Stroke Prevention: A Lifetime of Lessons — A Patient's Guide to Treating Arteries, Not Just Risk Factors

Table of Contents

• Key Points
• Why Stroke Prevention Matters
• A New Philosophy: Treating Arteries Instead of Just Risk Factors
• Personalized Blood Pressure Treatment: The Renin/Aldosterone Approach
• Lifestyle Changes: The Foundation of Artery Health
• Medical Therapies: Medications That Protect Your Arteries
• Blood Pressure in the Brain: Why Small Vessels Matter
• Real-World Success: The Argentina Experience
• What This Means for Patients
• Study Limitations
• Practical Recommendations for Patients
• Frequently Asked Questions
• Source Information

Key Points

• Treating arteries directly, rather than just risk factor numbers, is a more personalized stroke prevention approach.
• Measuring renin and aldosterone helps select the right blood pressure medication for resistant hypertension.
• Showing patients their own artery plaque can motivate lifestyle change and plaque regression is achievable.
• In an Argentine clinic network, annual cardiovascular events fell from 5.85% to 2.35% after implementing this approach.
• Lifestyle changes include Mediterranean diet, exercise, smoking cessation, and avoiding drugs like decongestants that raise blood pressure.

Why Stroke Prevention Matters

Stroke remains one of the leading causes of death and disability worldwide. Yet the startling truth is that most strokes are preventable. Dr. Spence's lifetime of research, honored with the Feinberg Award in 2020, shows that prevention is far more powerful than treatment after a stroke occurs.

The traditional approach to stroke prevention has been to identify risk factors—things like high blood pressure, high cholesterol, diabetes, and smoking—and treat each one with the appropriate medication. This "treat the numbers" strategy has saved countless lives, but it has an important gap: two people with identical blood pressure readings, identical cholesterol levels, and identical lifestyle habits can have dramatically different outcomes.

Why? Because risk factors are only part of the story. What really matters is what is happening inside the arteries themselves.

A New Philosophy: Treating Arteries Instead of Just Risk Factors

Dr. Spence's lecture introduces a powerful concept: rather than focusing exclusively on risk factor numbers, doctors should focus on the health of the arteries themselves. The approach is built on several key pillars, summarized in the supplement as "Treating arteries instead of treating risk factors."

The first and perhaps most innovative element involves patient education through imaging. The strategy recommends that all patients be shown images of their own arterial plaque (the fatty buildup inside artery walls that causes blockages). Doctors should compare the patient's plaque burden with that of healthy people of the same age and sex, describing the specific risks associated with that degree of buildup and what happens if it progresses. Crucially, they should also explain that plaque regression is possible—asking patients to take an active role in their own vascular health.

This visual feedback loop appears to be remarkably effective. Patients who see their own plaque may be far more motivated to take medications consistently, quit smoking, and adopt healthier diets than those who are simply told "your cholesterol is 240."

Personalized Blood Pressure Treatment: The Renin/Aldosterone Approach

High blood pressure (hypertension) is the single most important modifiable risk factor for stroke. Yet standard treatment often follows a "one-size-fits-all" pattern, where patients receive whatever medication happens to be on the formulary. Dr. Spence argues for a more scientific approach: physiologically individualized therapy based on measuring two key substances in the blood—renin and aldosterone.

Renin is an enzyme produced by the kidneys, while aldosterone is a hormone produced by the adrenal glands (small glands on top of the kidneys). Together, they form a system that regulates blood pressure by controlling salt and water balance in the body. When doctors measure these levels in a patient with resistant hypertension (high blood pressure that doesn't respond to standard treatment), they can identify which of three distinct conditions is driving the problem:

• Primary Aldosteronism: Renin levels are low, but aldosterone levels are high. This means the adrenal glands are producing too much aldosterone, causing the kidneys to retain too much salt and water. The primary treatment is an aldosterone antagonist such as spironolactone or eplerenone (for men, eplerenone may be preferred if spironolactone causes side effects). In rare cases, surgery to remove the adrenal gland (adrenalectomy) may be considered.
• Liddle's Syndrome and Variants / Inappropriate Aldosterone Secretion: Both renin and aldosterone levels are low. This condition is often caused by mutations affecting a sodium channel in the kidneys (the renal sodium channel). The kidneys retain salt even without aldosterone stimulation. The primary treatment is amiloride, a medication that directly blocks this sodium channel.
• Renal/Renovascular Hypertension: Both renin and aldosterone levels are high. This usually means that the kidneys themselves are not getting enough blood flow (often due to narrowing of the arteries supplying the kidneys). The kidney releases excess renin to try to raise blood pressure and improve flow. The primary treatment is an angiotensin receptor blocker (ARB) or a renin inhibitor. In rare cases, surgically reopening a narrowed kidney artery (revascularization) may help.

