HEALTH – HEART – CHRONIC INFLAMMATION


6 RESEARCH ARTICLES + 1 GRAPHIC



Aseem Malhotra; Rita F Redberg; Pascal Meier
INTRODUCTION
– Coronary heart disease is a chronic inflammatory condition
– Risk can be effectively reduced from healthy lifestyle interventions

– Despite popular belief among doctors and the public, the conceptual model of dietary saturated fat clogging a pipe is just plain wrong
– A landmark systematic review and meta-analysis of observational studies showed no association b/n saturated fat consumption and:
(1) all-cause mortality
(2) coronary heart disease (CHD)
(3) CHD mortality
(4) ischaemic stroke
(5) type 2 diabetes in healthy adults
– Similarly in the secondary prevention of CHD there is no benefit from reduced fat, including saturated fat, on myocardial infarction, cardiovascular or all-cause mortality
– It is instructive to note that in an angiographic study of postmenopausal women with CHD, greater intake of saturated fat was associated with less progression of atherosclerosis whereas carbohydrate and polyunsaturated fat intake were associated with greater progression
PREVENTING THE DEVELOPMENT OF ATHEROSCLEROSIS IS IMPORTANT BUT IT IS ATHEROTHROMBOSIS THAT IS THE REAL KILLER
– The inflammatory processes that contribute to cholesterol deposition within the artery wall and subsequent plaque formation (atherosclerosis), more closely resemble a ‘pimple’ (figure 1)
– Most cardiac events occur at sites with <70% coronary artery obstruction and these do not generate ischaemia on stress testing
– When plaques rupture (analogous to a pimple bursting), coronary thrombosis and myocardial infarction can occur within minutes
– The limitation of the current plumbing approach (‘unclogging a pipe’) to the management of coronary disease is revealed by a series of randomised controlled trials (RCTs) which prove that stenting significantly obstructive stable lesions fail to prevent myocardial infarction or to reduce mortality


Figure 1

Figure 1: Lifestyle interventions for the prevention and treatment of coronary disease


DIETARY RCTs WITH OUTCOME BENEFIT IN PRIMARY AND SECONDARY PREVENTION
– In comparison with advice to follow a ‘low fat’ diet (37% fat), an energy-unrestricted Mediterranean diet (41% fat) supplemented with at least four tablespoons of extra virgin olive oil or a handful of nuts (PREDIMED) achieved a significant 30% (number needed to treat (NNT)=61) reduction in cardiovascular events in over 7500 high-risk patients
– Furthermore, the Lyon Heart study showed that adopting a Mediterranean diet in secondary prevention improved hard outcomes for both recurrent myocardial infarction (NNT=18) and all-cause mortality (NNT=30), despite there being no significant difference in plasma low-density lipoprotein (LDL) cholesterol between the two groups
– It is the alpha linoleic acid, polyphenols and omega-3 fatty acids present in nuts, extra virgin olive oil, vegetables and oily fish that rapidly reduce inflammation and coronary thrombosis.6
– Both control diets in these studies were relatively healthy, which make it highly likely that even larger benefits would be observed if the Mediterranean diets discussed above were compared with a typical western diet
LDL CHOLESTEROL RISK HAS BEEN EXAGGERATED
– Decades of emphasis on the primacy of lowering plasma cholesterol, as if this was an end in itself and driving a market of ‘proven to lower cholesterol’ and ‘low-fat’ foods and medications, has been misguided
– Selective reporting may partly explain this misconception
– Reanalysis of unpublished data from the Sydney Diet Heart Study and the Minnesota coronary experiment reveal replacing saturated fat with linoleic acid containing vegetable oils increased mortality risk despite significant reductions in LDL and total cholesterol (TC).7
– A high TC to high-density lipoprotein (HDL) ratio is the best predictor of cardiovascular risk (hence this calculation, not LDL, is used in recognised cardiovascular risk calculators such as that from Framingham)
– A high TC to HDL ratio is also a surrogate marker for insulin resistance (ie, chronically elevated serum insulin at the root of heart disease, type 2 diabetes and obesity)
– And in those over 60 years, a recent systematic review concluded that LDL cholesterol is not associated with cardiovascular disease and is inversely associated with all-cause mortality.8
– A high TC to HDL ratio drops rapidly with dietary changes such as replacing refined carbohydrates with healthy high fat foods
A SIMPLE WAY TO COMBAT INSULIN RESISTANCE (CHRONICALLY HIGH LEVELS OF SERUM INSULIN) AND INFLAMMATION
– Compared with physically inactive individuals, those who walk briskly at or above 150 min/week can increase life expectancy by 3.4–4.5 years independent of body weight.9
– Regular brisk walking may also be more effective than running in preventing coronary disease
– And just 30 min of moderate activity a day more than three times/week significantly improves insulin sensitivity and helps reverse insulin resistance (ie, lowers the chronically elevated levels of insulin that are associated with obesity) within months in sedentary middle-aged adults
– This occurs independent of weight loss and suggests even a little activity goes a long way
– Another risk factor for CHD is environmental stress.
– Childhood trauma can lead to an average decrease in life expectancy of 20 years
– Chronic stress increases glucocorticoid receptor resistance, which results in failure to down regulate the inflammatory response
CONCLUSION
– Combining a complete lifestyle approach of a healthful diet, regular movement and stress reduction will improve quality of life, reduce cardiovascular and all-cause mortality.10
– It is time to shift the public health message in the prevention and treatment of coronary artery disease away from measuring serum lipids and reducing dietary saturated fat
– Coronary artery disease is a chronic inflammatory disease; it can be reduced effectively by walking 22 min a day and eating real food
– There is no business model or market to help spread this simple yet powerful intervention


