Guidelines and Expert Consensus documents aim to present management and recommendations based on all of the relevant evidence on a particular subject in order to help physicians to select the best possible management strategies for the individual patient, suffering from a specific condition, taking into account not only the impact on outcome, but also the risk benefit ratio of a particular diagnostic or therapeutic procedure. The ESC recommendations for guidelines production can be found on the ESC website†.

In brief, the ESC appoints experts in the field to carry out a comprehensive and critical evaluation of the use of diagnostic and therapeutic procedures and to assess the risk–benefit ratio of the therapies recommended for management and/or prevention of a given condition. The strength of evidence for or against particular procedures or treatments is weighed according to predefined scales for grading recommendations and levels of evidence, as outlined below. Once the document has been finalized and approved by all the experts involved in the Task Force, it is submitted to outside specialists for review. If necessary, the document is revised once more to be finally approved by the Committee for Practice Guidelines and selected members of the Board of the ESC.

The ESC Committee for Practice Guidelines ( CPG ) supervises and coordinates the preparation of new Guidelines and Expert Consensus Documents produced by Task Forces, expert groups, or consensus panels. The chosen experts in these writing panels are asked to provide disclosure statements of all relationships they may have, which might be perceived as real or potential conflicts of interest. These disclosure forms are kept on file at the European Heart House, headquarters of the ESC. The Committee is also responsible for the endorsement of these Guidelines and Expert Consensus Documents or statements.

 
| Classes of recommendations |
|:-------------------------- | ------------------------------------------------------------------------------------------------------------------------ |
| Class I | Evidence and/or general agreement that a given diagnostic procedure/treatment is beneficial, useful, and effective |
| Class II | Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment or procedure |
|  Class IIa | Weight of evidence/opinion is in favour of usefulness/efficacy |
|  Class IIb | Usefulness/efficacy is less well established by evidence/opinion |
| Class III | Evidence or general agreement that the treatment or procedure is not useful/effective and, in some cases, may be harmful |

Diabetes and cardiovascular diseases (CVD) often appear …

/pdf/guidelines-on-diabetes-pre-diabetes-and-cardiovascular-4j63bs7fb2.pdf

Guidelines on diabetes, pre-diabetes, and cardiovascular diseases: executive summary. The Task Force on Diabetes and Cardiovascular Diseases of the European Society of Cardiology (ESC) and of the European Association for the Study of Diabetes (EASD).

https://ir.ymlib.yonsei.ac.kr/bitstream/22282913/165063/1/T999900135.pdf

Body-mass index and all-cause mortality: individual-participant-data meta-analysis of 239 prospective studies in four continents

Prevention of coronary heart disease in clinical practice: recommendations of the Second Joint Task Force of European and other Societies on Coronary Prevention.

Objective : To estimate by how much and how quickly a given reduction in serum cholesterol concentration will reduce the risk of ischaemic heart disease.

Design : Data on the incidence of ischaemic heart disease and serum cholesterol concentration were analysed from 10 prospective (cohort) studies, three international studies in different communities, and 28 randomised controlled trials (with mortality data analysed according to allocated treatment to ensure the avoidance of bias). Main outcome measure - Decrease in incidence of ischaemic heart disease or mortality for a 0.6 mmol/l (about 10%) decrease in serum cholesterol concentration.

Results : For men results from the cohort studies showed that a decrease of serum cholesterol concentration of 0.6 mmol/l (about 10%) was associated with a decrease in incidence of ischaemic heart disease of 54% at age 40 years, 39% at age 50, 27% at 60, 20% at 70, and 19% at 80. The combined estimate from the three international studies (for ages 55-64 years) was 38% (95% confidence interval 33% to 42%), somewhat greater than the cohort study estimate of 27%. The reductions in incidence of ischaemic heart disease in the randomised trials (for ages 55-64 years) were 7% (0 to 14%) in the first two years, 22% (15% to 28%) from 2.1-5 years, and 25% (15% to 35%) after five years, the last estimate being lose to the estimate of 27% for the long term reduction from the cohort studies. The data for women are limited but indicate a similar effect. Conclusions - The results from the cohort studies, international comparisons, and clinical trials are remarkably consistent. The cohort studies, based on half a million men and 18 000 ischaemic heart disease events, estimate that a long term reduction in serum cholesterol concentration of 0.6 mmol/l (10%), which can be achieved by moderate dietary change,lowers the risk of ischaemic heart disease by 50% at age 40, falling to 20% at age 70. The randomised trials, based on 45 000 men and 4000 ischaemic heart disease events show that the full effect of the reduction in risk is achieved by five years.

