A comprehensive review on the role of cholesterol in health and a critique of the use of statins has recently been published by a team of Japanese researchers (1). This pulls together information from a range of different sources. The focus is on all-cause mortality because fundamentally that is the key parameter most people understand and wish to control. Determination of individual diseases are subject to bias and lack of objectivity, which does not apply to death. The relationship between all-cause mortality and the cholesterol in the blood has now been investigated repeatedly in many different countries and the results which are incredibly consistent may come as a surprise to many people. In this blog I will refer to a selection of what is available.
Japan
In the Ibaraki Prefecture Health Study, 91,219 men and women aged 40-79 years without any history of stroke or coronary heart disease (CHD) were followed for just over 10 years. It was found that the all-cause mortality was inversely correlated with the level of LDL cholesterol. In other words the higher the LDL cholesterol the greater the life expectancy, which of course is in direct conflict with the conventional wisdom.
In the Isehara Study, data was collected from those who had an annual check-up. The final database contained information on 8,340 men (aged 64±10 years) and 13,591 women (61±12 years). Again it was found that the level of LDL cholesterol was inversely related to the all-cause mortality rate. Interestingly it was reported that, the mortality rates due to cancer in men and to respiratory disease without cancer (mostly pneumonia) in men and women were lowest in those groups with the highest values.
The Jichi Medical School Cohort Study is one of the most recent, large epidemiological studies conducted in Japan in which 12,234 healthy adults from rural communities were followed for almost 12 years. Once again, the highest death rates from all causes was in those with the lowest TC values. In this investigation even the exclusion of deaths within the first 5 years did not alter the relationship between low TC levels and the high mortality. The exclusion of deaths caused by liver disease also made no difference to this conclusion. However in this study the relationship between the death rates and TC levels in men was U-shaped so there was some increase at the higher values. But in women it was clear that as the higher the TC, the lower the death rate.
Norway
The results of the Jichi Study are very similar to those obtained in the HUNT Study conducted in Norway, in which 52,087 men and women aged 20-74 years were followed over a 10-year period (2). TC levels were measured and details of any deaths which occurred were recorded. The results are shown in Table 1.
For both men and women, the highest all-cause mortality was in those with the TC levels below 5.0 mmol/L.
In men, there was no increase in the all-cause mortality with raised TC. Those with a TC level between 5.0 and 5.9 mmol/L had the lowest death rate, which was 23% lower than those with a TC below 5.0 mmol/L. At higher values, the rate increased again.
For women the pattern is different. The higher the TC, the lower the risk of dying from all causes. Compared with those with a TC below 5.0 mmol/L, those with the highest TC levels were 28% less likely to die from all causes.
Table 1. Variation in mortality due to all causes and to cardiovascular diseases (CVD) with TC in men and women
| TC, Mmol/L (mg/100ml) | MEN | WOMEN | ||
| All-cause | CVD | All-cause | CVD | |
| <5.0 (<194) | 1.00 | 1.00 | 1.00 | 1.00 |
| 5.0-5.9 (194-228) | 0.77 | 0.80 | 0.92 | 0.90 |
| 6.0-6.9 (232-267) | 0.84 | 0.87 | 0.84 | 0.81 |
| >7.0 (>270) | 0.98 | 1.05 | 0.72 | 0.74 |
In a subsequent paper the research team provided the information for the different age ranges (3). This detailed break-down shows that as expected most of the deaths occur after the age of 60 years (Table 2). Although the optimum TC level for men aged 60-69 is in TC range 5.0 to 5.9 mmol/L, for those over 70 the lowest death rate is in the higher TC level of 6.0 to 6.9 mmol/L. For women it is very clear that the death rate for the over 60s decreases as the TC increases. For this age range it is evident that the highest death rates are for those with a TC level which is below 5.9 mmol/L. The relatively high death rates for those aged 60+ years at low TC values should also be noted.
Table 2. All-cause mortality rates (per 1000 person years) and TC levels at different age ranges
| MEN | ||||
| Age ranges | TC LEVELS, mmol/L(mg/100ml) | |||
| <5.0(<194) | 5.0-5.9(194-228) | 6.0-6.9(232-267) | >7.0(>270) | |
| 20-29 | 1.10 | 0.38 | 0.30 | 0.00 |
| 30-39 | 0.80 | 0.57 | 0.72 | 0.47 |
| 40-49 | 2.22 | 1.38 | 2.27 | 3.37 |
| 50-59 | 4.54 | 4.93 | 6.22 | 5.74 |
| 60-69 | 20.31 | 16.20 | 17.37 | 18.47 |
| 70-74 | 49.18 | 40.37 | 37.93 | 41.25 |
| WOMEN | ||||
| 20-29 | 0.35 | 0.30 | 0.24 | 0.60 |
| 30-39 | 0.31 | 0.43 | 0.82 | 0.69 |
| 40-49 | 0.89 | 1.85 | 1.69 | 1.12 |
| 50-59 | 2.95 | 3.59 | 3.53 | 3.79 |
| 60-69 | 22.31 | 10.32 | 10.47 | 9.51 |
| 69-74 | 31.46 | 22.50 | 21.58 | 19.23 |
The authors commented as follows:
‘’If our findings are generalizable, clinical and public health recommendations regarding the ‘dangers’ of cholesterol should be revised. This is especially true for women, for whom moderately elevated cholesterol (by current standards) may prove to be not only harmless but beneficial.’’
They went on to conclude:
‘’Our results contradict the guidelines’ well-established demarcation line (5 mmol /L) between
‘good’ and ‘too high’ levels of cholesterol. They also contradict the popularized idea of a positive, linear relationship between cholesterol and fatal disease. Guideline-based advice regarding CVD prevention may thus be outdated and misleading, particularly regarding many women who have cholesterol levels in the range of 5–7 mmol/Litre and are currently encouraged to take better care of their health’’.
