[Anti-ischemic and infarction-reducing effects of angiotensin-converting enzyme inhibitors]. / Antiiskemisk og infarktbegrensende effekt av angiotensinkonverterende enzymhemmere.

BACKGROUND: Angiotensin-converting enzyme is probably involved in the pathogenesis and progression of atherosclerosis, both through an increase in vascular angiotensin II and by an effect on the degradation of bradykinin into inactive fragments. Moreover, angiotensin II has a prothrombotic effect and prevails in increased concentration in the blood of animals subjected to experimentally induced myocardial infarction. MATERIAL AND METHODS: We have evaluated the relevant literature (including animal experiments and human studies) describing the infarct-reducing and anti-ischaemic effects of angiotensin-converting enzyme inhibitors. We also refer to studies in which these drugs have reduced the progression of atherosclerosis. RESULTS: Angiotensin-converting enzyme inhibitors probably have favourable effects in various ways. There are indications that they counteract ischaemia, reduce heart failure and prevent reinfarction. Experimental observations in animals also indicate that angiotensin-converting enzyme inhibitors limit myocardial injury, presumably in part through the effects of bradykinin. This is supported by some few clinical studies, including a Norwegian epidemiological study. Angiotensin-converting enzyme inhibitors reduced the progression of intima-media thickness in the carotid arteries. INTERPRETATION: Angiotensin-converting enzyme inhibitors have favourable biochemical and haemodynamic properties that may explain their beneficial effects in patients with coronary heart failure.

[Smoking and coronary heart disease]. / Røyking og koronar hjertesykdom.

BACKGROUND: Smoking increases the risk of developing coronary heart disease in men and women. MATERIALS AND METHODS: Several epidemiological studies have demonstrated an almost linear relationship between smoking and coronary heart mortality and morbidity, the risk being more than twofold and most pronounced in younger individuals. RESULTS: Smokers are younger than nonsmokers when they suffer their first myocardial infarction, more of them are males, and they experience more frequently posterior infarcts. They are likely to develop right coronary occlusions, the lesions being rather thrombogenic than atherosclerotic. This phenomenon may partly be related to the specific flow pattern in the right coronary artery. Passive smoking is harmful. Quitting smoking in patients and in healthy individuals reduces the risk markedly within a short period of time. INTERPRETATION: Smoking causes vasoconstriction of coronary arteries, and endothelial function as well as fibrinolysis is impaired while platelets are activated. A human ex-vivo experimental model has shown that the thrombus volume was increased twofold in blood from smokers at shear forces that are found in moderately stenosed coronary arteries. In addition, smokers are insulin-resistant and at increased risk of developing diabetes mellitus.

Effects of a high-dose concentrate of n-3 fatty acids or corn oil introduced early after an acute myocardial infarction on serum triacylglycerol and HDL cholesterol.

BACKGROUND: Results of epidemiologic studies and clinical trials indicate that moderate doses of n-3 fatty acids reduce the risk of cardiovascular disease and may improve prognosis. OBJECTIVE: The objective was to evaluate the effect of a high-dose ethylester concentrate of n-3 fatty acids administered early after an acute myocardial infarction (MI) on subsequent cardiac events and serum lipids. DESIGN: Three hundred patients with acute MI were randomly assigned to a daily dose of either 4 g highly concentrated n-3 fatty acids or corn oil, administered in a double-blind manner over 12-24 mo. Median follow-up time was 1.5 y. Clinical follow-up, including the drawing of blood samples, was performed after 6 wk of treatment and later at 0.5-year intervals. RESULTS: Forty-two (28%) patients in the n-3 group and 36 (24%) in the corn oil group experienced at least one cardiac event (cardiac death, resuscitation, recurrent MI, or unstable angina). No significant difference in prognosis was observed between groups for single or combined cardiac events. Total cholesterol concentrations decreased in both groups, with no significant intergroup differences. On average, the monthly increase in HDL cholesterol was 1.11% in the n-3 group and 0.55% in the corn oil group (P = 0.0016). Triacylglycerol concentrations decreased by 1.30%/mo in the n-3 group, whereas they increased by 0.35%/mo in the corn oil group (P < 0.0001). CONCLUSION: No clinical benefit of a high-dose concentrate of n-3 fatty acids compared with corn oil was found despite a favorable effect on serum lipids.

