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Atherosclerosis and Hypertension (High Blood Pressure)

Updated on 25th June 2009 by Dr Charles Tweed

ATHEROSCLEROSIS

If we are to die, ("Die, my dear? Why that's the last thing I'll do!" [Groucho Marx]) then the odds are it will be cardiovascular disease that will be the cause. Not only that, but the underlying process of atherosclerosis will also be the cause of your loss of confidence, function and symptoms in most cases. The central disorder is probably the cells that line the blood vessels – the vascular endothelium. Damage to these cells activates a series of chain reactions in the normal homeostatic mechanisms:

Activates the pro-inflammatory pathways
Activates platelets

These are normally protective processes, but chronic activation leads to undesirable results. Slowly the inflammation causes:

Thickening and stiffening of the blood vessels
Formation of fatty plaques
Furring up of arteries

The body tries to compensate for this by pumping harder and squeezing the blood through. Unfortunately this also causes more damage so a vicious cycle sets up. Eventually the blood supply and hence oxygen getting to the far end of the artery, can get too low to supply the target organ's basic needs. Alternatively, the plaques can rupture and rapidly block the artery completely.

Depending on what organ is being supplied, you can get away with almost no symptoms [if a little bit of muscles were to die] or you can drop dead [if it is a main vessel to the heart or brain]. The second deciding factor is if there is a collateral system – blood supply to the same area from a different artery. Unfortunately, the vessels that seem to have the worst collateral supply seem to be the most important ones – coronary arteries and carotid/cerebral arteries. This is a serious design flaw and if anyone can come up with a good way to fix this, please contact me and we can join Bill and Warren at the top of the Forbes one hundred. There are a number of distinct risk factors, some of which can be modulated.

High cholesterol
Diabetes
High blood pressure
Obesity
Smoking
A family history of aneurysm or early heart disease

I am unable to offer you any advice on how to alter your inherited genetic risk, although genetic manipulation is feasible within our lifetimes. The risks of smoking have been discussed elsewhere and are plain for everyone to see. Obesity is set to become an increasing issue. I have covered most of the relevant issues in the diet and exercise sections. If you are trying to lose weight, I am afraid it a question of hard discipline, a long horizon and re-organising the priorities in your life. Please do not go on a diet, they never work long-term, and do not restrict yourself to unrealistic food groups. The resulting rebound weight gain is hard to cope with psychologically.

LIPID PROFILES

One of the problems that contribute to atherosclerosis is the lipid cholesterol. The inflamed vessel wall attracts cholesterol molecules which become oxidised and infiltrate into the vessel wall, get eaten by defence cells called macrophages which then get a bad case of indigestion and transform into a foam cell. It is these foam cells that make up much of the fatty plaque that can cause all the mischief. It appears that oxidised LDL is the real culprit. HDL is the good cholesterol which actually takes cholesterol from the peripheries to the liver, helping solve the problem. Therapeutic options, therefore, can include:

Lowering bad LDL cholesterol
Raising good HDL cholesterol
Decreasing oxidative stress
Decreasing triglycerides

It will come as no surprise that the usual options of regular physical exercise and healthy eating will address all of these to some degree. However, for many people these will not be enough, or they may fail to do them adequately. The next step is either drugs, supplements or a combination of both. On top of this the next step is to take Niacin to increase your good Hdl. Please see the Assessment of Niacin for more information.

HYPERTENSION

High blood pressure is called the silent epidemic. Most people who are hypertensive have been told they have it by their doctor, who might have picked it up on a routine check. Many people, however, are completely unaware they have it and may have had it for many years.

If left untreated, hypertension hugely increases the risks of developing numerous other medical conditions:

Heart disease.
Strokes.
Kidney failure.
Heart failure.

How dangerous is it? Well, look at the following table and it becomes pretty clear that left untreated, high blood pressure is not a good thing.

Blood pressure (mmHg)	Life expectancy (years)
120/80	76
130/90	67
140/95	62
150/100	55

Hypertension may occur in isolation but is often as part of a heterogeneous condition that includes the following:

Abnormal blood lipids.
Insulin resistance and type II diabetes.
Central obesity.
Kidney function abnormalities.
A tendency to form blood clots.
A pro-inflammatory state.

Hypertension is not diagnosed on one visit. If your blood pressure is raised on your first appointment, it will be checked several times over the next few weeks and if it remains persistently raised will then be treated. Sometimes you will have blood pressure monitoring done over a 24 hour period with a remote device.