/pdf/by-how-much-and-how-quickly-does-reduction-in-serum-2jd350pf3l.pdf

By how much and how quickly does reduction in serum cholesterol concentration lower risk of ischaemic heart disease

ContextEstablishing relative benefit or harm from specific antihypertensive
agents is limited by the complex array of studies that compare treatments.
Network meta-analysis combines direct and indirect evidence to better define
risk or benefit.ObjectiveTo summarize the available clinical trial evidence concerning the safety
and efficacy of various antihypertensive therapies used as first-line agents
and evaluated in terms of major cardiovascular disease end points and all-cause
mortality.Data Sources and Study SelectionWe used previous meta-analyses, MEDLINE searches, and journal reviews
from January 1995 through December 2002. We identified long-term randomized
controlled trials that assessed major cardiovascular disease end points as
an outcome. Eligible studies included both those with placebo-treated or untreated
controls and those with actively treated controls.Data ExtractionNetwork meta-analysis was used to combine direct within-trial between-drug
comparisons with indirect evidence from the other trials. The indirect comparisons,
which preserve the within-trial randomized findings, were constructed from
trials that had one treatment in common.Data SynthesisData were combined from 42 clinical trials that included 192 478
patients randomized to 7 major treatment strategies, including placebo. For
all outcomes, low-dose diuretics were superior to placebo: coronary heart
disease (CHD; RR, 0.79; 95% confidence interval [CI], 0.69-0.92); congestive
heart failure (CHF; RR, 0.51; 95% CI, 0.42-0.62); stroke (RR, 0.71; 0.63-0.81);
cardiovascular disease events (RR, 0.76; 95% CI, 0.69-0.83); cardiovascular
disease mortality (RR, 0.81; 95% CI, 0.73-0.92); and total mortality (RR,
0.90; 95% CI, 0.84-0.96). None of the first-line treatment strategies–β-blockers,
angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers (CCBs), α-blockers,
and angiotensin receptor blockers–was significantly better than low-dose
diuretics for any outcome. Compared with CCBs, low-dose diuretics were associated
with reduced risks of cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00)
and CHF (RR, 0.74; 95% CI, 0.67-0.81). Compared with ACE inhibitors, low-dose
diuretics were associated with reduced risks of CHF (RR, 0.88; 95% CI, 0.80-0.96),
cardiovascular disease events (RR, 0.94; 95% CI, 0.89-1.00), and stroke (RR,
0.86; 0.77-0.97). Compared with β-blockers, low-dose diuretics were associated
with a reduced risk of cardiovascular disease events (RR, 0.89; 95% CI, 0.80-0.98).
Compared with α-blockers, low-dose diuretics were associated with reduced
risks of CHF (RR, 0.51; 95% CI, 0.43-0.60) and cardiovascular disease events
(RR, 0.84; 95% CI, 0.75-0.93). Blood pressure changes were similar between
comparison treatments.ConclusionsLow-dose diuretics are the most effective first-line treatment for preventing
the occurrence of cardiovascular disease morbidity and mortality. Clinical
practice and treatment guidelines should reflect this evidence, and future
trials should use low-dose diuretics as the standard for clinically useful
comparisons.

