Cadiovascular Disease

 

Cardiovascular disease refers to the disease of the heart and blood vessels. Although we continue to learn more about this disease, it continues to be one of the top killers in the United States. Today, I'd like to take a look at what integrative and functional medicine have to offer.

Cardiovascular disease is a multifaceted problem that results in life threatening cases of heart attack, embolism, and stroke. These different events are all caused by a problem in the arteries. As we understand it currently, molecules that carry cholesterol called low-density lipo-proteins (or LDL) get stuck under the linings to our blood vessels. As they build up, immune cells try to consume them. Their high cholesterol content causes the immune cells to foam up. As more cholesterol builds up in the vessel lining, bulges begin to obstruct the flow of blood and (perhaps more importantly) red blood cells. This fatty build up can become calcified, making the vessel brittle. Brittle and bulging blood vessels become anchors to platelets which can accumulate into a clot, further blocking the flow of blood. If a platelet clump breaks off in an artery, it could potentially flow into an arteriole or capillary where it can block the flow of blood completely.

Whether by bulging walls or clots, the problem boils down to the lack of oxygen flowing to important cells such as in the heart, brain, or lungs. The perfect solution to this complex problem has yet to be found. However, current western medicine has leaned heavily into lowering LDL in the blood, reducing the body's ability to form clots, and physically pushing the artery walls back open. Very large, well-studied trials demonstrate the effectiveness of this tactic.

One of the points that makes this approach questionable is the LDL lowering medication. We know that atorvastatin 80mg is meant to decrease a patient's LDL by more than 50%. However, we don't have much solid evidence as to how low someone's LDL needs to be. We know that some of these LDL molecules are part of the problem, but we don't know how or why lowering them reduces risk. And we don't have a way of targeting the kind of LDL molecules that seem to be the biggest problems among the variety of LDL molecules there are. In fact, we know statin drugs do more than just reduce a patient's LDL levels. The beneficial effects of a given drug other than the targeted one are called pleiotropic effects. Statin drugs' pleiotropic effects include being anti-inflammatory to blood vessels. Like many complex problems, there are likely multiple solutions that affect it in different ways.

Let's see what complementary and alternative medicine has to offer cardiovascular disease. I will specifically look at effects on cholesterol build up, artery calcification, clotting, and blood pressure.

Diet is always a good place to start when it comes to health. There is a growing body of significant evidence that suggests as diets more closely reflect the vegan lifestyle, the cardiovascular benefits increase. A meta analysis published in June of 2017 in the International Journal of Epidemiology found positive correlations between eating more fruit and vegetables to better outcomes for cardiovascular disease, cancer, and "death for any reason". If found to be a causal relationship, millions of lives could be extended by increasing fruit and vegetable intake to 500 grams a day. It was observed that apples and pears, citrus fruits, green leafy vegetables, cruciferous vegetables, and salads all had better outcomes against cardiovascular disease for patients taking more of them. It is certainly possible that people who are more apt to eating these foods do other things that benefit their heart health, so we cannot conclusively say from this analysis that eating more fruit and vegetables will improve cardiovascular health directly.

I found another small study comparing low-carb vegan diet with a high-carb vegetarian diet. Although it was only 39 overweight participants, it was supported on a base of some excellent research. The vegetarian diet did see decreases in weight and LDL, but there were even more significant decreases in the vegan arm. They allowed participants to chose from a selection of foods, but they also provided all foods for the course of the study. This reflects more closely what people would choose to eat naturally, but there may be a hurdle in buying and preparing appropriate foods that was not reflected in the study. Cohort studies preceding this research supports their findings.

While we're on the subject of lifestyle modifications, it almost goes without saying that smoking cessation is the single thing a current smoker can do to improve cardiovascular outcomes. According to the CHANCES consortium of prospective cohort studies published in 2015, there is a dose dependent relationship between smoking and cardiovascular disease. This meta analysis found that smoking cessation can have a positive impart on life expectancy even if initiated after the age of 60, and the longer a person has lived passed the cessation date, the smaller their risk is of cardiovascular events becomes.

Stress reduction and exercise are popular non-pharmacological ways of managing cardiovascular health. Even patients who have coronary heart disease have demonstrated cardiovascular and psychological benefits using exercise and mindfulness practices. Several small trials point to tai chi, chigong, and yoga as gentle and even beneficial for blood pressure lowering. Specifically, there was a study that took 75 participants in 3 arms - yoga with postures, yoga without postures, and wait list (as the control) group. Ultimately, the yoga without postures showed benefit over the other two arms in ambulatory systolic blood pressure.

I discussed in a previous episode about the benefits of dry sauna. Several studies have been done that

paint an interesting picture of its benefits. Although not conclusive, evidence suggests that sauna does decrease blood pressure immediately following a short sauna bath. A large retrospective study also found a correlation between men who regularly sauna bathed and blood pressure within normal limits. Another study followed over 2000 Finnish men who sauna bathed regularly for over 20 years. This study found an inverse relationship between frequency and duration of sauna bathing with negative cardiovascular outcomes such as sudden cardiac death and fatal cardiovascular disease. Efforts were made to stratify participants against a number of confounding factors. Mechanistically, sauna bathing is meant to be a relaxing activity which can in itself reduce stress, but there may be additional benefits. Recorded biomarkers suggest similar benefit to physical activity such as improved endothelial function, reduced oxidative stress, lower inflammation and improved arterial stiffness. There are chemical changes in hormone levels including norepinephrine, cortisol, renin, and growth hormone. More research needs to be explored to determine causality and the exact science of why Finnish sauna has shown benefit, but it seems that participating in dry sauna can be enjoyable and beneficial.

