JoPo Fo Sho

"Here Am I"

Tue, 29 May 2012 13:27:00 -0400

"Here Am I"

Mousetrap

Mon, 21 May 2012 19:08:48 -0400

Mousetrap

"The glory of Christianity is to conquer by forgiveness."

Fri, 18 May 2012 12:53:07 -0400

“The glory of Christianity is to conquer by forgiveness.”

- William Blake

"We get our moral bearings by looking at God. We must begin with God."

Mon, 14 May 2012 00:46:54 -0400

“We get our moral bearings by looking at God. We must begin with God.”

- Aiden Wilson Tozer, The Pursuit of God

"Every heresy begins with a good illustration."

Sat, 12 May 2012 15:25:00 -0400

“Every heresy begins with a good illustration.”

- G. Stephen Kinnard

The Cross as the End of the World

Thu, 10 May 2012 10:36:46 -0400

The Cross as the End of the World

#adultsontheinternet

Thu, 10 May 2012 10:29:13 -0400

[Name withheld]: What is it with the pound sign (#) in front of words now?? I don't get it...new trend???

“Somebody That I Used to Know” (Cover), Walk off the...

Thu, 10 May 2012 09:34:27 -0400

“Somebody That I Used to Know” (Cover), Walk off the Earth

"If God is not, then the existence of all that is beautiful … is but the accidental and..."

Wed, 09 May 2012 13:18:00 -0400

“If God is not, then the existence of all that is beautiful … is but the accidental and ineffective by-product of blindly swirling atoms…. A man may well believe that this dreadful thing is true. But only the fool will say in his heart that he is glad that it is true. For to wish there should be no
God is to wish that the things which we love and strive to realize and make permanent, should be only temporary and doomed to frustration and destruction. If life and its fulfilments are good, why should one rejoice at the news that God is dead and that there is nothing in the whole world except our frail and perishable selves that is concerned with anything that matters?”

- William Pepperell Montague, Belief Unbound

How Can the Bible Be Authoritative?

Wed, 09 May 2012 11:47:46 -0400

How Can the Bible Be Authoritative?:

Worth thinking through.

"[Our Lord] saith thus: Pray inwardly, though thou thinkest it savour thee not: for it is profitable,..."

Tue, 08 May 2012 10:34:05 -0400

“[Our Lord] saith thus: Pray inwardly, though thou thinkest it savour thee not: for it is profitable, though thou feel not, though thou see nought; yea, though thou think thou canst not. For in dryness and in barrenness, in sickness and in feebleness, then is thy prayer well-pleasant to me, though thou thinkest it savour thee nought but little. And so is all thy believing prayer in my sight.”

- Julian of Norwich, Revelations of Divine Love

"Do not waste time bothering whether you ‘love’ your neighbor; act as if you did…. When you are..."

Tue, 08 May 2012 10:10:00 -0400

“Do not waste time bothering whether you ‘love’ your neighbor; act as if you did…. When you are behaving as if you loved someone you will presently come to love him.”

- Clive Staples Lewis, Mere Christianity

"There’s only one God, ma’am, and I’m pretty sure He doesn’t dress like that."

Sun, 06 May 2012 21:08:56 -0400

“There’s only one God, ma’am, and I’m pretty sure He doesn’t dress like that.”

- Captain America

RLS and Cardiovascular Disease

Sat, 05 May 2012 11:59:00 -0400

J. Joseph Porter

Science of Living Systems 17. The Human Organism

Professor Joseph Brain

Section Leader: Orfeu Buxton

May 5, 2012

Restless Leg Syndrome and Cardiovascular Disease

What exactly is the relationship between restless leg syndrome (RLS) and cardiovascular disease (CVD)? In this paper, recent literature on this relationship will be examined and reviewed, and avenues of potentially fruitful future research will be discussed.

RLS is associated with increased incidence of CVD (Winkelman et al., 2008). (Winkelman defines CVD as coronary artery disease – physician-diagnosed angina, myocardial infarction, coronary revascularization procedure – or history of physician-diagnosed stroke or heart failure.) In certain circumstances, the odds ratio of CVD for people with RLS is over 2.00; in other words, even after adjustment for age, sex, and other factors, people with RLS are over twice as likely to have CVD as people without RLS. However, the precise nature of the relationship between RLS and CVD is unclear. The causal direction between the two has not yet been determined: It is not yet known whether RLS causes CVD, whether CVD causes RLS, or (perhaps) whether some third condition or factor causes both. One main question to be addressed in this paper, then – if not the main question – is how exactly to come to a better understanding of the relationship between RLS and CVD.