People may have their blood pressure treated more aggressively if they have other health problems. The mainstay of treating hypertension remains drug therapy. Often several different agents are used in combination. However, there are many things you can do to lower your blood pressure yourself.

Lose weight. Most people with high blood pressure are overweight.
Reducing your weight down to your ideal weight improves most measures of cardiac function, reduces insulin levels, inflammation and salt retention.
Stop smoking. Some people will get away with smoking without too much ill health. If you are hypertensive, you are not one of those people.
Limiting caffeine consumption. Caffeine causes the blood vessels to constrict and increases levels of noradrenaline, both are to be avoided if you have high blood pressure.
Limiting alcohol consumption. More than 2 standard drinks per day elevates blood pressure.
Exercise. 30-60 minutes per day of aerobic exercise and progressive anaerobic exercise x 3 per week. Aim for a heart rate of 60 – 80 % of maximal (220 – age). Incorporating regular exercise into your life can lower blood pressure by 10 mmHg.
Stress modification. Relaxation techniques, meditation.
Avoid drugs that can increase BP. Oral contraceptive, anti-inflammatory drugs (ibuprofen, diclofenac), anabolic steroids among many, many others.
Nutritional modification. See following section.
Micronutrients in the treatment and prevention of hypertension.

Drugs are used to treat the actual blood pressure but this is only part of the picture. It is increasingly being recognised that the reason that the normal biofeedback loop is wrong is due to damage and dysfunction of the cells that line the blood vessels. Our diet has changed beyond recognition in the last hundred years and even more so if we go back several thousand years. Our bodies have been adapted over millennia to certain conditions – and they are not the conditions we are subjecting them to now.

The well constructed and run DASH and DASH II diets demonstrated that dietary modification can reduce blood pressure by up to 11.5/6.8 mmHg, and can be as effective as a drug. The DASH diets are relatively hard to stick to as they include a very high consumption of fruit and vegetables and very little salt/sodium. The following is a brief list of interventions that you can make to prevent high blood pressure. In those who already have high blood pressure it may allow you to decrease the number and dose of drugs you are on, or even come off treatment altogether.

Minerals

Reduce sodium consumption to less than 2400mg. More restrictive diets can be even more effective. Increase potassium consumption to greater than 120meq per day. Either through potassium rich foods or by supplementation. Increase magnesium consumption by supplementation or diet by 500-1000mg per day. Increase calcium – particularly if you have a high sodium intake are elderly diabetic or are a postmenopausal woman.

Food groups

Fats – no surprise here! Olive oil – greater than 4 table spoons per day. Fish oils 3-4 grams per day. Avoid trans fatty acids altogether and consume less n-6 oils to maintain a ratio of omega-3:omega-6 at ~3:1. These changes may reduce BP by up to 5-8mmHg. Foods you can eat to achieve this are nuts, lean meats particularly from wild animals and of course, cold water fish.
Protein – a high protein intake from non-animal sources is associated with a lower blood pressure. High protein foods include sardines and lean fish, lentils and other legumes/pulses and soy. Alternatively you can consume pre-prepared things such as whey protein.
Carbohydrates - more a case of not eating processed foods and refined carbohydrates, and having a high fibre diet.

Coenzyme Q10

Coenzyme Q10 (CoQ10) is not a vitamin as we can manufacture it ourselves. It is considered a conditionally essential nutrient in cardiovascular disease and used to help support multiple other enzymes in a huge number of different processes and is essential for life. Levels of CoQ10 slowly decrease thoughout life and mitochondrial function (the cellular powerplants) declines in a similar fashion. A summary of the points:

Considered a conditionally essential nutrient in cardiovascular disease. [1]
Important for the prevention and treatment of cardiovascular disease including hypertension, hyperlipidemia, coronary artery disease, and even heart failure. [2]
Decreased levels of muscle CoQ10 are thought to play a role in statin induced myopathy. [3]
Levels of CoQ10 have been found to decrease when taking HMG-CoA reductase inhibitors, gemfibrozil, Adriamycin, and certain beta blockers. [2]
When taken concomitantly with vitamin E, CoQ10 has been found to improve both cardiac and skeletal muscle bioenergetics as well as heart function. [4]

Safety

CoQ10 has an excellent safety record with no reports of significant side effects. [5]
Doses as high as 1200 mg/day have been used for a period of 16 months without adverse side effects. [6]
Concomitant use of warfarin with CoQ10 may decrease the anticoagulant effect of the drug.
Clotting time should therefore be monitored regularly, particularly within the first two weeks of taking CoQ10. [7]

39% of people with hypertension have a coQ10 deficiency as compared with 6% of normal people. Numerous trials have shown a very impressive reduction in blood pressure in response to taking CoQ10. When doses of between 100 and 200mg are used, blood pressure can drop by around 15/10 mmHg. It also seems to reduce total and bad cholesterol (LDL), as well as help reverse insulin resistance.

