Cholesterol fairy home to roost

Bandolier 86 we asked why it was that we have to take our statins (usually) in the evening. We thought it might have been a simple pharmacokinetic explanation (short half-lives meaning that statins were more effective in the evening). Some of you wrote with the half-lives (many thanks), but pointed out that with time this should not matter much, even if cholesterol synthesis was higher at night.

Hard evidence was hard to find. What was required was a large study demonstrating that normal doses of evening statin produced convincingly lower cholesterol levels than normal doses of morning statin. A number of readers sent suggestions about papers we should read, and some of these we had read ourselves.

But even so, no convincing evidence. As best we can understand it, the evidence, such as it is, comes from a single study in Japan done 10 years ago [1]. It is a good study, but it doesn't answer the question.

Meta-Meta-Analysis

To add to the 'King Kong versus Godzilla' arguments about whether a single large randomised trial is better than a meta-analysis of smaller trials we now have to add problems of discrepancies of meta-analyses themselves. The study of the value of cholesterol lowering and the effects on coronary heart disease [1] is the first Bandolier has found which looks at the results of different meta-analyses and tries to prise out nuggets of philosophical gold.

Is cholesterol lowering beneficial?

Twenty-three separate meta-analyses were found. Outcomes examined were those of total mortality, cardiovascular mortality and nonfatal cardiovascular disease. As the Table shows, the results of the analyses overwhelmingly supported cholesterol lowering for reduction in nonfatal cardiovascular disease and cardiovascular mortality, but not total mortality.

Consumption of different types of alcohol and mortality

We know that a moderate amount of alcohol consumption is beneficial for health. What we don't know for certain is whether the type of alcohol makes a difference. This paper examines the effect of wine, beer and spirits on death from all causes, coronary heart disease and cancer.

Sudden cardiac death

It becomes obvious when one begins to write about risk, as Bandolier has been doing in recent issues, that some sort of background is needed. Risk examines mainly serious consequences, most often death. While Keynes' dictum about us all being dead in the long run is all very well, it is the short run that we worry about most

Lifetime risk of coronary heart disease

Coronary heart disease is the leading cause of death worldwide, yet there were no estimates of the lifetime risk of coronary heart disease until this paper was published.

Participants were almost exclusively white. Between 1% and 10% of participants suffered from diabetes, between 19% and 49% were current smokers, between 15% and 69% suffered from hypertension and cholesterol levels ranged from 5.0 to 6.3 mmol/L. (The higher incidence of hypertension and higher cholesterol levels were among the older adults.)

The risk of developing coronary heart disease before 40 years old was low, 1.2% in men and 0.2% in women.

At 40 years old, the lifetime risk of coronary heart disease was 48.6% for men and 31.7% for women. Table 1 shows the risks for men and women at the next three decades

Is uric acid related to heart disease?

There have been suggestions that elevated uric acid levels are associated with increased heart disease, and death from heart disease. The problem is that elevated uric acid levels are found when people are overweight, and when they have other risk factors also associated with heart disease. Teasing out whether uric acid, per se, is an independent risk factor will be difficult. There are two good epidemiological studies that reach opposite conclusions

Can personality predict risk of coronary heart disease?

Many potential psychosocial risk factors for coronary heart disease have been identified including stress, Type A behaviour pattern, hostility and physiological reactivity to stress. This meta-analysis investigates the associations between coronary heart disease and Type A personality and hostility. Type A behaviour pattern is characterised by an excessive competitive drive, impatience and anger/hostility. While initial research investigated the overall Type A behaviour pattern, more recent studies have focused on its components, particularly hostility.

asthma, COPD, respiratory problems

In these pages are collected the stories from Bandolier relating to allergy, asthma and respiratory problems, including COPD. In due course these will be supplemented by additional material, as resources become available through sponsorship or other means.

Bandolier Knowledge

In this section Bandolier collects good quality evidence under a variety of different headings. We search for systematic reviews of treatments, of evidence about diagnosis, epidemiology or health economics, and abstract it. It is time consuming, and Bandolier has been able to do it only through sponsorship, which is a limiting factor. Sponsorship is acknowledged at the top of each topic heading. The fundamental criterion is that sponsors have no say or control whatsoever. Users who know of no-strings funding to maintain our independent status, please let us know.

