Risk Factors for Stroke
Age, gender, race, ethnicity, and genetics have all been identified as non-modifiable risk factors for stroke, with age being the most important (Sacco 1997; Khaw 2006; Francis 2007).
- Age. The stroke rate more than doubles in men and women for each 10 years over age 65.
- Gender. Stroke rates are higher in men than women, but more women die of stroke each year.
- Race & ethnicity. Stroke rates vary extensively among different racial groups. For example, African-Americans are statistically twice as likely to die from strokes as whites. Stroke incidence has risen sharply in Chinese and Japanese populations. Specifically, stroke leads heart disease as a cause of death in Japan.
- Genetics/ hereditary factors. The Framingham Offspring Study demonstrated that family history of stroke is a strong predictor of future stroke risk.
Modifiable stroke risk factors include:
High Blood Pressure
Hypertension, the strongest risk factor for cardiovascular disease worldwide, is associated with about half of ischemic strokes (Kokubo 2012). Also, estimates indicate that 17 to 28% of hemorrhagic strokes among people with high blood pressure could be prevented with blood-pressure lowering treatment (Woo 2004). About 1 in 3 American adults have high blood pressure (AHA 2012b). According to the Cardiovascular Lifetime Risk Pooling Project, men with hypertension throughout middle age have the highest lifetime risk for stroke (Allen 2012).
Blood pressure is measured as systolic and diastolic pressure. Systolic pressure is measured when blood is expelled from the heart as it contracts. Diastolic pressure is measured between contractions. Systolic is the “top” or “first” number, diastolic is the “bottom” or “second”. For most aging individuals, Life Extension recommends an optimal blood pressure target of 115/75 mmHg.
Many clinicians have not adequately addressed the problem of hypertension because of the lax conventional definition of "acceptable" blood pressure. In 2012, it was shown that men and women with consistent blood pressure below 120/80 mmHg had the lowest lifetime risk of stroke and cerebrovascular disease (Allen 2012). It has also been reported that each 20/10 mmHg increase over 115/75 mmHg doubles the risk of several vascular complications, including heart attack, heart failure, stroke, and kidney disease (Franco 2004). Unfortunately, studies have shown that some medical professionals are unlikely to aggressively treat hypertension until blood pressure levels reach 160/90 mmHg (Hyman 2002).
Elevated blood pressure can contribute significantly to endothelial dysfunction> - impairment of normal function of the endothelium, the delicate cellular lining of the inside of blood vessels (Del Turco 2012; Davel 2011). High blood pressure can alter the endothelium and decrease the motility of the arteries and stiffen the arterial wall (Felmeden 2003). When arteries become stiff, they no longer contract and dilate normally, placing stress on the heart (NIH 2011). High blood pressure also contributes to atherosclerosis and blood clot formation. Refer to the Blood Pressure Management Protocol for more information.
Elevated Homocysteine Homocysteine is an amino acid derivative that can damage blood vessels. High homocysteine levels have been associated with an increased risk of stroke recurrence (1.74-fold) and all-cause death (1.75-fold) (Zhang 2010). Homocysteine disrupts endothelial tissue and inhibits the growth of new endothelial cells, which contributes to atherosclerotic plaque formation. Homocysteine can also disrupt the function of brain cells and compromise their survival (Manolescu 2010).
Life Extension recommends an optimal homocysteine level of less than 8 µmol/L. One comprehensive review showed that every 2.5 µmol/L increase above this level is associated with about a 20% increase in stroke risk (Homocysteine Studies Collaboration 2002).
C - reactive protein (hsCRP) C-reactive protein (CRP) is a protein in the blood that correlates with the level of systemic inflammation (Huang 2012b). Elevated CRP measured by a high-sensitivity C-reactive protein blood test is associated with incidence and severity of stroke. C-reactive protein is synthesized by liver cells, and its rate of synthesis is regulated by pro-inflammatory proteins such as interleukin-6 and interleukin-1. While in healthy humans the level of hsCRP is relatively low, it becomes elevated with inflammation, infection, and tissue damage (Casas 2008).
The Cardiovascular Health Study and Emerging Risk Factors Collaboration, both performed a decade ago, found that elevated hsCRP is a risk factor for stroke and can predict stroke outcome. In 2008, the JUPITER trial, which involved 17 802 healthy subjects with hsCRP levels greater than or equal to 2.0 mg/L, found that cholesterol-lowering statin drugs significantly reduced stroke incidence. This may be due in part to an anti-inflammatory effect of statins (Everett 2010; Elkind 2010). In a group of Chinese patients, high levels of C-reactive protein (above 3 mg/L) 15 days before ischemic stroke onset independently predicted death within 3 months (Huang 2012b). Another study involving 467 subjects found that elevated (highest vs. lowest quartile) hsCRP was associated with a more than 4-fold increase in risk of death over 4-years of follow-up after first ischemic stroke (Elkind 2010).