We recommend a starting dose of between 60-100mg of CoQ10 increasing up to 200mg if needed. There do not appear to be any significant short or long term side effects.

Alpha Lipoic Acid

For a full discussion of Alpha Lipoic Acid, please see the Assessment of Alpha Lipoic Acid.

Considered a conditionally essential nutrient in cardiovascular disease and associated risk factors such as hypertension, hyperlipidemia, and elevated lipoprotein(a). Alpha Lipoic Acid (ALA) acts as a cardioprotectant by inducing heme-oxygenase in smooth muscle cells. Protects against cardiac lipotoxicity. The summary is as follows:

Considered a conditionally essential nutrient in cardiovascular disease and associated risk factors such as hypertension, hyperlipidemia, and elevated lipoprotein(a) [1]
ALA acts as a cardioprotectant by inducing heme-oxygenase in smooth muscle cells. [8] Protects against cardiac lipotoxicity. [9]
Works synergistically with pioglitazone to restore PPAR-gamma levels in cardiovascular tissue and thus reduce oxidative stress associated with insulin resistance and hypertension. [10]
Being a fat and water soluble antioxidant ALA is able to cross the blood brain barrier.
ALA is also involved in the recycling of the antioxidant glutathione (GSH) and acts as a redox regulator. [11]
In the animal model, ALA has demonstrated neuroprotectant activity by reducing inflammation, enhancing memory and providing anti-excitotoxic for the brain. [11]
Provides protection against neurological disorders by helping to prevent oxidative damage to the central nervous system. ALA also supports cell membranes by interacting with vitamin C and GSH and as such is hypothesized to recycle vitamin E. [15]
ALA (in combination with vitamin E) helps restore reduced SOD levels and endothelial vascular dysfunction as a consequence of cyclosporine therapy. [13]

Safety

ALA is considered a safe antioxidant with minimal side effects.
Allergic skin reactions have been one of the few reported adverse effects.
In animal studies, the LD50 was 400-500mg/kg.
A vitamin B1 deficiency in rats given ALA resulted in toxicity at 20mg/kg, but was prevented with concomitant vitamin B1 administration.
To date there is insufficient evidence to safely recommend this antioxidant during pregnancy[14].
In rats, ALA in combination with vitamin E has been increases bleeding tendency via inhibition of the intrinsic coagulation pathway (but doesn’t affect prothrombin time). [14]
ALA in combination with EPA has been found to protect against lipemic induced oxidative injury. [16]

AOR R(+) Lipoic Acid contains 450mg in three capsules.

Red Yeast Rice Extract

Has a lipid lowering effect by inhibiting cholesterol biosynthesis in the liver, thus it functions similarly to HMG-CoA reductase inhititors.
The active constituents of red yeast rice are the monacolins which have all been found to inhibit HMG-CoA reductase. [17]
Has been shown to reduce total cholesterol, LDL cholesterol and triglycerides while increasing HDL cholesterol in those with hyerlipidemia. [18]
The same beneficial effects have also been observed in those with hypercholesterolemia.
In healthy volunteers, red yeast rice extract has lowered total cholesterol and LDL levels, but had no impact on HDL cholesterol. [19]

Safety

Animal studies have shown no toxicity and human trials of red yeast rice have not resulted in any changes to liver or kidney function tests.

A reduction in tissue levels of CoQ10 has been noted when taking red yeast rice extract. [20, 21]
Supplementation of CoQ10 is therefore advised with long term red yeast rice ingestion.

As a measure of precaution, it is advised to avoid red yeast rice with medications known to be contraindicated with lovastatin. This includes the following drugs; gembibrozil, cyclosporin, azole antifungals, protease inhibitors, erythromycin, clarithromycin and nefazodone[17]. Contra-indicated in renal transplant patients on hypolipidemic medication. [23]
A study by Kusus et al suggests that drugs that act as substrates for the cytochrome P450 3A4 pathway and/or P-glycoprotein substrates should be avoided to reduce rhabdomyolysis caused by 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors. [24]

Resveratrol

For a full discussion of Resveratrol, please see the Assessment of Resveratrol.