Determining the nature of the relationship between RLS and CVD is important both for personal reasons and for reasons related to public health. On a personal level, it is important both because a relative of mine has RLS and because I (though I have never been diagnosed with RLS) exhibit symptoms that lead me to believe that I may very well have RLS. Consequently, I have an interest in establishing whether or not my relative and I are at a greater risk for CVD (as would be the case if RLS causes CVD), so that this risk can be minimized. This issue is also important more generally because RLS is a very common neurological disorder – different studies generally evaluate its prevalence as being between 4% and 10% (Allen et al., 2009; Phillips et al., 2006; note that this variation may be partly the result of different methodologies across different studies) – and because CVD is a leading cause of death in the United States. As a result, understanding the relationship between the two conditions could have important implications for treatment and prevention: for example, implications for people for whom treatment or prevention of RLS could subsequently minimize risk for CVD.

RLS is “a sensorimotor disorder characterized by a distressing urge to move the legs and, sometimes, other parts of the body, such as the arms” (Hening et al., 2007). Because no laboratory findings are specific for RLS – there is no “RLS test” in the way that there is, for instance, a strep test for strep throat – the diagnostic criteria for RLS are the presences of four symptoms: (1) urge to move the legs, usually with dysesthesias (unpleasant sensations variously described as burning, tingling, or creeping); (2) onset or exacerbation with rest; (3) relief with movement; and (4) circadian pattern (ibid.). A mnemonic device for these four criteria is “URGE”: (1) “urge to move”; (2) “rest induced”; (3) “gets better with activity”; and (4) “evening and night accentuation.” In addition, periodic limb movements in sleep (PLMS) – defined as movements during sleep lasting 0.5 to 5 seconds, separated by intervals of 4 to 90 seconds, and occurring in series of at least four consecutive movements – occur in about 80% of people with RLS (Montplaisir et al., 1997). It is known that relatives of people with RLS are much more likely to have RLS than those whose relatives do not have it; this genetic etiology, however, does not yet constitute a full explanation of the primary cause of RLS (Allen et al., 2002).

The quality of life of people with RLS is severely affected. Even disregarding potential risks related to CVD, “RLS affects quality of life at least as severely as other common chronic disorders” (Earley and Silber, 2010). It is an important cause of insomnia, and it has also been linked to anxiety and to depression (ibid.). Moreover, lack of sleep due to RLS symptoms may lead to persistent daytime tiredness, irritability, lack of motivation, and impaired memory and concentration (Lasch 2011). Perhaps most important among the consequences of RLS, however, is the doubled risk for CVD – assuming that RLS causes CVD.

What is currently known about the relationship between RLS and CVD? In all likelihood, the most comprehensive study to date on this issue is Winkelman’s Sleep Heart Health Study. In this study, Winkelman evaluated the cross-sectional association between RLS and CVD in a pool of over 3,000 middle-aged and elderly subjects with a mean age of 67.9 (Winkelman et al., 2008). After adjustment for age, sex, race, and several known risk factors for CVD (body mass index, diabetes mellitus, systolic blood pressure, antihypertensive medication use, total to high-density lipoprotein cholesterol ratio, and smoking history), the odds ratio for CVD was 2.07 for subjects with RLS compared to those without it (ibid.). Put differently, one person of the same age, sex, race as another person and with the same presence of CVD risk factors as that other person was 2.07 times as likely to have CVD as the other person. The association of RLS with CVD was similar for both men and women, but disappeared entirely for subjects under the age of 65 in comparison to those over the age of 65 (ibid.). Furthermore, the association of RLS with CVD

was considerably stronger in those with RLS symptoms that occurred more than 15 times per month than in those whose symptoms occurred less frequently. Similarly, the association of RLS with … CVD was stronger in those who reported that their RLS symptoms were ‘a lot’ or ‘extremely’ bothersome than in those who reported it to be only ‘moderately’ bothersome. On the other hand, among those with RLS, self-reported duration of symptoms was not significantly associated with … CVD (ibid.).

Winkelman’s findings corroborate previous epidemiologic studies that have demonstrated a similar association of RLS with CVD (ibid.).