https://jamanetwork.com/journals/jama/articlepdf/196576/jma20045.pdf

Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis

During a follow-up of five to seven years 33 out of 1222 middle-aged men initially free of coronary heart disease sustained fatal or non-fatal myocardial infarction or died suddenly. The fatty-acid composition of serum triglycerides, phospholipids, and cholesterol esters had been measured at the start of the surveillance in these men and in a control group of 64 men matched for age, serum cholesterol and triglyceride concentrations, blood pressure, obesity, smoking, and one-hour glucose tolerance. Palmitic and stearic acids of phospholipids were significantly higher and linoleic and most polyunsaturated fatty acids, including arachidonic acid and eicosapentaenoic acid, of phospholipids were lower in the subjects who sustained coronary events compared with the controls. Linoleic acid tended to correlate negatively with blood pressure while other polyunsaturated fatty acids, especially eicosapentaenoic acid, exhibited a negative correlation with blood pressure and relative body weight in the controls but not in the subjects who sustained coronary events. These findings suggest that the fatty-acid pattern of serum phospholipids is an independent risk factor for coronary heart disease.

https://www.bmj.com/content/bmj/285/6347/993.full.pdf

Fatty-acid composition of serum lipids predicts myocardial infarction.

Objective. —To investigate the long-term effects of multifactorial primary prevention of cardiovascular diseases (CVD). Design. —The 5-year randomized, controlled trial was performed between 1974 and 1980. The subjects and their risk factors were reevaluated in 1985. Posttrial mortality follow-up was continued up to December 31, 1989. Setting. —Institute of Occupational Health, Helsinki, Finland, and Second Department of Medicine, University of Helsinki. Participants. —In all, 3490 business executives born during 1919 through 1934 participated in health checkups in the late 1960s. In 1974, 1222 of these men who were clinically healthy, but with CVD risk factors, were entered into the primary prevention trial; 612 were randomized to an intervention and 610 to a control group. Interventions. —During the 5-year trial, the subjects of the intervention group visited the investigators every fourth month. They were treated with intensive dietetic-hygienic measures and frequently with hypolipidemic (mainly clofibrate and/or probucol) and antihypertensive (mainly β-blockers and/or diuretics) drugs. The control group was not treated by the investigators. Main Outcome Measures. —Total mortality, cardiac mortality, mortality due to other causes. Results. —Total coronary heart disease risk was reduced by 46% in the intervention group as compared with the control group at end-trial. During 5 posttrial years, the risk factor and medication differences were largely leveled off between the groups. Between 1974 and 1989 the total number of deaths was 67 in the intervention group and 46 in the control group (relative risk [RR], 1.45; 95% confidence interval [Cl], 1.01 to 2.08; P =.048); there were 34 and 14 cardiac deaths (RR, 2.42; 95% Cl, 1.31 to 4.46; P=.001), two and four deaths due to other CVD (not significant), 13 and 21 deaths due to cancer (RR, 0.62; 95% Cl, 0.31 to 1.22; P =.15), and 13 and one deaths due to violence (RR, 13.0; 95% Cl, 1.70 to 98.7; P =.002), respectively. Multiple logistic regression analysis of treatments in the intervention group did not explain the 15-year excess cardiac mortality. Conclusion. —These unexpected results may not question multifactorial prevention as such but do support the need for research on the selection and interaction(s) of methods used in the primary prevention of cardiovascular diseases. ( JAMA . 1991;266:1225-1229)

Long-term Mortality After 5-Year Multifactorial Primary Prevention of Cardiovascular Diseases in Middle-aged Men

In a randomized five-year multifactorial primary prevention trial of vascular diseases, hyperlipidemias, hypertension, smoking, obesity, and abnormal glucose tolerance of the high-risk test group (n=612 men) were treated with dietetic-hygienic measures and hypolipidemic (mainly probucol and clofibrate) and antihypertensive (mainly diuretics and β-blockers) agents. A matched high-risk control group (n=610) and a low-risk control group (n=593) were not treated. The program markedly improved the risk factor status, yet the five-year coronary incidence tended to be higher in the intervention group than in the control group (3.1% vs 1.5%), while the stroke incidence was significantly reduced (1.3% vs 0%). The coronary events tended to be accumulated in subgroups treated with β-blocking agents or clofibrate, but there were few in those receiving probucol or diuretics. Thus, the intervention program significantly reduced development of stroke, but the occurrence of cardiac events was not prevented. Possible adverse drug effects offsetting the probable benefit of improved risk profile are not excluded. (JAMA1985;254:2097-2102)

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=JAMA&articleId=401078&pdfFileName=jama_254_15_027.pdf

Multifactorial primary prevention of cardiovascular diseases in middle-aged men. Risk factor changes, incidence, and mortality.