This classification, originally developed for treating uncontrolled hypertension in African patients (published in the American Journal of Hypertension in 2017 by Akintunde and colleagues), transforms blood pressure treatment from guesswork into precision medicine. A simple blood test can save patients months or even years of ineffective treatment.

The supplement also notes a simple but often overlooked tip: switching from non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen to sulindac, which has less effect on blood pressure control. A 1986 study in The Lancet by Wong and colleagues showed that certain pain medications can interfere with blood pressure medications—a lesson many patients never hear.

Lifestyle Changes: The Foundation of Artery Health

The second major component of "Treating Arteries" is lifestyle modification, and the supplement outlines a detailed, practical plan:

Smoking Cessation

Smoking damages the lining of arteries, accelerates plaque buildup, and dramatically increases stroke risk. The recommended approach goes beyond simple advice: it includes counseling, liberal use of nicotine replacement therapy (patches, gum, lozenges), and medications such as varenicline or bupropion—with bupropion preferred if the patient has a history of depression, since it can also address mood symptoms.

Mediterranean Diet

Patients should be counseled on the Mediterranean diet—rich in fruits, vegetables, whole grains, fish, and healthy fats like olive oil. The supplement notes that patients should receive a booklet with advice, recipes, and links to helpful websites, with reinforcement at every follow-up visit. One-time advice is rarely enough; repetition is essential.

Weight Management and Exercise

Obesity is addressed with counseling on caloric restriction, referral to a dietician, and—for refractory patients with severe obesity plus diabetes or insulin resistance—referral for bariatric surgery. Exercise recommendations are for moderate activity at least 30 minutes a day, with advice tailored to each patient's disabilities. For someone with limited mobility, even chair-based exercises can help.

Blood Pressure-Friendly Habits

Simple dietary changes can have a big impact on blood pressure: reducing salt intake, limiting alcohol consumption, avoiding licorice (which contains a compound that raises blood pressure), and avoiding decongestants, which can also elevate blood pressure.

Medical Therapies: Medications That Protect Your Arteries

The medical therapy component of "Treating Arteries" is just as detailed as the lifestyle component, with strategies designed to halt plaque progression and ideally achieve plaque regression:

• Lipid lowering (statins): Treatment begins with statins, with doses increased according to how the patient's plaque responds on imaging. If plaque continues to progress, the dose is raised to the highest tolerated level. Coenzyme Q10 (CoQ10) is used to minimize muscle pain (myopathic symptoms) that can cause patients to stop taking their statins. If statins alone aren't enough, ezetimibe is added. For patients with low HDL (good cholesterol) and high triglycerides, fibrates are added. If accessible, newer PCSK9 inhibitor medications—which dramatically lower cholesterol—are recommended.
• Antiplatelet therapy: Low-dose aspirin is used to prevent blood clots, with the addition of clopidogrel in patients with severe narrowing (stenosis) of the arteries or other high-risk indicators.
• Anticoagulation: For patients with atrial fibrillation (an irregular heart rhythm that increases stroke risk fivefold) or other cardiac sources of stroke, blood thinners (anticoagulants) are essential.
• Insulin resistance and prediabetes: The medication pioglitazone is recommended, based on a post-hoc analysis of the IRIS randomized clinical trial published in JAMA Neurology in 2019 by Spence and colleagues. This study showed benefits of pioglitazone in patients who had experienced a stroke and were living with prediabetes. Lifestyle reinforcement remains crucial.
• Diabetes: Patients with full diabetes are referred to a diabetes clinic, with ongoing reinforcement of lifestyle changes.

Blood Pressure in the Brain: Why Small Vessels Matter

The supplement also addresses a lesser-known but critical mechanism in stroke: blood pressure gradients within the brain's small arteries. Using computer simulations (published by Blanco, Muller, and Spence in Stroke and Vascular Neurology in 2017), researchers compared blood pressure patterns in people with normal blood pressure (normotensive) and those with hypertension.

The simulations measured pulsatile pressure—the wave of pressure that travels through the arteries with each heartbeat—at various points in the brain's blood supply, including:

• Medium-sized arteries: the internal carotid artery (ICA), middle cerebral artery (MCA), posterior cerebral artery (PCA), and basilar artery (BA)
• Small-sized arteries: the lenticulostriate arteries (LsA), distal medial striate arteries (DMSA), prefrontal arteries (PfA), and posterior parietal branches (PPB)

The findings help explain why high blood pressure is so damaging to the brain's small vessels. The pressure waves that reach these delicate arteries are influenced by the stiffness of larger arteries above them. In hypertension, the larger arteries lose their cushioning effect, sending higher-pressure pulses deep into the brain where they can damage the small vessel walls. This is thought to be a key mechanism behind cerebral small vessel disease, which is a major cause of both strokes and dementia.