RLS, then, is associated with a twofold risk of CVD. However, Winkelman’s data do not establish any specific causal relationship underlying the association of RLS with CVD, only a strong correlation between the two (ibid.). Various possible causal mechanisms have been put forth to explain this correlation.

One main explanation involves PLMS. A vast majority of people with RLS display PLMS, and PLMS lead to “upticks” in nocturnal blood pressure: brief increases in both systolic blood pressure (of about 22 mmHg) and diastolic blood pressure (of about 11 mmHG) following limb movements in sleep (Pennestri et al., 2007). These upticks, which last for about 15 heartbeats (less than a minute each), could increase risk for CVD; various studies have demonstrated an association of such fluctuations in blood pressure with vascular and cardiac damage, as well as with stroke (ibid.). However, data from Winkelman’s study demonstrate only a weak and statistically insignificant relationship between RLS and hypertension (defined either by use of antihypertensive medications or by elevated blood pressure): The odds ratio of hypertension was only 1.30 for those with RLS compared to those without it, a statistically insignificant value (Winkelman et al., 2008). Moreover, adjusting for systolic blood pressure and use of antihypertensive medications did not diminish the association of RLS with CVD, a fact which indicates that hypertension does not causally contribute to this association (ibid.). However, upticks in nocturnal blood pressure could still plausibly increase risk for CVD even in the absence of hypertension “by increasing the 24-hour blood pressure profile without producing changes in daytime blood pressure” (ibid.).

Alternatively, RLS’ impact on sleep quality and quantity could increase risk for CVD (ibid.). RLS negatively affects sleep, and at least one study has indicated that short sleep duration is associated with coronary heart disease (defined in that study based on self-reported diagnosis or medical history of coronary events) (Ayas et al., 2003). However, in Winkelman’s study, total sleep time was similar for those with RLS and those without RLS, and adjustment for sleep latency (self-reported time required to fall asleep), total sleep time, and insomnia did not affect the odds ratio for CVD for those with RLS – both facts which suggest that factors related to sleep also do not causally contribute to the association of RLS with CVD (Winkelman et al., 2008).

The causal direction could also move from CVD to RLS. Winkelman gestures to vascular alterations in the central nervous system or peripheral vasculature associated with CVD and medications used in treatment of CVD as potential causes of RLS, but does not explain how such alterations or medications could produce RLS symptoms, and notes that correction for use of antihypertensive medications did not substantially change the odds ratio for CVD for those with RLS (ibid.). Finally, confounding by some unmeasured factor such as iron deficiency or renal failure could play a role in the association of RLS with CVD, but candidates for such an unmeasured factor are not prevalent enough to account for the strong observed association (ibid.).

Existing studies on the relationship of RLS and CVD are limited in many ways. End-stage renal disease, pregnancy, and iron deficiency are known secondary causes of RLS, but the primary cause of RLS is still unknown, and many disorders have clinical features that mimic those of RLS (Hening et al., 2007; Miletić and Relja, 2011). Furthermore, no definitive “RLS test” exists. All of these factors complicate diagnosis of RLS, especially when made by questionnaire rather than by interview, as was the case in the Winkelman study (Winkelman et al., 2008). In fact, different diagnostic methods across studies pose another challenge to current research into RLS, even if diagnostic criteria have recently been standardized. For instance, Ohayon and Roth’s study of over 18,000 people who underwent telephone interviews determined that the odds ratio of heart disease (as self-reported in the interviews) was 1.41 for those with RLS, but used different diagnostic criteria for RLS than those used by Winkelman – and no apparent criteria for heart disease (Ohayon and Roth, 2002).

Incomplete understanding of the causes of RLS, in addition to complicating accurate diagnosis of RLS, also complicates analysis of the causal relationship between RLS and CVD (and, indeed, analysis of the causal relationship between RLS and any other condition). The reason for this is clear enough: If it is not yet known what exactly causes RLS, it is difficult to ascertain how CVD could cause RLS, or how some third condition might causally contribute to their association. Moreover, if it is not yet known what exactly causes RLS, it is difficult to ascertain why the association of RLS with CVD is stronger in those whose RLS symptoms are more frequent or more intense. Understanding what causes RLS – and understanding, in turn, why individual cases of RLS vary in the frequency and intensity of their symptoms – is consequently vital.

