Carbohydrates and heart disease

Atherogenic dyslipidemia is a lipoprotein profile that predisposes one to cardiovascular disease. Grundy (1997) characterizes it by four markers: 1) a borderline high-risk LDL cholesterol (130 to 159 mg/dL), 2) moderately raised (often high normal) triglycerides (greater than 150 mg/dL), 3) small LDL particles, and 4) low HDL cholesterol (less than 40 mg/dL for men and 50 mg/dL for women). The third marker is due to data indicating that not all LDL particles are atherogenic; a preponderance of small, dense LDL particles (known as a pattern B phenotype) is associated with increased coronary artery disease (Austin et al., 1988). The presence of atherogenic dyslipidemia itself is a marker for metabolic syndrome.

Source:

Ronald Krauss and colleagues have convincingly shown that changes in carbohydrate intake profoundly affects LDL phenotypes (reviewed in Krauss, 2001). The figure below is a nice summary of the basic observation that restricting carbohydrates reduces the incidence of the atherogenic LDL particle pattern. Note especially the apparent continuity of the effect, and the fact that the carbohydrates are not even severely restricted (certainly nowhere near the levels required to induce ketosis). If you have a half hour to spare, you can catch a recent webcast talk by Krauss summarizing the Pathophysiology of Atherogenic Dyslipidemia.

Source: Krauss, 2001

If you want to full scoop on recent research on the relationship between carbohydrates and dyslipidemia and metabolic syndrome, definitely take the time to check out this review article from Jeff Volek and colleagues (it's technically still in press, but you can grab the galley proofs online). It covers a lot of ground, and is well worth the effort.

Dietary carbohydrate restriction induces a unique metabolic state positively affecting atherogenic dyslipidemia, fatty acid partitioning, and metabolic syndrome.

Volek JS, Fernandez ML, Feinman RD, Phinney SD.

Department of Kinesiology, University of Connecticut

Abstract: Abnormal fatty acid metabolism and dyslipidemia play an intimate role in the pathogenesis of metabolic syndrome and cardiovascular diseases. The availability of glucose and insulin predominate as upstream regulatory elements that operate through a collection of transcription factors to partition lipids toward anabolic pathways. The unraveling of the details of these cellular events has proceeded rapidly, but their physiologic relevance to lifestyle modification has been largely ignored. Here we highlight the role of dietary input, specifically carbohydrate intake, in the mechanism of metabolic regulation germane to metabolic syndrome. The key principle is that carbohydrate, directly or indirectly through the effect of insulin, controls the disposition of excess dietary nutrients. Dietary carbohydrate modulates lipolysis, lipoprotein assembly and processing and affects the relation between dietary intake of saturated fat intake and circulating levels. Several of these processes are the subject of intense investigation at the cellular level. We see the need to integrate these cellular mechanisms with results from low-carbohydrate diet trials that have shown reduced cardiovascular risk through improvement in hepatic, intravascular, and peripheral processing of lipoproteins, alterations in fatty acid composition, and reductions in other cardiovascular risk factors, notably inflammation. From the current state of the literature, however, low-carbohydrate diets are grounded in basic metabolic principles and the data suggest that some form of carbohydrate restriction is a candidate to be the preferred dietary strategy for cardiovascular health beyond weight regulation.

PMID: 18396172

Monitoring health by counting heartbeats

It's often the case that high-intensity workouts (like Fran or Tabata sprints) cause your heart rate to skyrocket in order to meet the metabolic demands of active muscle. Remarkably, the flow of blood to active muscles may increase to four or five times that of resting cardiac output. Just as remarkable is the fact that your heart rate will typically drop 40% five minutes after exercise completion. These dramatic changes in heart rate are controlled by the sympathetic and parasympathetic components of the autonomic nervous system; sympathetic activation increases cardiac acceleration, contractility and coronary constriction whereas parasympathetic activation promotes cardiac deceleration and coronary dilation. Your heart rate response to exercise is largely determined by the balance of these two systems.