ANALYSIS OF RECOVERED DATA FROM THE MINNESOTA CORONARY EXPERIMENT (1968-73)


OBJECTIVE
– To examine the traditional diet-heart hypothesis through recovery and analysis of previously unpublished data from the Minnesota Coronary Experiment (MCE)
– To put findings in the context of existing diet-heart randomized controlled trials through a systematic review and meta-analysis
DESIGN
– The MCE (1968-73) is a double blind randomized controlled trial designed to test whether replacement of saturated fat with vegetable oil rich in linoleic acid reduces coronary heart disease and death by lowering serum cholesterol
– Recovered MCE unpublished documents and raw data were analyzed according to hypotheses prespecified by original investigators
– Further, a systematic review and meta-analyses of randomized controlled trials that lowered serum cholesterol by providing vegetable oil rich in linoleic acid in place of saturated fat without confounding by concomitant interventions was conducted
– Unpublished documents with completed analyses for the randomized cohort of 9423 women and men aged 20-97; longitudinal data on serum cholesterol for the 2355 participants exposed to the study diets for a year or more; 149 completed autopsy files
(1) Serum cholesterol lowering diet that replaced saturated fat with linoleic acid (from corn oil and corn oil polyunsaturated margarine)
(2) Control diet was high in saturated fat from animal fats, common margarines, and shortenings
MEASUREMENTS
1. Death from all causes
2. association between changes in serum cholesterol and death
3. coronary atherosclerosis and myocardial infarcts detected at autopsy
RESULTS
– The intervention group had significant reduction in serum cholesterol compared with controls (mean change from baseline
– Kaplan Meier graphs showed no mortality benefit for the intervention group in the full randomized cohort or for any prespecified subgroup
– There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol in covariate adjusted Cox regression models
– There was no evidence of benefit in the intervention group for coronary atherosclerosis or myocardial infarcts
– Systematic review identified five randomized controlled trials for inclusion; In meta-analyses, these cholesterol lowering interventions showed no evidence of benefit on mortality from coronary heart disease or all cause mortality
CONCLUSIONS
– Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to lower risk of death from coronary heart disease or all causes
– Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid


INTAKE OF SATURATED AND TRANS UNSATURATED FATTY ACIDS AND RISK OF ALL CAUSE MORTALITY, CV DISEASE AND TD2 – 2015


S. Anand, McMaster University
OBJECTIVE
– To systematically review associations between intake of saturated fat and trans unsaturated fat and all cause mortality, cardiovascular disease (CVD) and associated mortality, coronary heart disease (CHD) and associated mortality, ischemic stroke, and type 2 diabetes
DESIGN
– Systematic review and meta-analysis.
RESULTS
– Saturated fat intake was not associated with all cause mortality, CVD mortality, total CHD, ischemic stroke or type 2 diabetes; There was no convincing lack of association between saturated fat and CHD mortality
– Total trans fat intake was associated with all cause mortality, CHD mortality, and total CHD but not ischemic stroke or type 2 diabetes
– Industrial, but not ruminant, trans fats were associated with CHD mortality and CHD
– Ruminant trans-palmitoleic acid was inversely associated with type 2 diabetes
– The certainty of associations between saturated fat and all outcomes was “very low.”
– The certainty of associations of trans fat with CHD outcomes was “moderate” and “very low” to “low” for other associations
CONCLUSIONS
– Saturated fats are not associated with all cause mortality, CVD, CHD, ischemic stroke, or type 2 diabetes, but the evidence is heterogeneous with methodological limitations
– Trans fats are associated with all cause mortality, total CHD, and CHD mortality, probably because of higher levels of intake of industrial trans fats than ruminant trans fats
– Dietary guidelines must carefully consider the health effects of recommendations for alternative macronutrients to replace trans fats and saturated fats


2016 – LACK OF ASSOCIATION OR AN INVERSE ASSOCIATION BETWEEN LOW-DENSITY-LIPOPROTEIN CHOLESTEROL AND MORTALITY IN THE ELDERLY


2014 – DIETARY FATTY ACIDS IN THE SECONDARY PREVENTION OF CORONARY HEART DISEASE


2013 – CORONARY ARTERY DISEASE AS CLOGGED PIPES: A MISCONCEPTUAL MODEL


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