Finally, CVD is, sometimes by necessity, rather loosely defined in the Winkelman study (and elsewhere). Winkelman considers CVD present in subjects who self-reported any one of a number of different conditions in their medical histories, whether those conditions were present in those subjects a short time ago or decades ago. This definition fails to distinguish between “actual” cardiovascular disease and past cardiovascular disease; put differently, it fails to distinguish between those patients who are currently at high risk for some condition included in the CVD umbrella and those patients who were formerly (but perhaps no more) at high risk for some such condition. Given that the odds ratio of CVD for those with RLS was highly age-dependent (a fact that could be explained by a latent period in increased risk for CVD among those with RLS, or vice versa), distinguishing between current and former risk for CVD could be indispensable for determining the causal relationship between RLS and CVD.

Moving forward, many clear options for further research into the relationship between RLS and CVD remain. Most obviously, continued research into the primary cause of RLS is necessary, as a means of better understanding both RLS itself and RLS as it relates to CVD. Identifying a primary cause of RLS could shed light on this issue. Furthermore, several studies could be devised to explore the relationship between RLS and CVD more closely. One such study could compare CVD rates in people diagnosed with and treated for RLS to CVD rates in people diagnosed with RLS who were not treated for their RLS. If RLS causes CVD, then the former group of people should be at a lower risk for CVD than the latter group (especially as the amount of time since treatment increases), because the members of the former group have had their RLS treated; however, if CVD causes RLS, then the two groups should have similar CVD rates. One problem for this potential study is that current treatments for RLS are either inconsistently effective or limited by potent side effects such as impulse control disorders (Easley and Silber, 2010). Another possible study could compare RLS rates in people before and after acquiring CVD. If RLS rates increase disproportionately after CVD, then it is likely that CVD causes RLS; if they do not, then some other causal relationship must exist. Even data gathered from questionnaires distributed to people with CVD about their sleeping patterns before and after acquiring CVD could be instructive. In addition, studies could be designed to test specific causal hypotheses individually. For example, a study that compared CVD rates in RLS subjects who do not experience PLMS to CVD rates in RLS who do could test the hypothesis that the association of RLS and CVD is the result of blood pressure fluctuations brought about by PLMS. If RLS subjects who do not experience PLMS have significantly lower CVD rates than those who do, then it is likely that PLMS is part of the causal mechanism underlying the relationship between RLS and CVD. Undoubtedly, then, many avenues of investigation into this subject exist.

In conclusion, it is clear that there is a strong association of RLS with CVD: After adjustment for demographic and CVD risk factors, the odds ratio for CVD is approximately 2.00 for people with RLS compared to those without RLS. The association is absent among people under the age of 65, and it increases in strength among people whose RLS symptoms are very frequent or intense. The causal direction of this association is unclear, although several hypotheses regarding it exist, different ones of which posit a causal direction from RLS to CVD (as a result, e.g., of increases in nocturnal blood pressure due to PLMS), from CVD to RLS (as a result, e.g., of hypertensive medication), and from some third factor to both RLS and CVD (as a result, e.g., of iron deficiency). Current studies into the causal relationship between RLS and CVD are limited by several factors, including the difficulty of accurately diagnosing RLS, incomplete understanding of the causes of RLS, and relatively vague definitions of CVD. Future research should attempt to identify a primary cause of RLS and explore different means of identifying the causal direction in the association of RLS with CVD, because coming to a better understanding of this causal relationship could have important implications for treatment or prevention.

When someone asks if i can help them finish their food

Fri, 04 May 2012 00:08:11 -0400

mylifeasmeangirls:

Bible Interpretation Methods You Should Avoid

Thu, 03 May 2012 20:53:34 -0400

Bible Interpretation Methods You Should Avoid

Time to Turn!

Thu, 03 May 2012 17:16:15 -0400

Time to Turn!

American Giving

Thu, 03 May 2012 09:51:17 -0400

American Giving:

(Hat tip to BC.)

Why Are Donations to Government So Small?

Thu, 03 May 2012 09:49:59 -0400

Why Are Donations to Government So Small?

"The worst error is to imagine that a Christian must try to be ‘sane’ like everybody..."

Wed, 02 May 2012 09:55:29 -0400

“The worst error is to imagine that a Christian must try to be ‘sane’ like everybody else, that we belong in our kind of society.”

- Thomas Merton, Raids on the Unspeakable