[Are the newer antihypertensive agents better and more effective than diuretics?]. / Er de nyere antihypertensive medikamentene bedre og mer effektive enn diuretika?

BACKGROUND: In recent years, the expenses for medical antihypertensive therapy have increased considerably, the main reason being the switchover to newer and more expensive antihypertensive drugs. RESULTS: Several recent studies which have compared the efficacy of the older, conventional drugs (thiazid diuretics and beta-blockers) with the newer agents (calcium blockers, angiotensin-converting enzyme (ACE) inhibitors), have shown that they are almost equipotent with regard to effects on blood pressure, morbidity and mortality. At lower doses, the metabolic effects of thiazide diuretics are minimal and probably without clinical significance, and the risk of developing diabetes mellitus type 2 does not seem to be increased. INTERPRETATION: The cheaper thiazide diuretics are still valuable drugs in the treatment of hypertension. If more than one agent is necessary to reduce blood pressure to the desired level, they can be combined with other antihypertensive agents.

[Nutrition, dietary supplementation and coronary heart disease]. / Ernaering, kosttilskudd og koronar hjertesykdom.

BACKGROUND: During the last decade, lipid lowering agents, in particular statins, have become increasingly important in the treatment of cardiovascular diseases and dyslipidaemias. This might imply that emphasis on diet and supplementary nutrients do not receive sufficient attention. MATERIAL AND METHODS: On the basis of studies of the literature, the scientific documentation for a possible beneficial effect of the following elements are reviewed: intake of fat, fish and fish oil, alpha-linolenic acid, folic acid, vitamin B6 and vitamin B12, nuts, plant sterols and psyllium. RESULTS: Reduced intake of saturated fat causes improvement in serum lipid values and prevents cardiovascular events. Intake of fish, fish oils and alpha-linolenic acid has positive effects on several clinical end points, often without marked decrease in serum cholesterol. Homocysteine appears to be an independent risk factor for cardiovascular diseases, but a causal relationship remains to be proven. The cofactors folic acid, vitamin B6 and B12 reduce the homocysteine level, but effects of this intervention on hard clinical end points are lacking. There are indications that intake of nuts can prevent coronary events. Plant sterols and psyllium in the diet reduce cholesterol levels. INTERPRETATION: Thus, dietary intervention is important in the prevention and treatment of coronary heart disease. Also when drug treatment is indicated, a focus on diet and nutrient supplementation is highly warranted. Some nutrients may have preventive effect in relation to coronary events, despite their small effect on cholesterol levels.

More non-Q-wave myocardial infarctions but similar infarct sizes in patients with hypertension.

Of 350 consecutive patients without previous symptoms of coronary artery disease, admitted to hospital with an acute myocardial infarction, 109 of them (31%) reported a history of previous hypertension. Hypertensive patients were older than their normotensive counterparts, more of them were females, and thrombolytic treatment was administered to significantly fewer. Blood pressure values at admission to hospital were higher in hypertensive patients; this difference was significant in hypertensive males. Altogether 44 out of 49 female (90%) and 42 out of 60 male hypertensive patients (70%) reported using antihypertensive medication. A previous history of hypertension did not change infarct size as assessed by peak enzyme levels, neither in the bivariate nor in the multivariate analysis. In contrast to this, the adjusted odds ratio for developing a non-Q-wave infarct was 2.51 (p=0.003), i.e. the chance of developing a non-Q-wave infarct in hypertensives was increased by 151%. Thus, in spite of similar infarct size in normotensive and hypertensive patients, a relative smaller proportion of the probably hypertrophied left ventricular wall developed necrosis in the hypertensive population. The propensity towards non-Q-wave infarctions may contribute to the observed less use of fibrinolytic drug treatment in the presently observed patients with hypertension.

Current smokers develop more posterior myocardial infarctions probably due to increased tendency to thrombosis.