Incidental TOE finding - Carpentier mitral annuloplasty ring dehiscence during heart transplantation

A 57-year-old male with heart failure from dilated cardiomyopathy was scheduled to undergo heart transplant. Other cardiac comorbidities included chronic atrial fibrillation, severe pulmonary hypertension, severe mitral regurgitation with history of mitral valve repair and implantation of 29-mm annuloplasty ring earlier. The patient also had an automated implantable cardioverter-defibrillator for ventricular tachycardia therapy and termination. The last surgical procedure prior to the heart transplant was laparoscopic cholecystectomy at an outside hospital complicated by intraoperative cardiac arrest, necessitating prolonged cardiopulmonary resuscitation. The trans-thoracic echocardiogram postresuscitation showed severe and worse mitral regurgitation with no mention of mitral ring pathology.

Following the induction of anaesthesia for heart transplant, transoesophageal echocardiographic (TOE) examination revealed severe eccentric mitral regurgitation and the dramatic appearance of a total mitral ring dehiscence with the new appearance of severe dilatation of the mitral annulus. The ring appeared to be freely floating in the left atrium . Following the commencement of cardiopulmonary bypass and recipient cardiectomy, the gross inspection of the transected heart revealed a 29-mm Carpentier-Edwards annuloplasty ring dehisced along the valve circumference . One of the possible etiologies proposed was traumatic dehiscence following protracted chest compressions when the patient arrested intraoperatively during the laparoscopic cholecystectomy. Also likely was primary failure of the ring annuloplasty. This patient went on to have an uneventful heart transplant. The purpose of this brief report is to illustrate the superiority of TOE over transthoracic echocardiography, particularly in the evaluation of mitral valve disease. In this patient, the dehisced annuloplasty ring may have worsened the mitral regurgitation. In this situation, it did not influence the outcomes since the heart was transplanted. The author makes the recommendation that all patients with prosthetic valves and annuloplasty rings should have thorough TOE evaluation following chest compression during cardiopulmonary resuscitation

Systematic review

The review sought studies with patients diagnosed with previous heart attack, or stable or unstable angina and who were smoking at baseline with smoking status well defined. Prospective cohort studies had to include current smokers at baseline, with smoking status measured to find who had quit smoking, in which the follow up was at least two years and with all cause mortality as an outcome measure.

The search strategy was extensive, examining nine electronic databases, and studies were not restricted by language.

Results

There were 20 included studies with 12,600 patients, mostly using data collected in the 1960s and 1970s. Most cases were men (80%), and average cessation rate was 45%. Follow up ranged from two to 26 years, though most studies reported follow up of three to seven years, with a mean of five years.

Most studies involved follow up hospital case series, and reporting of smoking status was usually at some follow up appointment, though it was not validated, for example by biochemical measurement, in most studies. Most studies had a clear definition of the cardiac event. Loss to follow up was usually small. Size varied from under 100 to over 4,000 patients.

There were fewer deaths in quitters (18%) than in people who continued to smoke (27%), and the degree of reduction was consistent across all death rates reported (Figure 1). Results were broadly similar in all studies, and in six higher quality studies with about two-thirds of all patients (Table 1). Higher quality here was defined by a sample size of 500 smokers at baseline, with fewer than 15% dropouts, and with adequate or good control of confounding.

Smoking with CHD

All of us deal with risk every day. If you drive on the roads in the UK, you accept a (roughly) 1 in 18,000 chance of dying in a road accident in one year. Given the volume of traffic on our roads, that is a risk most of us are willing to accept. But it is not an unthinking acceptance, because many of us try to minimise the risk by driving carefully, and especially by buying safer cars with air bags and crumple zones. Indeed, with cars having a greater longevity than ever, buying a new car may have more to do with safety than reliability, unless you live next door to someone called Jones.

Yet we shrug off much greater risks. Otherwise why would so many of us smoke? A defining moment for many smokers can be surviving a heart attack, when the folly of our behaviour strikes home, and smoking is given up. Others take the more fatalistic view that the damage is already done, or they need a little pleasure in life. A new systematic review [1] tells us the fatalistic view just ain't so, and that smokers with coronary heart disease have an extra 1 in 10 chance of dying over five years because of their smoking.