A Systematic Approach to Treating and Preventing CVD
A Systematic Approach to Treating and Preventing CVD
by Krista Russ
The CVD Burden: A Product of Misinformation
Despite tremendous gains in diagnosis and treatment, cardiovascular disease (CVD) remains a serious clinical problem and one of the largest threats to public health. As physicians, our approaches to treating cardiovascular disease and its related ailments like stroke are almost entirely centered around symptom management without addressing the underlying causes or worse, based on outdated, unsubstantiated information that continues to persist in the medical community.
Why isn’t our approach working? The answer to that is complicated and could fill entire books, but the simple answer is that we aren’t adequately addressing CVD’s underlying pathology. For example, cholesterol has been attacked for causing heart disease for decades thanks to unsupported and cherry-picked research from Ancel Keys’ seven countries study that laid the foundation for a low fat, low cholesterol diet. His study ignored data that an increase in sugar consumption (as well as smoking) was far more correlated with coronary heart disease deaths than saturated fat was (per Men’s Health ).
As soon as his recommendations were applied nationally, obesity rates skyrocketed followed by an increase in type two diabetes, one of the strongest risk factors for the very heart disease he was trying to prevent. This was despite the fact that Keys himself later admitted a decade after the study’s release “I’ve come to think that cholesterol is not as important as we used to think it was.” to the New York Times, but the ship had already sailed (per Men’s Health ). There was too much money to be made off the fear of fat and cholesterol.
Saturated Fat and Cholesterol are Not The Villains
Only recently has the American Heart Association (AHA) quietly dismissed the recommendation to restrict dietary cholesterol, citing a lack of scientific support that dietary cholesterol raises serum cholesterol levels (per the journal Circulation ). In fact, groundbreaking 2020  and 2021 research  out of the prestigious journal BMJ Evidence-Based Medicine and the Journal of The American College of Cardiology supports there is a much stronger link with processed carbohydrates as it relates to cholesterol and triglycerides than there is with either saturated fat or dietary cholesterol, citing no evidence to support the claim that a diet low in either saturated fat or cholesterol reduces the risk for heart disease. And while saturated fat does increase cholesterol in observational studies, outcome based studies do not show an increase in CVD or strokes as a result. But how could that be so? Haven’t we always been told saturated fat and cholesterol causes heart attacks?
Well it turns out there are different types of LDL cholesterol: pattern A and pattern B. Pattern A is large and buoyant, making it far less likely to adhere to blood vessel walls, but Pattern B is small and dense and more likely to squeeze through the gaps between endothelial cells, gaining access to adhere to artery walls. Pattern B cholesterol is associated with a 3-fold increased risk for heart attack and an increased risk for atherosclerosis (per The AHA journals ).
Saturated fat raises LDL, but it usually only raises the innocuous pattern A cholesterol; not pattern B (per 2021 research ). And dietary cholesterol doesn’t raise cholesterol much at all (per the journal Circulation ). And while the LDL pattern type is primarily inherited, we know that lifestyle influences this distribution too, such as fructose (sugar) and processed carbohydrate consumption which increases pattern B cholesterol (per a 2013 study  out of the BMJ). In simpler words, not everyone with elevated LDL is at an increased risk for heart disease.
Furthermore, cholesterol is used for repairing the arteries when they become damaged. It is an innocent bystander that is blamed and blamed again for causing CVD and heart attacks, but only once cholesterol has become oxidized, inducing inflammation, is CVD actually a concern–something that happens much more readily with our high sugar, seed-oil (omega 6)-rich diet.
High Blood Pressure: Is it all salt?
And the link between insulin resistance or I.R may indeed have a stronger link to high blood pressure than salt (per a 2020 study ). According to the journal, “Insulin resistance contributes to increase BP through several mechanisms, among which are the enhanced tissue angiotensin II (AngII) and aldosterone activities, the increased sympathetic nervous system activity, and oxidative stress.”
We also know that sedentary lifestyle and obesity contributes to high blood pressure and both are strongly associated with insulin resistance, likely explaining at least part of why this association exists.
Ironically, a low salt diet may even precipitate insulin resistance by increasing aldosterone (per a 2011 study ), and insulin resistance often leads to type two diabetes, which has been shown to increase the risk for fatal heart disease or stroke in 90% of patients within the next decade (per a 2021  study). So a low-salt diet may not be right for everyone after all.
But even with new information, protocols are often very slow to change in the medical community. Old recommendations stick, even when they are weakly supported or not supported at all. So, what heart disease risk factors have been proven with factual research?
