascular disease (CVD), diabetes mellitus, and interim CVD events partially explained these associations for mobility disability and clinical CVD and diabetes mellitus partially explained these associations for ADL and IADL disability. Individuals with an AAI less than 0.9 had on average a mean decrease in gait speed of 0.02 m/s per year, or a decline of 0.12 m/s over the 6-year follow-up. Prevalent CVD partly explained this decrease but interim CVD events did not further attenuate it.Low AAI serves as marker of future disability risk. Reduction of disability risk in patients with a low AAI should consider cardiovascular comorbidity and the prevention of additional disabling CVD events.

To analyze baseline data from the Ginkgo Evaluation of Memory (GEM) study, in which information was collected on the use of all dietary supplements.Cross-sectional regression analysis.GEM study sites in California, Maryland, North Carolina, and Pennsylvania.The GEM study enrolled 3,072 ambulatory individuals aged 75 and older between September 2000 and June 2002.Self-reported use of dietary supplements and use identified through bottles brought to the clinic.Respectively, 59.4%, 66.6%, and 27.4% of the GEM study cohort used a multivitamin, at least one individual vitamin or mineral supplement, and some type of nonvitamin/nonmineral dietary supplement (NVNMDS). In logistic regression models, multivitamin use was associated with female sex, a higher income, a higher modified Mini-Mental State Examination score, difficulty with mobility, and asthma history; use of any other vitamin or mineral was associated with female sex, white race, nonsmoking, more years of schooling, difficulty walking, a history of osteoporosis, and reading health and senior magazines; and NVNMDS use was associated with residing in California, having difficulties with muscle strength, and reading health and senior magazines.There were substantial differences between individuals who used vitamins and minerals and those who used NVNMDS. These data require that trial investigators pay close attention to participant use of off-protocol dietary supplements. In addition, these findings may help identify elderly individuals likely to combine NVNMDS and prescription drugs.

The Heart and Estrogen/progestin Replacement Study (HERS) was a randomized trial of estrogen plus progestin therapy after menopause.To examine the effect of long-term postmenopausal hormone therapy on common noncardiovascular disease outcomes.Randomized, blinded, placebo-controlled trial of 4.1 years' duration (HERS) and subsequent open-label observational follow-up for 2.7 years (HERS II), carried out between 1993 and 2000 in outpatient and community settings at 20 US clinical centers.A total of 2763 postmenopausal women with coronary disease and average age of 67 years at enrollment in HERS; 2321 women (93% of those surviving) consented to follow-up in HERS II.Participants were randomly assigned to receive 0.625 mg/d of conjugated estrogens plus 2.5 mg of medroxyprogesterone acetate (n = 1380) or placebo (n = 1383) during HERS; open-label hormone therapy was prescribed at personal physicians' discretion during HERS II. The proportions with at least 80% adherence to hormones declined from 81% (year 1) to 45% (year 6) in the hormone group and increased from 0% (year 1) to 8% (year 6) in the placebo group.Thromboembolic events, biliary tract surgery, cancer, fracture, and total mortality.Comparing women assigned to hormone therapy with those assigned to placebo, the unadjusted intention-to-treat relative hazard (RH) for venous thromboembolism declined from 2.66 (95% confidence interval [CI], 1.41-5.04) during HERS to 1.40 (95% CI, 0.64-3.05) during HERS II (P for time trend =.08); it was 2.08 overall for the 6.8 years (95% CI, 1.28-3.40), and 3 of the 73 women with thromboembolism died within 30 days due to pulmonary embolism. The overall RH for biliary tract surgery was 1.48 (95% CI, 1.12-1.95); for any cancer, 1.19 (95% CI, 0.95-1.50); and for any fracture, 1.04 (95% CI, 0.87-1.25). There were 261 deaths among those assigned to hormone therapy and 239 among those assigned to placebo (RH, 1.10; 95% CI, 0.92-1.31). Adjusted and as-treated analyses did not alter our conclusions.Treatment for 6.8 years with estrogen plus progestin in older women with coronary disease increased the rates of venous thromboembolism and biliary tract surgery. Trends in other disease outcomes were not favorable and should be assessed in larger trials and in broader populations.

Furberg, C. and Hornell, H. (Department of Clinical Physiology and Paediatrics, Central Hospital, Boden, Sweden). Familial QT prolongation and risk of sudden death. Acta Paediatr Scand, 64:777, 1975.–Two sisters with the syndrome of familial QT prolongation in the ECG and syncope are presented. A recently suggested mechanism of the syndrome is presented and preventive measures to reduce the risk of sudden death associated with it are proposed.

UNLABELLED All cases of acute myocardial infarction (AMI) and sudden death due to coronary heart disease have been registered in two Swedish and two Finnish cities during a 1-year period. The incidence increased steeply with age in both sexes and was in all age groups far higher in males than in females. The age-related incidence in both Finnish cities was definitely higher than in Gothenburg, Sweden, while the other Swedish register city, Boden, had an intermediate position. THE CASE fatality rate within one year was 44.2% for males and 37.4% for females. This difference was already apparent in the first hour after the onset of the attack, when the case: fatality rate was 15.5% for males and 9.3% for females. A history of previous cardiovascular disease was much more common in AMI patients than in the general population. It was also slightly more common in subjects who died suddenly than in AMI patients who did not die suddenly.

IT is known that adrenaline accelerates glycogenolysis in liver and in muscles, which leads to an elevation of the concentration of blood sugar and blood lactate1. During work (and especially with high work loads) there is a substantial increase in the concentration of blood lactate, which is mainly produced in the working muscles2. This can in part arise from increased adrenergic activity during work. The purpose of the present investigation was to test this assumption by means of an adrenergic beta-blocking agent.

The antihypertensive effect of a new beta-adrenergic blocking agent, Aptin, has been studied in a group of 12 patients with moderate arterial hypertension. The trial was carried out using a conventional double-blind cross-over design. A significant reduction of 18 mm Hg in the systolic blood pressure at rest was recorded for the entire group. The corresponding decrease of 7 mm Hg in the distolic pressure was not significant. During exercise a more pronounced reduction was recorded than at rest. The correlation found between the reduction in systolic blood pressure and heart rate during exercise during the Aptin treatment was probably significant. The antihypertensive effect of Aptin was considered as moderate. The drug may be of therapeutic value in combination with other antihypertensive drugs. No significant adverse effects or changes in results of laboratory tests were noted during the Aptin treatment.