The polyphenol compounds isolated in resveratrol are thought in part to explain low incidence of cardiovascular morbidity in the Mediterranean known as the “French Paradox".
Resveratrol exerts both anti-oxidant and anti-inflammatory actions in a number of disease processes. [25]
Its therapeutic actions include; anti-platelet, anti-inflammatory, anticancer, anti-mutagenic and antifungal. [26]
Other therapeutic properties include free radical scavenger, heavy metal chelator. In the role of cardiovascular support, resveratrol helps reduce lipid peroxidation, as well as oxidation and nitration of platelets and plasma proteins. [26]

Safety

No adverse side effects have been noted for resveratrol.
In vitro studies suggest that high doses of resveratrol may inhibit platelet aggregation. Individuals taking anti-coagulant medication are advised to exercise caution when supplementing. [27]
In animal studies, supplemental resveratrol has been shown to increase triiodthyronine (T3) levels. [28]

It would be necessary to take ~300mg per day to achieve doses similar to those given in studies. Hence you would need to purchase the AOR Acta-Resveratrol which has 300mg in three capsules plus other agents to maximise absorption.

Hawthorn

Plays a role on the prevention of cardiovascular disease including hyperlipidemia, hypertension and congestive heart failure[29]. [29]
The active components of the herb exert their effects on the endothelial cells with subsequent release of nitric oxide (NO) and relaxation of blood vessels. This in turn lowers arterial blood pressure and enhances coronary blood flow. [30]
Possesses hypolididemic properties by protecting LDL cholesterol from copper II and free radical oxidation. [31]
Reduces total cholesterol, specifically LDL cholesterol and triglycerides without affecting HDL cholesterol. [32]
Studies have also consistently demonstrated Hawthorn’s ability to improve exercise tolerance. [33]

Safety

Considered a safe herb without any major adverse side effects. Dosing at 900 mg/day has produced mild and infrequent side effects in less than 1.5% of participants. [34]
Review articles have noted occasional gastro-intestinal complaints and sedative effect, and in one article rashes were reported. Clinical studies however have not reported such effects. [33]
Hawthorn is safe to use in patients with mild heart failure in conjunction with conventional medication.
Therapeutic efficacy requires at least 4-6 weeks of continued administration. [33]

Artichoke extract (Cynara scolymus)

Modulates endothelial function, helps prevent atherosclerosis and coronary heart disease. [35]
Aids in the inhibition of cholesterol biosynthesis and reduces LDL oxidation[36]. [36]
Artichoke has been found to lower total cholesterol and LDL cholesterol in those with hyperlipoproteinemia. [19]
This botanical also has a beneficial effect on the LDL:HDL ratio, and in one study lowered by over 20%. [35]
In vitro studies have shown that artichoke reduces oxidative stress in endothelial cells by inhibiting free radicals stimulated by inflammatory cytokines such as TNF alpha, and IL-1 Beta. [37]
The flavonoids in artichoke are thought to play a role in up regulating endothelial nitric oxide synthase (eNOS), an enzyme with anti-thrombotic and anti-atherosclerotic effects in the vasculature. [38]

Safety

A very safe and well tolerated herb with virtually no side effects.
To date, studies have shown no evidence of adverse interactions with any conventional medications. [35]
In one study, flatulence, hunger and weakness were noted in less than 2% of participants. [19]

Taurine

While human studies are limited, animal and in-vitro studies show taurine to be an important nutrient in cardiovascular disease. [1]
Derived cysteine and methionine, taurine is the most abundant amino acid in cardiac muscle constituting up to 50% of the total amino acid pool. [39]
Reduces cholesterol and has been found to lower blood pressure. [40]
Taurine also doubles as an antioxidant and is able to react with aldehydes thus inhibiting the alteration of LDL by malondialdehyde. [41]
Regulates intracellular calcium thus protects the heart from myocardial damage as intracellular calcium imbalances can lead to myocardial damage and cell death. [42]
Prevents cardiac arrhythmias possibly by regulating the potassium flux in cardiac muscle cells. [43]

Safety

Considered safe in high doses in both human and animal studies.
Doses of 1500 mg in some epileptic patients results in headaches, nausea, dizziness, and gait disturbances. [42]
In individuals with psoriasis doses of 2000 mg per day lead to intense itchiness that commenced within an hour and continued for 24 hours. [44]

Lycopene

For a full discussion of Lycopene, please see the Assessment of Lycopene.