This investigation was carried out to determine whether smokers developed smaller infarcts as assessed by peak enzyme levels and also to what extent smoking could modify infarct localization. The study included 753 patients, of whom 351 had no history of previous coronary heart disease (CHD) (angina pectoris and/or myocardial infarction (MI)). The investigation was designed as an exposed (smoking) versus non-exposed (non-smoking) cohort study. Outcome was infarct size, posterior versus non-posterior MI and non-Q-wave versus Q-wave infarcts. In the total cohort of patients, 312 (41%) were smokers, the corresponding number in the restricted cohort of patients without a previous CHD (CHD-0-pts) was 169 (48%). Smokers were younger than non-smokers, and more of them were males. It was found that infarct size was similar in smokers and in non-smokers (crude and adjusted effects). Crude effects showed that smokers developed significantly more posterior infarcts than non-smokers; odds ratio (OR) for developing a posterior MI was 1.95 (2p < 0.001) (all patients) and 2.34 (2P < 0.001) (CHD-0-pts), respectively. After adjusting for confounders (logistic regression model), OR in the two groups was 1.24 (2p = 0.256) and 1.95 (2p = 0.01), respectively. The study shows that current smokers were younger, and indicates that in those without a previous CHD, significantly more of them developed a posterior MI.

Infarct size is reduced and the frequency of non-Q-wave myocardial infarctions is increased in patients using aspirin at the onset of symptoms.

In an observational study we wanted to investigate whether ongoing use of aspirin in a cohort of 753 patients with acute myocardial infarction was able to (1) reduce infarct size as assessed by peak creatine kinase and lactate dehydrogenase, (2) increase the number of non-Q-wave myocardial infarctions, and (3) to what extent thrombolytic treatment at admission could modify these outcomes. We used an exposed (aspirin+)/nonexposed (aspirin-) cohort design, adjusting for the effects of confounders (age, previous coronary heart disease, current smoking, and the prior use of beta-blockers and long-acting nitrates) as well as for the modifying effect of thrombolytic treatment. Crude and adjusted effects showed that aspirin reduced infarct size only in patients not receiving thrombolytic treatment at admission to hospital (n = 411 patients). In analyzing the occurrence of non-Q-wave versus Q-wave myocardial infarctions, the outcome was dichotomized. Crude odds ratio (OR) for developing a non-Q-wave myocardial infarction in aspirin users was 2. 63 (2p < 0.001), in the restricted cohort of patients receiving thrombolytic treatment, OR was 3.46 (2p = 0.002), whereas in those not receiving such treatment, OR was 1.81 (2p = 0.007). Adjusting for the effects of confounders, retained aspirin was an independent predictor of non-Q-wave myocardial infarctions, an effect that was probably increased (from 51 to 128%) in those who received thrombolytic treatment. Thus, aspirin seems to produce a shift to less severe manifestations of myocardial infarction, an effect that was increased in patients given thrombolytic treatment at admission to hospital.

[The effect of reduced cholesterol on coronary arteries]. / Virkningen av kolesterolsenkning på koronararterier.

High levels of cholesterol increase the influx of calcium ions into vascular smooth muscle cells, thereby increasing vascular tone and resistance. Simultaneously, endothelium-dependent (NO-mediated) vasodilatation is inhibited in the arteries. Brief reductions in cholesterol induced by dietary intervention or with lipid lowering therapy normalize endothelial dysfunction, and myocardial perfusion will increase well before any beneficial effects on atherosclerosis are detected. These phenomena may explain, at least in part, that in spite of even small differences in angiographic findings between patients who have undergone treatment and those who have not, lowering lipids will cause major reductions in cardiovascular events. Lowering the levels of cholesterol will alter the content and composition of atherosclerotic plaques, thereby making them more stable. The result is probably a substantial reduction in the frequency of plaque rupture, and if rupture should occur, the thrombotic mechanisms will probably be weaker. Consequently, the risk of a thrombotic occlusion of a coronary vessel will be reduced.

[Fish, fish oils, arrhythmias and sudden death]. / Fisk, fiskeoljer, arytmier og plutselig død.