The plasma level of hsCRP is a powerful predictor of endothelial dysfunction, stroke, and vascular death in individuals without known cardiovascular disease. Levels of hsCRP higher than 1.5 mg/L are associated with an increased risk of death after ischemic stroke (Di Napoli 2001). Elevated levels of hsCRP may also be a predictor of secondary cerebrovascular events after an initial stroke (Di Napoli 2005). Life Extension recommends an optimal blood level for hsCRP of less than 0.55 mg/L in men and less than 1.0 mg/L in women.
Fibrinogen is a component of blood involved in the clotting/coagulation process. It is converted through enzymatic reactions into the protein fibrin, which binds with other proteins to form a clot. High levels of fibrinogen are associated with cerebrovascular disease, even when other known risk factors such as cholesterol are normal (Kaslow 2011). A study in a Taiwanese population indicated that excess fibrinogen is a major independent predictor of future stroke risk (Chuang 2009). Life Extension recommends an optimal fibrinogen blood level of 295 - 369 mg/dL.
High LDL Cholesterol
Cholesterol, found in all the body's cells, is important for normal cellular function. Cholesterol is carried to and from cells by lipoproteins (high-density lipoprotein [HDL] and low-density lipoprotein [LDL]). LDL (“bad cholesterol”) can contribute to buildup of plaque in arterial walls (AHA 2012d). Studies indicate that high levels of LDL and triglycerides are associated with increased risk of stroke and transient ischemic attack. Statins, drugs that lower LDL cholesterol, reduce stroke risk by as much as 18% and reduce stroke-related deaths by 13% (Rothwell 2011). High levels of HDL (“good cholesterol”) are associated with reduced risk of stroke or cerebrovascular disease (Sacco 2001).
Cholesterol-lowering statin drugs not only reduce the incidence of first stroke, but also reduce chances of having a second, often more debilitating stroke. Statin use is recommended in those who have already experienced a stroke or transient ischemic attack and have an LDL cholesterol level of 100 mg/dL or higher, with the aim of reaching an optimal level of 70 mg/dL (Davis 2012). Life Extension recommends optimal HDL levels over 50-60 mg/dL. Refer to the Cholesterol Management protocol for more information.
Insulin Resistance / Glucose Intolerance
Insulin resistance is a metabolic disorder characterized by reduced sensitivity to the hormone insulin, which regulates blood sugar levels. Insulin signals cells to uptake glucose from the blood. In conditions where insulin levels are low or insulin does not function properly, such as diabetes, blood sugar levels are abnormal. Insulin resistance occurs when insulin levels are normal but its ability to regulate blood sugar is impaired. This results in elevated blood sugar. The insulin-resistant state is associated with hypertension, endothelial dysfunction, abnormal fibrinogen levels, and increased concentrations of LDL particles in the bloodstream (Furie 2008).
In a multiethnic, population-based study of non-diabetic individuals, insulin resistance was associated with a 2.8-fold increased occurrence of a first ischemic stroke (Rundek 2010). This result corroborates previous observational findings that insulin resistance is an independent risk factor for stroke. In the Helsinki Policeman Study, which involved 970 healthy men aged 34 to 64, the rate of stroke incidence was 2-fold higher in diabetes-free patients with higher insulin concentrations (top tertile) compared to those with lower insulin concentrations over a 22-year follow-up (Furie 2008; Pyorala 2000). Refer to the Diabetes protocol for more information.
Many aging individuals suffer from episodic breathing lapses during sleep. This is called sleep apnea. The most common form of sleep apnea occurs when the upper airway collapses (partially or completely) for intermittent periods. This results in characteristic gasping or choking during nighttime breathing (Das 2012).
Sleep apnea deprives its victims of oxygen during sleep. Lack of oxygen due to sleep apnea is associated with inflammation, endothelial dysfunction, and oxidative stress. All of these factors compromise the integrity of blood vessels, increasing the likelihood a stroke-causing blood clot will form. Sleep apnea is independently associated with significantly increased stroke risk, ranging from about 1.5-fold to over 4-fold across several studies, but also may aggravate stroke risk factors such as high blood pressure, atrial fibrillation, and diabetes (Das 2012). One study showed that people with sleep apnea are more likely to die within the first month following stroke than those who breathe normally during sleep (Mansukhani 2011).
Many people with sleep apnea may not know they have it. Participating in a clinical sleep study is the most accurate way to assess sleep quality. Identification and correction of sleep apnea can significantly reduce overall cardiovascular risk (Buchner 2007).