Real-World Success: The Argentina Experience

Perhaps the most encouraging evidence in the supplement comes from an unpublished real-world implementation of the "Treating Arteries" approach. Beginning in 2012, Blossom DMO—a healthcare organization operating seven large health maintenance organizations across Argentina—implemented the "Treating Arteries" protocol in its vascular prevention clinics.

The results, presented by Dr. Luis Armando in August 2016 at a seminar at the University of Oxford, are striking:

• The number of participants aged over 65 increased from 1,675 in 2011 to 2,000 in 2015
• The annual rate of cardiovascular events dropped from 5.85% to 2.35% over that period

Cardiovascular events in the study included a composite of Major Coronary Events (heart attacks with or without ST-segment elevation and unstable angina), Stroke, Coronary Revascularization (procedures like stents or bypass surgery), and Peripheral Vascular Events (vascular amputation, peripheral revascularization, or new-onset claudication—leg pain caused by blocked arteries).

This 60% reduction in cardiovascular event rates—achieved in a real-world setting across multiple clinics, not in a controlled research environment—suggests that the "Treating Arteries" approach is not just theoretically sound but practical and effective on a large scale.

What This Means for Patients

For patients living with high blood pressure, high cholesterol, diabetes, or a history of stroke, these lessons carry several profound messages.

First, you are not a number. Two patients with the same blood pressure reading may need completely different medications. If your blood pressure hasn't responded to treatment, ask your doctor about renin and aldosterone testing. This simple blood test could identify the underlying cause and lead to far more effective treatment.

Second, seeing is believing. If your doctor offers to show you images of your own arteries, take a good look. Understanding your personal plaque burden can be one of the most powerful motivators for lifestyle change. And remember: plaque regression—not just slowing its growth—is achievable.

Third, the drugstore matters. Over-the-counter medications you use for pain or colds could be raising your blood pressure and interfering with your prescription medications. If you have high blood pressure, talk to your doctor about which pain relievers are safe for you.

Fourth, statins are just the beginning. Modern cholesterol treatment is personalized and increasingly powerful. If one medication isn't enough, there are now multiple options—ezetimibe, fibrates, PCSK9 inhibitors—that can be added to get your cholesterol to target and stop plaque in its tracks.

Study Limitations

It is important to understand the limitations of the evidence presented in this supplement. The lecture is a synthesis of Dr. Spence's career work, drawing on multiple clinical trials and observational data rather than a single new trial. The renin/aldosterone phenotyping approach was studied in an African population and may not apply identically to all ethnic groups, though the underlying physiology suggests broad relevance.

The Argentina data, while impressive, comes from an observational implementation without a comparison group or randomized controls. The decline in cardiovascular events could theoretically reflect broader improvements in healthcare during the same period, though the magnitude of change suggests the program played a major role. Additionally, detailed information about how consistently the protocol was applied at each of the seven organizations is not available in the supplement.

The blood pressure gradient research relies on computer simulations rather than direct measurements in humans, though the models are based on validated physiological parameters. Finally, some of the specific recommendations—such as the use of CoQ10 to reduce statin-related muscle symptoms—reflect clinical experience and expert opinion that may not be supported by large randomized trials.

Practical Recommendations for Patients

Based on the lessons from Dr. Spence's lecture, here are practical steps patients can discuss with their healthcare providers:

1. Ask about renin/aldosterone testing if your blood pressure remains elevated (above 130/80 mmHg) despite taking two or more blood pressure medications.
2. Request vascular imaging (such as carotid ultrasound) to assess plaque burden, and ask to see and discuss your results during the visit. If feasible, ask about follow-up imaging to track plaque progression or regression over time.
3. Review your medication list, including over-the-counter drugs and supplements, with a pharmacist or physician at least once a year. Pay special attention to pain relievers and decongestants.
4. Be persistent with statins. If you experience muscle pain, don't simply stop your statin—ask your doctor about CoQ10 supplementation or switching to a different statin. Many patients can find a statin regimen they can tolerate.
5. Eat Mediterranean-style: more vegetables, fruits, beans, nuts, fish, and olive oil; less red meat, processed food, and refined sugar. Ask for printed resources, and revisit your diet goals at each appointment.
6. Move for at least 30 minutes daily at moderate intensity—a brisk walk, swimming, or cycling. If you have physical limitations, ask your doctor for exercises tailored to your situation.
7. If you smoke, treat cessation like a medical emergency. Ask for nicotine replacement therapy and medications (varenicline or bupropion) at your next appointment. Every year of continued smoking significantly increases stroke risk.
8. Know your heart rhythm. If you have atrial fibrillation (even the intermittent kind), anticoagulation therapy can reduce your stroke risk by nearly two-thirds. Ask your doctor if you should be screened.
9. If you have prediabetes (a condition affecting over 80 million Americans), ask your doctor whether pioglitazone might be appropriate for you, particularly if you have already experienced a transient ischemic attack (TIA or "mini-stroke") or stroke.