Cardiovascular morbidity and mortality is relatively low in individuals with a high consumption of fish oils containing omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid). This has been mainly attributed to the anti atherogenic and anti thrombotic effects of these oils. However, recent evidence suggests that fish and fish oils may also prevent malignant ventricular arrhythmias and sudden cardiac death. Several animal experiments have shown that fish oils can reduce the incidence of ischaemia induced ventricular tachycardia and fibrillation. Observational studies in humans have shown that there is a connection between the intake of omega-3 fatty acids and a lower risk of sudden cardiac death. Some trials suggest that fish oils can prevent ventricular arrhythmias in humans. It is possible that the effect of fish oils on arrhythmias is independent of their anti atherogenic and anti thrombotic activities. There is also some evidence that these oils affect ion fluxes in cardiomyocytes.

Acute myocardial infarction mortality related to use of calcium antagonists before admission to hospital.

We investigated whether prior use of calcium antagonists in 80 (16.8%) out of 477 patients (64% males) admitted with acute myocardial infarction (MI) had any impact on in-hospital mortality. Patients using calcium antagonists were slightly older (74 years vs. 72 years, 2P = 0.039) than those not taking them and fewer were male patients. Previous MI, diabetes mellitus, and prior use of aspirin, beta-blockers, and long-acting nitrates were more frequent in patients on calcium antagonists. In contrast, fewer patients on calcium antagonists prior to symptoms received thrombolytic treatment (21.3% vs. 34.8%, 2P = 0.018). The study had an observational exposed/nonexposed design, and we looked for both crude and adjusted effects. Of the 83 patients (17.4%) who died during hospitalization, 18 patients were in the calcium antagonist group (22.5%). The odds ratio (OR) for these patients to die in the hospital was 1.48 and the 95% confidence interval (CI) 0.78-2.78; 2P = 0.19. When adjusting for confounders (gender, age, smoking habit, previous MI, and diabetes mellitus, as well as prior use of aspirin, beta-blockers, long-acting nitrates, and thrombolytic treatment at entry) OR was 1.08 and 95% CI 0.57-2.05; 2P = 0.85. Thus, we found no excess in-hospital mortality in patients with acute MI using calcium antagonists prior to the onset of symptoms.

Use of fish oils appears to reduce infarct size as estimated from peak creatine kinase and lactate dehydrogenase activities.

In 753 patients with acute myocardial infarction, use of fish oils (FO, n = 242) before onset of infarction seemed to reduce infarct size as estimated from peak creatine kinase (CKmax) and lactate dehydrogenase (LDmax) activities. The study had an observational exposed/nonexposed design, and both crude and adjusted effects were looked for. CRUDE EFFECTS: In the restricted cohort of patients not receiving thrombolytic treatment (n = 411), FO reduced CKmax from 879 to 759 U/l (2 p = 0.030) and LDmax from 870 to 768 U/l (2 p = 0.011), respectively. More of these patients in the lowest enzyme quartiles used FO, p for linear trend was for CKmax 0.008 and for LDmax 0.06, respectively. ADJUSTED EFFECTS: In patients not receiving thrombolytic treatment, FO reduced CKmax (2 p = 0.007) and LDmax (2 p = 0.005), but in patients receiving such treatment, CKmax and LDmax values increased, 2 p being 0.036 and 0.097, respectively. In patients not receiving thrombolysis, FO increased the incidence of small infarcts (the 25% quartile), odds ratio for CKmax was 1.82 (2 p = 0.018) and for LDmax 1.66 (2 p = 0.048), respectively. The results indicate that FO may reduce infarct size and the incidence of large infarcts. In addition, FO seems to enhance the effect of thrombolysis.

Eating fish may reduce infarct size and the occurrence of Q wave infarcts.