Lycopene the subject of increasing amounts of study, and not just for cardiovascular disease. It is an active ingredient found primarily in tomatoes, and its concentration is increased by cooking – plus, it remains stable for long periods of time. Lycopene levels are inversely correlated with the development of cardiovascular disease and hypertension. In fact in one study they were far more strongly associated with good health than any of the other vitamins checked including Vitamin C, Vitamin E and beta-carotene. There have been several good intervention studies looking at high blood pressure. On average a significant reduction of around 10/7 mmHg is achievable with 10mg of lycopene extract per day. Lycopene is also found in water melon, guava, pink grapefruit and red peppers. It's effect may be increased by consuming it together with broccoli. A summary is as follows:

Anti-oxidant, hypocholestremic, anti-atherogenic, anti-carcinogenic.
A potent antioxidant found to be twice as effective as beta-carotene and 10 times more effective than vitamin E in quenching the free radical singlet oxygen. [45] Protects against oxidative damage to proteins, lipids and DNA. [46]
Helps reduce cholesterol by inhibiting HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase. [47]
Found to be independently protective against myocardial infarction risk when compared with the carotenoids alpha-carotene and beta-carotene.
Associated with a reduced risk of a number of cancers including prostate, breast, stomach and lung cancer. [48]
Also helps protect against the development of prostate cancer in health prostate tissue. [49]

Safety

Considered safe, non-toxic, and without side effects.
Dosage in studies has varied between 6-60 mg with 6 mg being ingested for protection against the development of prostate cancer. [50]

AOR Lycopene Ultra, contains 20mg per capsule.

Vitamin C

There is a lot of circumstantial evidence to suggest Vitamin C is important in maintaining a low blood pressure. Certainly vit C consumption and plasma levels are inversely correlated with blood pressure, heart disease and stroke, and multiple small studies suggest it can be therapeutic in populations with established hypertension.

Vitamin C is known to have important roles in intermediate steps that will reduce blood pressure and heart disease.

Conclusive proof, in the form of intervention studies, is still somewhat missing. Trials have been done to see if introducing vitamin C will actually lower BP in a “gold standard” setting of a prospective, randomised, double blind controlled trial. Unfortunately, these have shown conflicting results. It is not clear why. Perhaps, there are too many confounding factors.

It is likely that vitamin C is a necessary part of blood pressure control and it certainly does not appear to be harmful. We recommend consuming between 250 and 500mg of vitamin C per day until further evidence is forthcoming. We also strongly recommend consuming foods that are high in vitamin C such as blackcurrants, red peppers papaya, broccoli and citrus fruits.

Vitamin E

The study of Vitamin E is mired in controversy, and it isn’t getting any clearer.

It was initially thought that Vitamin E was the poster boy of cardiovascular disease prevention. It seemed to possess potent effects in improving most of the intermediate steps in the generation of all the things that go wrong.

Unfortunately life is far more complicated than that. It transpires that Vitamin E is not just one substance but a collection of 8 different related structures. Scientist started off looking at the most promising one alpha-tocopherol. This was abundant and had startling effects in the laboratory and in the mouse model. Unfortunately, it doesn’t seem to have the same effects in humans, indeed there is a suggestion that in high dosages of 800iu or greater it may actually be harmful. Next they looked at a mix of alpha and gamma-tocopherol, combinations of Vitamin A, E and beta-carotene, and now they are looking at mixed tocopherols. The latest reports suggest it may be the tocotrienols that are of most benefit in human health.

The take home message from this is:

Don’t take alpha-tocopherol in isolation and certainly not at high dosage (>800iu).
Mixed tocopherols, especially in combination with vit A, C, E and betacarotene may be of benefit, but probably are not.
We watch this space closely on updates on work with the tocotrienols.
Supplementation in the form of mixed natural Vitamin E is clearly the best way of consuming it. However, it is unfortunately rather expensive.
Good sources of vitamin E are nuts, liver, whole grains, eggs and leafy greens.

Vitamin B6

Both animals and humans that are deficient in B6 (pyridoxine) have high blood pressure, and supplementing with B6 reverses this. Intervention studies in hypertensive humans are limited but suggest an improvement in BP measurements. B6 is necessary in many steps that are required to maintain a normal blood pressure. It is harmless in doses of up to 200mg per day, and therefore we recommend taking it.

Garlic

Several clinical trials have shown a modest reduction in blood pressure of about 5mmHg. Populations that consume a lot of garlic have a lower incidence of high blood pressure and cardiovascular disease. It is the allicin content of garlic that appears to be the most active component. Unfortunately, this is completely inactivated by 15-20 minutes of cooking. Crushing garlic helps prevent the destruction by heating. We recommend several cloves of garlic a day or taking aged garlic extract. Clearly, this dosage should be moderated if there are romantic or social issues to consider!

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