The lessons from Dr. Spence's lifetime of work are clear: stroke prevention is most effective when it is personalized, proactive, and focused on the arteries themselves. While the science is sophisticated, the message for patients is beautifully simple: knowledge is power. Understand your own risk, participate actively in your treatment decisions, and never stop working to improve the health of your arteries.

Frequently Asked Questions

Why do two people with the same blood pressure and cholesterol have different stroke outcomes?

Risk factor numbers are only part of the story. What really matters is what is happening inside the arteries themselves. The same blood pressure or cholesterol reading can reflect different arterial health in different people. Doctors can now focus on treating the arteries directly, using imaging to see plaque buildup and personalized treatments based on each patient's physiology.

What is the renin/aldosterone blood test for high blood pressure?

It measures two substances that regulate salt and water balance in the body. Based on the levels, doctors can identify which of three conditions is driving resistant hypertension: primary aldosteronism, Liddle syndrome or variants, or renal/renovascular hypertension. The test helps choose the most appropriate medication, such as spironolactone, amiloride, or an ARB, instead of using a one-size-fits-all approach.

How can I see my own artery plaque and why does it help?

Doctors can show you images of your arterial plaque from tests like carotid ultrasound, comparing it to healthy people of your age and sex. Seeing your own plaque buildup can motivate you to take medications consistently, quit smoking, and adopt healthier habits. The article says plaque regression is possible, and patients who see their own plaque may be more motivated to make changes.

What lifestyle changes does the treating arteries approach recommend?

It recommends smoking cessation with nicotine replacement or medications like varenicline or bupropion, a Mediterranean diet rich in fruits, vegetables, fish and olive oil, weight management and exercise for at least 30 minutes daily. It also advises reducing salt and alcohol, avoiding licorice and decongestants, and getting blood pressure-friendly habits. Repetition and reinforcement at every follow-up visit are considered essential.

What medications are used to protect arteries and stop plaque progression?

Statins are the starting point, with the dose increased if plaque progresses. CoQ10 may help with statin muscle pain. Ezetimibe and fibrates can be added, and PCSK9 inhibitors if accessible. Low-dose aspirin is used, plus clopidogrel for severe narrowing. Anticoagulants are given for atrial fibrillation. Pioglitazone is recommended for insulin resistance or prediabetes after a stroke.

Does the treating arteries approach really reduce heart attacks and strokes?

In a real-world implementation at seven health maintenance organizations in Argentina, starting in 2012, the annual rate of cardiovascular events dropped from 5.85% to 2.35% by 2015. This was an observational study without a comparison group, so the reduction might partly reflect broader healthcare improvements, but the magnitude suggests the program played a major role.

What should I ask my doctor about stroke prevention based on this article?

Ask about renin/aldosterone testing if your blood pressure stays above 130/80 despite two or more medications. Request vascular imaging to see your plaque burden and ask about follow-up imaging. Review all medications, including over-the-counter pain relievers and decongestants, with your pharmacist. If you smoke, ask about cessation aids. If you have prediabetes and had a TIA or stroke, ask about pioglitazone.

My blood pressure stays high on two medications. Should I get a second opinion about renin and aldosterone testing before changing my stroke prevention plan?

Yes, a second opinion can help if your blood pressure remains above 130/80 despite two or more medications. The renin/aldosterone blood test identifies which of three conditions drives resistant hypertension, guiding specific treatment like spironolactone, amiloride, or an ARB. This personalized approach, part of treating arteries rather than just risk factors, was linked to a 60% reduction in cardiovascular events in a real-world Argentine clinic network. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original Article: "Stroke Prevention: a Lifetime of Lessons" — The Feinberg Award Lecture 2020, supplemental material.

Author: J. David Spence, M.D.

Publication Details: This supplement accompanies the Feinberg Award Lecture presented in 2020. It includes material reproduced by permission from the American Journal of Hypertension (Akintunde et al., 2017), JAMA Neurology (Yang et al., 2015; Spence et al., 2019), The Lancet (Wong et al., 1986), and Stroke and Vascular Neurology (Blanco et al., 2017). The Argentina data was previously unpublished and reproduced by permission of Dr. Luis Armando, Blossom DMO, with acknowledgment of Dr. Hernan Perez, Dr. Hugo Villafañe, and Dr. Nestor Garcia.

Note: This patient-friendly article is based on peer-reviewed research and lecture materials. It is intended for educational purposes and does not constitute medical advice. Always consult your healthcare provider before making changes to your medications or treatment plan.