OBJECTIVE: The present investigation was carried out to see whether intake of fish could influence infarct size as assessed by peak enzyme levels (CKmax and LDmax) as well as the occurrence of Q wave infarcts. DESIGN: The investigation was a prospectively planned cohort study. SETTING: The investigation was carried out at Ullevål University Hospital, Department of Cardiology and Department of Pharmacotherapeutics, University of Oslo, Oslo, and in four other Hospitals in Oslo and Lillehammer. SUBJECTS: Seven hundred and forty-five patients (median age 70 y, 64% males) admitted with proven acute myocardial infarction. RESULTS: Crude effects showed that the regression lines between the number of fish meals/week (FM/week) and CKmax in all patients and in the restricted cohorts of patients receiving/not receiving thrombolytic treatment were: y = 2086-157.x(2P = 0.004); y = 2807-156.x (2P = 0.110) and y = 1260-54.x (2P = 0.230); the corresponding results regarding LDmax were: y = 1329-76.x (2P = 0.009); y = 1556-73.x (2P = 0.120) and y = 1047-39 x (2P = 0.230). Odds ratio (OR) for developing Q wave infarcts in patients consuming > 1.0 FM/week was 0.52, 95% confidence interval (CI) 0.34-0.79; 2P = 0.001. For the adjusted effects, the coefficients of FM/week for log (peak enzyme levels) in all three groups of patients (all patients, and the restricted cohorts of patients receiving/not receiving thrombolytic treatment) were negative with 2P values of 0.014, 0.033 and 0.165 (CKmax), and 0.006, 0.033 and 0.158 (LDmax). OR for developing Q wave infarcts in patients consuming > 1.0 FM/week was 0.59, 95% CI 0.38-0.92; 2P = 0.022. CONCLUSIONS: The results indicate that consuming fish may reduce infarct size as assessed by CKmax and LDmax as well as the occurrence of Q wave infarcts.

Infarct size as estimated from peak creatine kinase and lactate dehydrogenase is probably reduced in patients using calcium antagonists at the onset of symptoms.

In animal models, calcium antagonists (Ca-A) administered before ischemia and reperfusion reduced myocardial necrosis, attenuated postischemic contractile dysfunction, and reduced tissue calcium. In 753 patients with acute myocardial infarction (AMI), we examined if use of Ca-A at the onset of symptoms (n = 127 patients) reduced infarct size as estimated from peak creatine kinase (CKmax) and lactate dehydrogenase (LDmax) activities. The study had an observational exposed/nonexposed design, and both crude and adjusted effects were investigated. Crude effects: In the restricted cohort of patients not receiving thrombolytic treatment (thr- pts; n = 411 patients), CKmax and LDmax were lower in Ca-A+ patients than in Ca-A- patients, being 643 versus 887 U/l (2 p = 0.004) and 708 versus 867 U/l (2 p = 0.005), respectively. When using log (CKmax) and log (LKmax) as outcomes, the same results were found (2 p = 0.002). More of the restricted cohort of the pts used Ca-A in the lower quartiles of CKmax and LDmax (p for linear trend = 0.005 and 0.004 for CKmax and LDmax, respectively). Adjusted effects: Thrombolysis was an effect modifier of the association between Ca-A and peak enzyme levels. In thr-pts, the coefficients of Ca-A were negative and borderline significant for log (CKmax; 2 p = 0.088) and negative and highly significant for log (LDmax; 2 p = 0.010) when adjusting for confounders. The present observational study indicates that the use of a Ca-A at the onset of AMI reduces infarct size, as estimated from CKmax and LDmax activities.

[Acetylsalicylic acid in the treatment of cardiovascular and cerebrovascular diseases]. / Acetylsalisylsyre i behandlingen av kardiovaskulaere og cerebrovaskulaere sykdommer.

This year acetylsalicylic acid (aspirin) celebrates its 100-year anniversary. While the drug was previously used mainly as an antipyretic and a pain-killer, aspirin has, during the last 10-15 years, become one of the most important agents in the treatment of cardiovascular and cerebrovascular diseases. In addition to being one of our oldest drugs, aspirin is one of the most interesting and widely used remedies. The antithrombotic property of aspirin is mainly related to its irreversible inhibition of the production of platelet-derived thromboxane A2, which possesses aggregatory and vasoconstrictive properties. Aspirin reduces the risk in patients with overt cardiovascular and cerebrovascular diseases, i.e. chronic stable and unstable angina pectoris. It also reduces the risk in the acute phase of and following a myocardial infarction and after a transient ischemic attack or stroke. The use of the drug is controversial in primary cardiovascular prevention. Overall mortality is not reduced, and side-effects, such as increased bleeding tendency, may be serious. This side-effect is dose-dependent, and smaller doses (75-160 mg) which have the same effect as higher doses should be preferred.