Being a sucker for numbers, I'm always on the lookout for simple, predictive physiological measures. There are a few based on heart rate that are strongly predictive of mortality and turn out (not surprisingly) to be modifiable by training. The first is resting heart rate, which the American Heart Association suggests should be between 60-80 beats per minute (bpm). A fast heart rate is associated with an increased risk of death from cardiovascular as well as noncardiovascular causes (Hjalmarson, 2007; Palatini, 1999). Even within the recommended range (60-80 bpm), a lower resting heart rate is significantly associated with decreased risk of dying from any cause, especially heart attack (Jouven et al., 2005).

The second measure is heart rate reserve, the difference between maximal heart rate and resting heart rate. A smaller dynamic range is associated with increased risk of death from any cause, especially heart attack (Jouven et al., 2005), and a failure to reach predicted peak heart rates during graded exercise is predictive of increased mortality and coronary heart disease incidence (Lauer et al., 1996).

Finally, the last measure is heart rate recovery, the difference between maximal heart rate and heart rate measured some fixed time after cessation of exercise (usually 1 or 2 minutes). The failure to drop at least 30 bpm within 1 minute is associated with increase risk of heart attack. A smaller decrease in heart rate suggests a dysfunction of the parasympathetic system, since the decrease in heart rate immediately following exercise is primarily due to parasympathetic reactivation (Imai et al., 1994; Raymond, 2004).

The above figure bins together all the data below 25 bpm recovery, but if you look more closely at lower ranges, an association with risk of death is even more apparent. For all you stats geeks, below is a conditional trellis plot (click the figure to see a larger version) that illustrates risk of all-cause mortality as a function of age, fitness, peak heart rate and heart rate recovery (Ishwaran et al., 2004). Age is a binary grouping indicated by the orange bars (left column is younger than 45 yo and the right column is older than 45 yo). Fitness is a categorical variable indicated by the green bars (least fit in the top row proceeding to most fit in the bottom row). Peak heart rate and heart rate recovery (measured 1 minute after ceasing exercise) are plotted for each subject for whichever panel they correspond to (age x fitness). That's five freakin variables!

And just for kicks, the figure to the right plots some data from the last time I did 400 meter sprints. There goes (220-age) as a predictor for my maximal heart rate! There are better ways of estimating maximal heart rate (e.g., see Joe Friel's work).

It's worth pointing out that these heart rate measures are not independent (Jouven et al., 2005); in fact they're highly correlated, suggesting that they may be different measures of the same disorder. And while the mechanism(s) underlying the association of these heart rate measures with increased mortality and heart disease remain unknown, the data are consistent with the idea that autonomic system imbalance predisposes people to life-threatening arrythmias (Jouven et al., 2005).

Aside from their utility for predicting death, these measures are also interesting because they can be modified by training. Following training, heart rate recovery is accelerated (Darr et al., 1988; Imai et al., 1994; Sugawara et al., 2001) and resting heart rate is decreased (Wilmore et al., 2008). Changes to maximal heart rate are less clear, with some evidence for a slight decrease following endurance training (Darr et al., 1988; Wilmore et al., 2008). So if you're bored, or looking for another way to track progress, break out the stopwatch or heart rate monitor and start logging! Indeed, Levine (1997) showed that the total number of heartbeats in a lifetime is remarkably constant across a wide range of variation in mammals.If we take seriously the idea that a human heart is physiologically predetermined to beat ~3 billion times in a lifetime, perhaps it wouldn't hurt to make reducing your resting heart rate an objective.

Get fat!

Good fats of course, those being ω-3 fatty acids (a type of polyunsaturated fatty acid [PUFA], another being the ω-6 fatty acids; these are also referred to as n-3 and n-6 fatty acids). Members of these families are derived from the essential fatty acids linoleate (LA) and α-linolenate (LNA). Strictly speaking, these two are the only essential fatty acids (required through diet), although that term is often extended to the entire family of PUFAs (Cunnane, 2003). The ω-3 and ω-6 fatty acids are critical for a host of bodily functions, which you can read about in reviews by Das (2006) and Wijendran and Hayes (2004). Very roughly speaking ω-6 fatty acids are pro-inflammatory whereas ω-3 fatty acids are anti-inflammatory. More specifically, the ω-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are antithrombotic and antiarryhthmic, and dietary intake of these fatty acids is associated with reduced risk of death from cardiovascular disease.