The Netherlands
In the Netherlands, a study with residents in Leiden with an average age of 89 years, it was found that those with the highest TC levels had the lowest mortality, while those with low TC values had the highest mortality (4). Those with the high life expectancy was due to particularly low incidences of cancer and infection.
Hawaii
In the Honolulu Heart Programme the TC was measured between 1965 and 1968 in 7961 men of Japanese origin who were born between 1900 and 1919. During the period of this study the men were monitored on 3 occasions and there were 2072 deaths. The results (Table 3) confirm that in this group of men the death rate attributed to coronary heart disease is directly associated with the TC level. However for deaths from stroke there are high death rates for both high and low cholesterol values. For cancer, it is evident that the death rate is inversely related to the TC levels. In this study there were twice as many deaths due to cancer at low TC levels when compared with whose TC was above 6.98 mmol/L. For all-cause mortality the lowest death rates were found in the cholesterol range between 4.65 and 6.18 mmol/L (180 and 239 mg/100ml). The authors concluded that manipulation of TC levels below the range shown above would not be desirable if it was to result in an increased risk of death from cancer and other diseases (5).
Table 3. Relationship between death rate and total cholesterol for various causes of death
| AGE ADJUSTED MORTALITIES PER 1,000 PERSON-YEARS | ||||
| TC,Mmol/L(mg/100ml) | CHD | STROKE | CANCER | ALL CAUSES |
| <4.65 (<180) | 1.68 | 1.80 | 7.32 | 17.46 |
| 4.65-5.40(180-209) | 2.01 | 1.17 | 5.30 | 14.09 |
| 5.43-6.18(218-239) | 2.38 | 1.40 | 5.33 | 14.07 |
| 6.20-6.96(249-268) | 4.24 | 1.65 | 5.34 | 15.92 |
| >6.98 (>269 ) | 4.87 | 1.74 | 3.83 | 17.31 |
Austria
In Austria, 67,41men and 82,237 women aged 20–95 years were followed over a 15-year period (1985–1999) as part of the Vorarlberg Health Monitoring and Promotion Programme. It was found that in both men and women in the 50–64 and ?65 age groups, TC levels were a negative risk factor for all-cause mortality (6).
Finland
A study done in the Finnish city of Kuopio monitored 490 elderly persons aged over 75 (28% men) for 6 years. None of them were on cholesterol-lowering medication. Those with TC lower than 5mmol/L had a death rate that was double that of those who whose TC was greater than 6 mmol/L (7).
In another study done in Finland 623 people aged over 75 years were monitored for 17 years (8). The TC was monitored as well as lathosterol, which indicates cholesterol synthesis and sitosterol, which indicates cholesterol absorption. The results showed that TC declined in old age, and low cholesterol was associated with poor health and multi-morbidity. TC levels below 5.0 mmol/L were associated with accelerated all-cause mortality. Lathosterol and sitosterol both decreased with deteriorating health. Low lathosterol, sitosterol, and TC predicted mortality additively and independently of each other. When all three sterols were high the age expectancy was 9.9 years but when they were all low, it was reduced to 5.6 years. It was concluded that reduced synthesis and absorption of cholesterol, and low TC levels are associated with deteriorating health and indicate impaired survival in old age.
Conclusion
Without exception all-cause mortality is highest in those with the lowest levels of TC. In older people those with the highest cholesterol have the highest survival rates, irrespective of where they live in the world. The picture which emerges is totally consistent. The research which triggered the concern about heart disease was based almost entirely on middle-aged men and was restricted to heart disease. But what is so striking about all the studies cited here is that when the focus is on older people, which is when the vast majority deaths occur, and on all-cause mortality the perception of the risks associated with cholesterol are reversed. It is also highly significant that these results do NOT conflict with the research on middle-aged men and heart disease. The data from Honolulu confirm that in those involved in the study with low cholesterol there was a low death rate from heart disease but crucially the incidence of cancer was relatively high and demonstrates why it is vital to consider the big picture. The emphasis on TC and LDL cholesterol as risk factors was based on a complete failure to do so. There is absolutely no logical justification for advising people to lower their TC or their LDL cholesterol. On the contrary all the evidence which is now available indicates that that the higher the better. The results for women are quite exceptional and show consistently that those with the highest TC values invariably have the greatest life expectancy.
By contrast, we can be reasonably certain that the cholesterol lowering strategies which have been applied have not resulted in any benefit and probably have been damaging to health. In particular, the rationale for the use of drugs such as statins is totally destroyed by the evidence presented here. All the indications are that cholesterol is beneficial and the higher the better!
It really is astonishing and irresponsible for the authorities to continue the various programmes which still use TC as a risk factor for heart disease and push cholesterol-lowering strategies. It is time they were abandoned because they are not achieving anything positive and are almost certainly doing more harm than good, not to mention that there are a sheer waste of valuable resources.
REFERENCES
- https://www.karger.com/Article/Pdf/381654
- H Petursson et al (2012). Journal of Evaluation in Clinical Practice 18 (1) pp 159-168.
- H Petursson et al (2012). Journal of Evaluation in Clinical Practice 18 (1) pp 170-171.
- A W Weverling-Rijnsburger et al (1997) Lancet 350 pp 1119-1123
- G.Stemmerman et al (1991) Archives of Internal Medicine 151 pp.969-972
- Ulmer et al (2004) Journal of Womens Health 13 pp 41–53
- P Tuikkala et al (2010) Scandinavian Journal of Primary health Care 28 (2) pp 121-127
- R S Tivlis et al (2011) Annals Medicine 43 pp 292-301