Mental stress, atheroma, myocardial ischaemia and injury: the link is inflammation.

Increasing observational and experimental trial data have shown that mental stress can lead to an increase in adverse clinical cardiovascular events. Mental stress affects the heart by inducing ischaemia and precipitating myocardial infarction (MI) or direct myocardial injury. Mental stress leads to systemic inflammation. Inflammation is known to cause rapid atheromatous plaque progression, instability and thrombosis-the classic type 1 MI. Inflammation can also lead to type 2 MI or myocarditis and injury. The published data linking systemic inflammation, mental stress and cardiovascular disease will be reviewed to establish the linkage between mind and heart, thereby highlighting the importance of holistically managing the patient, not only addressing separate organ systems. Finally, recent trial evidence showing the value of anti-inflammatory drugs in cardiovascular and mental conditions will be briefly considered.

Angiotensin-Converting Enzyme Inhibitors (ACEIs) and Angiotensin-Receptor Blockers (ARBs) in Patients at High Risk of Cardiovascular Events: A Meta-Analysis of 10 Randomised Placebo-Controlled Trials.

Context. Whether angiotensin converting-enzyme inhibitors (ACEI) and angiotensin-receptor blockers (ARB) are useful in high risk patients without heart failure is unclear. We perform a meta-analysis of prospective randomized placebo-controlled ACEI or ARB trials studying patients with a combination of risk factors to assess treatment impact on all cause mortality, cardiovascular mortality, nonfatal myocardial infarction (MI) and stroke. Method. A PubMed search was made for placebo-controlled trials recruiting at least 1,200 high risk patients randomized to either ACEI or ARB, with follow-up of at least 2 years. Meta-analysis was performed using the RevMan 5 program and Mantel-Haenszel analysis was done with a fixed effects model. Results. Ten trials recruiting 77,633 patients were reviewed. All cause mortality was significantly reduced by ACEI (RR 0.89; P = 0.0008), but not by ARB treatment (RR 1.00; P = 0.89). Cardiovascular mortality and nonfatal MI were also reduced in the ACEI trials but not with ARB therapy. Stroke was significantly reduced in the ACEI trials (RR 0.75; P < 0.00001) and more modestly reduced in the ARB trials (RR 0.90; P = 0.01). Conclusion. ACEI treatment reduced stroke, nonfatal MI, cardiovascular and total mortality in high risk patients, while ARB modestly reduced stroke with no effect on nonfatal MI, cardiovascular and total mortality.

Are angiotensin-converting enzyme inhibitors and angiotensin receptor blockers especially useful for cardiovascular protection?

PURPOSE: This article seeks to objectively review the clinical trial evidence to determine whether angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) have special cardiovascular protective effects. METHODS: An objective review of the clinical trial evidence. RESULTS: Clinical trials in hypertensive patients comparing ACEI and ARB with other drugs generally showed no difference in the primary cardiovascular outcome (United Kingdom Prospective Diabetes Study Group, Captopril Prevention Project, Swedish Trial in Old Patients with Hypertension 2, Japan Multicenter Investigation for Cardiovascular Diseases-B Randomized Trial, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, Second Australian National Blood Pressure Study Group, Valsartan Antihypertensive Long-Term Use Evaluation). Where the primary, or major secondary, cardiovascular end-point favors one of the treatment arms, it was always the arm with the lower achieved blood pressure that saw the better clinical result as in Losartan Intervention For Endpoint Reduction in Hypertension Study, Captopril Prevention Project, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial, and Valsartan Antihypertensive Long-Term Use Evaluation. Trials comparing ACEI or ARB against placebo in patients at high risk of cardiovascular events have not showed a consistent result; cardiovascular outcomes were reduced in Heart Outcomes Prevention Evaluation, European Trial on Reduction of Cardiac Events with Perindopril in Stable Coronary Artery Disease, and the Jikei Heart Study, but were not significantly reduced in Perindopril Protection Against Recurrent Stroke Study, Comparison of Arnlodipine vs Enalapril to Limit Occurrences of Thrombosis Trial, Prevention of Events with ACEIs Trial, Telmisartan Randomized Assessment Study in ACE-Intolerant Subjects with Cardiovascular Disease Trial, and Prevention Regimen for Effectively Avoiding Second Strokes Trial. In the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial, combining ACEIs with ARBs in high-risk patients did not reduce cardiovascular or renal outcomes compared with ACEI monotherapy alone. This absence of a reduction in cardiovascular outcome from the ACEI and ARB combination arm is further evidence suggesting that these drugs do not have any special cardiovascular protective effect. This objective review thus shows that the rennin-angiotensin antagonists do not have special cardiovascular protective properties. CONCLUSION: The key to reducing cardiovascular outcome is to appropriately control blood pressure as well as to treat all other coronary risk factors.