Heart Disease Risk Factors
- Hypertension (often caused by I.R, obesity, or sometimes salt-sensitivity)
- High triglycerides (caused by I.R)
- Elevated LDL, pattern B cholesterol (associated with I.R)
- Low HDL cholesterol
- Insulin resistance and diabetes
- Abdominal obesity/high visceral fat
- Sedentary lifestyle
- Prolonged sitting
- Excessive alcohol
- Cigarettes and tobacco
- Processed and ultra-processed foods (low fiber, high sugar, white flour, high glycemic diet)
- Family history
How Do We Target Root Causes?
In addition to addressing these well-supported risk factors for CVD with your patients with nutrition and physical activity, we also know there are several, evidence-supported supplements and prescriptions that offer further cardiovascular support for both the prevention and treatment of CVD. We will explore the exciting research regarding these avenues next.
You probably know that oxytocin is an important hormone involved in things like labor, milk letdown, and sexual response. In the medical setting, you likely recognize oxytocin as the hormone used to induce labor when given synthetically as Pitocin, but you probably didn’t know it could help your CVD patients too. A 2020 paper  out of the journal Frontiers in Psychology highlighted many of oxytocin’s CVD-related documented benefits, such as:
- Beneficial effects on infarct size
- Increases recovery of the ischemic heart
- Improves cardiac work
- Reduces apoptosis and inflammation in cardiac tissue
- Increases scar vascularization
- Protects cells through the production of cGMP and nitric oxide synthesis
When cardiac patients are treated with oxytocin, there is a reduction in inflammatory cytokines and infiltration by immune cells, reducing cellular death. In addition to controlling inflammation, oxytocin fosters stem cell development including cardiomyocytes, endothelial, and smooth muscle cells and induces angiogenesis which may assist in heart attack recovery.
The paper also states, “In cardiac and cellular models of ischemia and reperfusion, acute administration of oxytocin at the onset of reperfusion enhances cardiomyocyte viability and function…”
Oxytocin also has favorable effects on blood pressure. Subcutaneous injections decrease blood pressure through peripheral activation on the cardiovascular system and kidneys. Blood pressure is also decreased by oxytocin’s effects on the autonomic nervous system.
Nitric Oxide (NO) Support
Nitric Oxide is an important vasodilator that increases blood flow (per Healthline ). This has important implications for several aspects of health because without adequate blood flow, nutrients and oxygen cannot reach their respective destinations efficiently, so it’s no wonder that low nitric oxide is associated with all sorts of health effects such as diabetes, erectile dysfunction, and heart disease. Because of its role as a vasodilator, it also decreases blood pressure, an important cardiovascular risk factor. But what else does the literature show about NO and the heart?
According to a 2018 study  out of Case Western Reserve University School of Medicine, Nitric Oxide may determine the efficiency of heart medications. This is because many of the receptors that heart disease drugs target simply don’t work without nitric oxide; thus, ample nitric oxide could improve the efficacy of common heart drugs. NO does this by activating G protein-coupled receptors (GPCRs).
The same study showed a lack of NO increases the harmful side effects of heart drugs. This is because a lack of NO amps up the heart drug’s ability to activate the type of receptor associated with side effects called arrestins. Adequate NO ensures that heart drugs activate the receptors we want (those that provide heart benefits–the GPCRs) and don’t activate the ones that produce harmful side effects (the arrestins).
The study also showed that a lack of NO likely underlies heart failure, boosting efforts to replace it. To prove this, the researchers genetically engineered mice to be unable to attach nitric oxide to the arrestin pathway only. Jonathan Stamler, MD, senior author of the study explains, “The mice had classic features of heart failure. Without nitric oxide signaling, they could not increase heart rate or pump function.”
While patients can’t supplement with NO directly, they can supplement with NO precursors. Nitrate-rich foods like beets, kale, and celery can help. Nitrates found in beetroot powder supplements, as well as the amino acids L-citrulline and L-arginine have been shown to boost NO levels as well. Lastly, the hormones estradiol and testosterone can raise NO levels and may be an option for patients considering hormone replacement therapy.
CoQ10 has been in the spotlight for heart health lately and for good reason. This top-selling supplement may reduce recurring heart attacks and improve the prognosis in heart failure patients (per Cleveland Heart Lab ). It even lowers blood pressure and reduces some of the negative side effects of statins.
You might recall from your biochem days that CoQ10 is an important coenzyme necessary for metabolic reactions in human cells. As a part of the electron transport chain, it fosters aerobic cellular respiration in the mitochondria for the purposes of generating ATP (per the text Bioscience, Biotechnology, and Biochemistry ). You might even recall that in addition to its role as an important cofactor for energy production, it is an electron donor (antioxidant).
Although the body makes CoQ10, studies show that additional supplementation can provide therapeutic benefits, especially for heart health such as these (per Cleveland Heart Lab ):
- Reduces repeat heart attacks. In a randomized clinical trial , patients who received CoQ10 after a heart attack had fewer subsequent cardiac events over the next year compared to the control group (24.6 percent versus 45 percent).