A longitudinal case-control study of 33 patients with one or more risk factors for coronary heart disease and 64 controls showed that the serum selenium concentration (range 0.63-1.33 mumol/l (50-105 micrograms/l] was not associated with development of clinical manifestations of coronary heart disease during a follow up of five to seven years. The content of polyunsaturated fatty acids, especially eicosapentaenoic acid, in serum cholesterol esters and phospholipids was positively correlated with selenium concentration. As a low content of polyunsaturated fatty acids in serum lipids was an independent risk factor for coronary heart disease in these subjects it may be hypothesised that the high coronary risk in subjects with a very low serum selenium concentration (less than 0.57 mumol/l (less than 45 micrograms/l] might be due not to selenium deficiency but to the coexisting low concentrations of polyunsaturated fatty acids in serum.

Serum selenium concentration related to myocardial infarction and fatty acid content of serum lipids.

OBJECTIVE--to investigate the role of glucose tolerance in the development of hypertension. DESIGN--Retrospective analysis of the results of a health check up in a group of clinically healthy middle aged men in the late 1960s (median year 1968). The subjects were invited to enter into a primary prevention trial for cardiovascular disease in 1974, when they underwent clinical examination for risk factors. The trial was completed in 1979, when the men were re-examined. Follow up was in 1986. SETTING--Institute of Occupational Health, Helsinki, Finland and second department of medicine, University of Helsinki. SUBJECTS--In all, 3490 men born during 1919-34 participated in a health check up in the late 1960s. In 1974, 1815 of these men who were clinically healthy were entered into a primary prevention trial for cardiovascular disease. On clinical examination 1222 of the men were considered at high risk of cardiovascular disease. Of these, 612 received an intervention and were excluded from the study. A total of 593 men were without risk factors. The study comprised all of the men who did not have an intervention (n = 1203). In 1979, 1120 men were re-examined, and in 1986 945 men attended follow up. There were two groups for analysis: one comprising all subjects and the other comprising only men who were normotensive in 1968 and for whom complete information was available. INTERVENTIONS--By 1979, 103 men were taking antihypertensive drugs, and by 1986, 131 were taking antihypertensive drugs and 12 were taking drugs for hyperglycaemia. MAIN OUTCOME MEASURES--Blood glucose concentration one hour after a glucose load, blood pressure, and body weight were measured in 1968, 1974, and 1979. In 1986 blood pressure and body weight were recorded. RESULTS--Men who were hypertensive in 1986 had significantly higher blood pressures (p less than 0.0001) and (after adjustment for body mass index and alcohol intake) significantly higher blood glucose concentrations one hour after a glucose load at all examinations than those who were normotensive in 1986. Regression analysis showed that the higher the blood glucose concentration after a glucose load in 1968 the higher the blood pressure during the following years. Those men between the second and third tertiles of blood glucose concentration in 1968 had a significantly higher risk of developing hypertension (odds ratio 1.71, 95% confidence interval 1.05 to 2.77) compared with those below the first tertile. CONCLUSION--In this study men who developed hypertension tended to have shown an increased intolerance to glucose up to 18 years before the clinical manifestation of their disorder. Blood glucose concentration one hour after a glucose load was an independent predictor of future hypertension.

Vesa Naukkarinen

Papers

Fatty-acid composition of serum lipids predicts myocardial infarction.

Long-term Mortality After 5-Year Multifactorial Primary Prevention of Cardiovascular Diseases in Middle-aged Men

Multifactorial primary prevention of cardiovascular diseases in middle-aged men. Risk factor changes, incidence, and mortality.

Serum selenium concentration related to myocardial infarction and fatty acid content of serum lipids.

Glucose tolerance and blood pressure: long term follow up in middle aged men.