Statin alternatives or just placebo: an objective review of omega-3, red yeast rice and garlic in cardiovascular therapeutics.

OBJECTIVE: The aim of this review is to objectively access the trial evidence on the role of omega-3, red yeast rice and garlic in preventing clinical cardiovascular events. Given the large number of clinical trials favoring statin use in cardiovascular disease, it is important to see if evidence is available for these supplements and whether they could replace statin therapy. DATA SOURCE: A PubMed search was conducted using the keywords 'trial, omega-3, red yeast rice, xuezhikang, garlic, cholesterol, cardiovascular, outcomes'; the resulting trials were reviewed together with the references quoted in the papers obtained. STUDY SELECTION: The studies selected are prospective, randomized, placebo-controlled studies with predefined clinical cardiovascular end-points recruiting at least 2000 patients, with a follow-up over 2 years. RESULTS: Modest dose omega-3 fatty acid has been shown in GISSI-P (11 324 patients, follow-up 3.5 years) to produce a reduction in sudden death of 45%, and in cardiac death of 35%, acting probably via an anti-arrhythmic effect. In JELIS (18 645 patients, follow-up 4.6 years), high dose omega-3 given to Japanese patients on a high fish diet and already on statin treatment produced further benefit with a 19% reduction of nonfatal cardiovascular outcomes; fatal cardiac events are not affected. CCSPS (4870 patients, follow-up 4 years), a secondary prevention trial using xuezhikang, a commercial red yeast rice preparation, produced a 46% reduction in nonfatal myocardial infarction and coronary death. There has been no trial to show that garlic reduces clinical cardiovascular outcomes. A rigorous trial with constant assessment of chemicals in the study material in 192 patients found that over a 6-month follow-up, raw garlic and 2 commercial preparations do not significantly affect lipid levels. CONCLUSIONS: Omega-3 in modest doses reduces cardiac deaths, and in high doses reduces nonfatal cardiovascular events. Red yeast rice reduces adverse cardiac events to a similar degree as the statins. It is unlikely that garlic is useful in preventing cardiovascular disease.

Impact of various continuing medical education activities on clinical practice - a survey of Malaysian doctors on its perceived importance.

INTRODUCTION: Medical talks, newsletter circulars, scientific meetings and conferences, and interaction with members of the pharmaceutical industry, have become convenient means of carrying out continuing medical education (CME) for many busy doctors. MATERIALS AND METHODS: To study the perceived importance of these various CME activities, a self-completed posted questionnaire survey was conducted among registered practitioners of a densely populated urban state in Malaysia. RESULTS: Of the 172 respondents [male, 77%; hospital-based, 37%; general practitioner (GP), 55%; private practice, 70%; respondent rate of 19.5%], most preferred local conferences and endorsements by local experts to their foreign counterparts. Meetings or conferences sponsored by the pharmaceutical industry were ranked similarly with those without such links, while the reputation of the pharmaceutical firms was of foremost importance. Among GPs (n = 95) and non-GPs (n = 77), medical society newsletters were rated significantly higher by GPs while overseas conferences were rated higher by non-GPs. CONCLUSION: Our findings provide an important first look at this under-explored area among Malaysian doctors and described a high degree of acceptance for the involvement of the pharmaceutical industry in CME activities.

Seeking the ideal anti-hypertensive agent: a practical review of the hypertension drug trials.

Numerous trials and meta-analyses have been conducted over the last five years to identify an ideal anti-hypertensive drug. These reports, and the JNC 7 and European hypertension guidelines, have generated some controversy and confusion. A review of the comparative anti-hypertensive drug trials shows that the differences between drugs are minor and not consistently demonstrated by different studies. However, much data have now accumulated on the safety and value of diuretics, beta blockers, calcium-channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) in reducing blood pressure and preventing clinical disease. The importance of tight blood pressure control in reducing adverse events has been clearly shown, and clinicians should concentrate on achieving target blood pressure levels, which often requires a combination of anti-hypertensive drugs. The choice of anti-hypertensive drug should be guided by the presence of concomitant clinical disease, as evidence has accumulated on the special efficacy of certain drugs in reducing damage to particular organ systems. In the absence of any associated clinical disease, it is good to initiate anti-hypertensive therapy with diuretics, provided the metabolic parameters are regularly reviewed.