- CoQ10 supplements can significantly increase HDL-C and ApoA1 levels and may help reduce risk for CVD, even for statin patients.
- CoQ10 supplementation lowers levels of inflammatory biomarkers such as high-sensitivity C-reactive protein, an important CVD risk factor.
- Low CoQ10 levels are associated with greater tissue damage to the heart and brain following a heart attack or stroke respectively.
- Up to a quarter of patients quit statin treatment within six months due to side effects. A 2014 randomized clinical study  found that 75 percent of statin users with muscle symptoms reported pain reduction after taking CoQ10 twice a day for a month.
- Statins can decrease blood levels of CoQ10, which is another reason why supplementation is so important.
Resveratrol (RES) is a polyphenol found in foods like grapes, red wine, and berries. It has recently come into the spotlight for its heart-related benefits, with many peer-reviewed journals supporting its role in heart health such as:
Resveratrol and Cardiovascular Diseases  –per the journal Nutrients
- RES upregulates endothelial nitric oxide synthase.
- Scavenges cell-damaging peroxyl particles which can reduce lipid peroxidation. Lipid oxidation underlies plaque buildup, so preventing it has direct benefits for CVD prevention.
- Increases NO availability in diabetes, which is reduced and improves their endothelial function.
- Some preclinical studies show that RES can decrease plasma triglyceride and LDL-cholesterol levels, and increase HDL-cholesterol, potentially benefiting the early stages of atherosclerosis.
- Decreases reactive oxygen species and inflammation, which are essential components to the CVD disease process.
- Potential to regenerate tissue in infarcted areas following ischemia.
The Effects of Resveratrol in Patients with Cardiovascular Disease and Heart Failure: A Narrative Review –per the International Journal of Molecular Sciences
According to the review, “Atherosclerosis is often seen as a chronic low-grade inflammatory condition with a complex pathogenesis involving endothelial dysfunction, lipoprotein build up and oxidation, pro-inflammatory cytokines, and various other factors. Atherosclerosis is also the main cause of coronary artery disease (CAD), which is the most common etiology of patients with HF in developed nations.”
Many of RES’s effects target the very features that shape the development of atherosclerosis and CAD such as:
- Decreases arterial stiffness in the endothelium
- Reduces systolic blood pressure in a dose-dependent manner
- Downregulates inflammatory pathways and cytokines
- Reduces leukocyte adhesion
- Decreases total, LDL-C, and triglycerides
- Reduces fasting glucose and insulin glycated hemoglobin
Alpha Lipoic Acid (ALA)
Similar to CoQ10, Alpha lipoic acid (ALA) is an important antioxidant abundant in our cells that has the potential to benefit several health conditions with additional supplementation. Most of the research supporting ALA’s ability to improve cardiovascular health are due to its indirect effects on the heart by improving diabetes, which you already know is one of the major risk factors for cardiovascular disease. ALA also has some direct effects on the heart itself such as protecting against hypertension by reducing inflammatory cytokines and increasing the synthesis of NO, amplifying its anti-hypertensive effects (per a 2015 paper ).
It’s effects on diabetes which indirectly improve cardiovascular health include (via Healthline ):
- Lowers blood sugar in humans and animals. In one study , it lowered blood sugar levels a whopping 64 percent.
- May reduce insulin resistance and hemoglobin A1C levels
- Reducing damage to nerves and diabetic neuropathy symptoms.
It also improves cardiovascular health by reducing several markers of inflammation. For example (via Healthline ):
- In a review of 11 studies, alpha-lipoic acid significantly reduced levels of C-reactive protein (CRP) in adults with high CRP levels (per a 2018 meta-analysis ).
- In test-tube studies, alpha-lipoic acid reduced other markers of inflammation, such as NF-kB, ICAM-1, VCAM-1, MMP-2, MMP-9, and IL-6 (per multiple peer-reviewed studies: study one , study two , study three , study four ).
Fish oil is rich in the DHA and EPA omega threes which are precursors to anti-inflammatory prostaglandins. This and the ability of omega threes to thin the blood is responsible for most of its cardiovascular benefits.
The American Heart Association (AHA) has recommended omega threes from fish and fish oil for over two decades because strong research indicates it reduces the risk for cardiac events like heart attacks and strokes in people living with cardiovascular disease (per Harvard Health ). Here is some of the evidence from peer-reviewed research:
- A prescription version of concentrated EPA omega threes called Vascepa showed marked benefit in the Reduce It Trial  out of the prestigious New England Journal of Medicine. In this study, over 8,000 participants with high triglycerides were split into two groups. Half were given two grams of Vascepa twice per day while the other half were given a placebo pill. The Vascepa group not only saw significant reductions in triglycerides over the placebo but a reduced number of heart attacks, strokes, heart stent procedures, and deaths.