I'd like to move on to supplements. There was not a lot of good evidence that suggests taking supplemental vitamins B, C, or E made an impact on cardiovascular outcomes. It is possible that there are morbidity benefits that have not been explored very well, however, mortality benefit was not demonstrated across a number of meta analyses. I will say that meta analyses do tend toward null hypotheses (which means they favor the idea that the proposed interventions are not effective). I did find some interested trials that showed benefit for some other supplements, however. For example, a study in Sweden was performed using 443 participants with the mean age of 78. They were given CoQ10 200mg and Selenium yeast 200mcg daily or a matching placebo for 4 years. The study followed up with these patients after 12 years from initiation and found a significant decreased risk of cardiovascular mortality among patients treated with these supplements. Although the study was small compared to other CV trials, it provides enough evidence to suggest further study. I am particularly intrigued by the mean age. By the end of the intervention, this would have been close to average life expectancy. I feel like there is significance in the fact that this trial was able to find benefit 8 years later.

Magnesium has also demonstrated blood pressure lowering effects. In a meta analysis including 34 trials and 2028 participants, the data demonstrates a causal relationship. Supplementing with magnesium 300mg for at least 1 month can lower blood pressure by an average of 2.0 mmHg systolic and 1.78 diastolic.

Now I'd like to address herbal products. I would highly recommend reviewing the episode on garlic for cardiovascular benefits. Basically, patients taking aged garlic extract were found to have less calcification and healthier fat deposits around their coronary arteries. There is also a small trial relaying the benefits of ginger for cardiovascular health. 36 patients on dialysis were randomly assigned to receive either 1000mg of ginger or a placebo daily for 10 weeks. Patients receiving ginger had significantly reduced triglyceride levels compared with placebo. I should note that cholesterol levels remained unchanged during the course of this trial.

The recent VITAL trial demonstrates that although vitamin d3 and omega-3 fish oils could potentially have other benefits, there were no cardiovascular benefits found from taking 2000IU and 1gm (respectively)/day over 5.3 years. There did appear to be significant reductions in heart attacks, percutaneous coronary interventions, and total coronary heart disease in the omega-3 experimental arm. However, these differences were not enough to influence the primary outcome of total cardiovascular disease events. Of particular interest is the fact that participants who consumed less than 2 servings of fish per week experienced the greatest cardiovascular benefit. Also, past research shows that cardiovascular benefits of vitamin D blood levels level off around 25 ng/dL which is easily attainable. It is possible that patients in the vitamin d placebo arm were not at risk for lower vitamin d blood levels. Other previous research demonstrates that omega-3 fish oil can have "anti-thrombotic, hypotriglyceridemic, blood pressure lowering, and anti-inflammatory effects; impeded growth of atherosclerotic plaques; slowing of heart rate; reduced susceptibility to cardiac arrhythmias; and promotion of nitric-oxide induced endothelial relaxation." It is unfortunate that this large trial did not reflect these previous findings and it is possible that the dosage may not have been adequate to produce the results expected.

Bergamot has demonstrated repeatedly its positive impact on cholesterol. This is a citrus fruit grown in Italy and it's what is added to black tea to make Earl Grey. In one clinical trial that administered daily bergamot polyphenol extract complex 650mg, 1300mg, or placebo for 90 days, there was a dose dependent improvement in total cholesterol, LDL, HDL, triglycerides, and fasting blood glucose. This study also found significant drops in body weight and BMI. For patients who cannot tolerate statin therapy, I highly recommend a close look at bergamot supplementation.

In Traditional Chinese Medicine, Xiao Yao San (or XYS) has been used for hypertension. A recent meta analysis covering 17 trials including a total of 1460 participants looked at trials that use XYS in addition to standard western anti-hypertensive medications. Their findings showed potential benefit for lowering BP, improving depression, regulating blood lipids, and inhibiting inflammation. However, better designed studies are needed to confirm efficacy and safety.

I am excited to discuss a trial currently investigating the Chinese herb Luofengning granules for unstable angina. They are adding this therapy to current best medical practices as defined by western standards. They are hoping to find additional efficacy and a safety profile for this intervention. They will be specifically looking at major cardiac adverse events as well as biomarkers of inflammation, clotting, and heart health.

To wrap things up, I feel confident recommending some specific things for cardiovascular health. Of course, advise patients who smoke to quit. Get regular exercise and reduce stress. Excellent options that target both of these include tai chi, chigong and yoga, but patients should not feel restricted to these. I would recommend increasing fruit and vegetable intake. I highly recommend supplementing with at minimum selenium 200mcg and magnesium 300mg supplements OR a good quality multivitamin that includes both. I highly recommend bergamot 1300mg and CoQ10 200mg daily. Daily supplements of aged garlic extract 300mg and ginger 1000mg may also provide some benefit - however, caution must be taken when combined with blood-thinning medications and garlic. Although vitamin D and fish oil did not pan out in the VITAL trial, I would still recommend fish oil to patients who do not eat fish regularly and vitamin D for other health benefits. If patients are interested in TCM, there are a few options, but the data is not strong enough for me to support it without strict observation by a licensed practitioner.

Thank you for joining me today. I hope you were able to learn something about cardiovascular health. I know I did. If you know of other healthcare professionals who might benefit from this podcast, let them know where to find me! If you have any comments, concerns, or questions, feel free to email me at integratedpharmacist@gmail.com. Thanks again and we'll see you me next time on the integrated pharmacist podcast.

References:

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