- In late 2020, the FDA approved the use of Vascepa for reducing the risk of cardiovascular events in patients living with or at high risk for CVD. This is groundbreaking for a medication that is arguably more like a supplement than a drug.
- A 2019 meta-analysis  out of the Journal of the American Heart Association reviewed data from thirteen randomized controlled trials on nearly 127,477 people concluded that omega three supplementation lowers the risk for both heart attacks and deaths in people with coronary heart disease.
Omega Three Considerations:
While these findings are exciting and certainly provide motivation to use omega threes in your practice, there are important considerations that determine omega three effectiveness. For example, certain combinations of omega three supplements may provide little or no benefit. And the balance of omega three to omega six in the overall diet can also determine the therapeutic benefit obtained. Fortunately, we will discuss these important considerations and more in our upcoming Heart Health Webinar.
The sex hormone estradiol is widely known for its cardioprotective properties. From reducing LDL cholesterol, to raising HDL, estradiol is an extremely important hormone. In fact, it is widely known that cardiovascular events tend to increase in menopause as a result of declining estradiol levels. Even men need estradiol for bone, brain, and cardiovascular health.
Unfortunately, the medical field has largely shunned hormone replacement therapy because of ill health effects demonstrated with equine estrogen and synthetic progesterone, better known as progestin. The widely infamous Women’s Health Initiative (WHI) scared patients and providers alike when it came to using hormone therapy because this randomized controlled primary prevention trial showed an increased incidence in ailments like heart disease, strokes, breast cancer, and blood clots (per Jama ).
In reality, all of these health effects were only demonstrated with synthetic hormones; not bioidentical ones, which mirrors what the human body makes. Generous research supports the safety and efficacy of bioidentical hormones. For example, a 2008 article  out of the journal menopause management demonstrated that estrogen therapy confers several cardioprotective benefits superior to other therapies and is very low risk. For instance, estrogen therapy reduces coronary calcium, which has proven to reduce the risk for atherosclerosis in contrast to lipid lowering drugs.
Upon analyzing data from the WHI trial, the article concluded that estrogen therapy substantially reduces total mortality and CHD occurrence in women who begin hormone replacement before age 60. But how much was it reduced? An analysis of 23 randomized controlled trials with nearly 40,000 women showed an astounding 32 percent reduction in risk of CHD in women less than 60 years of age (or less than ten years since the commencement of menopause) and a nearly 40 percent reduction in total mortality.
Furthermore, the risks associated with estrogen therapy were demonstrated to be small in comparison to the overwhelming benefit with a frequency of less than one event per 1,000 women treated with HRT, which is considered “rare” by World Health Organization criteria.
A 2005 clinical trial  analyzed how estrogen therapy influences the progression of subclinical atherosclerosis by determining the degree to which changes in lipids and carbohydrate metabolism markers induced by estrogen therapy influence the progression of carotid artery intima-medial thickness (IMT) in postmenopausal women. 222 postmenopausal women without evidence of CVD were treated with 17-beta estradiol (not synthetic estrogen) and had their carotid artery IMT’s measured at baseline using ultrasound and again every 6 months of the trial. Not only did several metabolic markers improve (fasting glucose and insulin, A1C, HDL and LDL, insulin sensitivity, etc.) but women randomized to estradiol saw positive changes in their carotid IMT thickness as a result of the beneficial lipid changes, explaining some of the mechanism of action behind estradiol’s beneficial heart effects.
Estradiol has also been shown to increase nitric oxide in the cerebrovascular endothelium, leading to vasodilation and inhibition of platelet aggregation, which could protect against stroke (per The AHA journals ).
We will introduce the value of adding bioidentical hormone replacement therapy with regards to estradiol in more detail at our upcoming webinar on heart health, including the best form to use. This information is important because only certain forms of estradiol produce cardiovascular benefits. We also discuss the benefits, safety, dosage, and efficacy of estradiol and other bioidentical hormone therapies in greater depth in our Bioidentical Hormone Replacement Therapy (BHRT) Training Workshop, so be sure to register.
In order for your patients to gain cardiovascular benefits, you must know how to prescribe these supplements and hormones. You must understand which circumstances to use them for and what doses align best with those circumstances. Fortunately, we will describe what the literature shows on dosing for optimal health in our upcoming Heart Health Webinar.
The insight you will gain here is crucial for making the best use of these tools in your practice. You will also learn more details like what forms are best for ideal absorption. As you know, certain drug forms are better absorbed than others for the same drug, and the same is true of supplements and hormones. This insight is indispensable for helping your patients achieve optimal heart health.
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