Source: Mozaffarian and Rimm 2006.

Although current evidence indicates that the relative dietary ratios of ω-3 and ω-6 fatty acids is a indicator for overall health (Wijendran and Hayes 2004; Simopoulos, 2002), the mechanisms by which EPA and DHA reduce the risk of cardiac mortality remain unclear. The assumption is that direct incorporation of these fatty acids into the myocardium of the heart underlies their health benefits. That dietary intake directly modulates myocardial phospholipid profile was recently documented by Metcalf et al. (2007). The authors examined the atrial tissue of people undergoing elective cardiac surgery following varying durations of dietary supplementation with fish oil (6 g EPA+DHA/day, for 7-60 days). They found that fish oil supplementation increased the amount of EPA and DHA in the cell membranes of both atrial tissue as well as red blood cells.


It has been proposed that the cardioprotective effects of EPA and DHA result from replacement of arachidonic acid (AA) in cardiac membranes. AA is a precursor of a wide array of eicosanoids (Funk, 2001). These compounds promote inflammatory responses, platelet aggregation, and vasoconstriction. Although these are essential metabolic functions, excess AA-derived eicosanoids can promote atherosclerotic disease and thrombosis.

Source: Calder 2006.

Metcalf et al. also showed that dietary fish oil supplementation reduced atrial AA concentrations, consistent with the idea that part of the benefit of EPA and DHA may be due to the reduction in AA-derived pro-inflammatory factors.


These phosphospholipid adaptations in atrial tissue may thus underlie the cardioprotective effects of dietary fish oil. In support of this, the timescale and magnitude of these changes is broadly consistent with the observation that the protective effects of ω-3 fatty acid supplementation begin early, but reach significance only after about three months.

Source: Marchioli et al. 2002.

Also of note is the fact that supplementing with flaxseed oil (high in ALA) did not result in any changes in ω-3 fatty acid concentrations. This is likely due to the fact that dietary ALA is converted to EPA and DHA at extremely low rates (Plourde & Cunnane 2007), which is consistent with suggestions that ALA supplementation is not cardioprotective (Matthan et al. 2005; Wang et al. 2006).

I hate running

Warm-up:
0.5 mi jog

WOD 070830
Run 5k
25:49

2x1 min front planks
3x8 (per arm) windmills (30# KB)

Ran on a treadmill (1% incline, set between 7.1-7.6). I didn't find this fun at all, was really thinking I could stick to a 8'/mi pace. Guess it's time to work more aerobic conditioning in. I wore a heart rate monitor, and it was consistently above 170 bpm, peaking at 202 bpm. This seems abnormally high for such slow running?? Poor efficiency?

Mean heart rates recorded during 10 minutes of recovery after peak exercise, sorted by age and training status. Source: Darr et al., 1988.

What is the best way to recover?

Interesting point by Rippetoe on the CrossFit boards today:
"I'd like to see CFers stop laying down at the end of a workout like that. The highest incidence of arrythmias associated with exercise occur in this situation. It is far better to walk it off than it is to assume a position in which venous return to the heart is compromised at a terribly critical time by a cessation of contraction in the biggest muscles working in the exercise."

In response to Rippetoe, 'bingo' noted "I asked a cardiologist buddy for his take and he was rather adamant that arrhythmia risk is overwhemingly low and overwhelmingly outweighed by the risk of loss of conciousness from remaining upright."

I guess that's why everyone is always saying to "walk it off". This prompted some searching that led to a couple of interesting reads (linked below), which, of course, reveal that the body is a complex machine. Hmmm, hydrostatic column, hmmm, intrabdominal pressure from diaphragmatic descent, hmmm, maybe I should move my legs while laying down? Nah, I'll just lay down; if it mattered, I'd be cooked by now anyways.

Miller JD, Pegelow DF, Jacques AJ, Dempsey, JA.
Skeletal muscle pump versus respiratory muscle pump: modulation of venous return from the locomotor limb in humans. J Physiol. 2005 March 15; 563(Pt 3): 925–943.

Hogan MC, Grassi B, Samaja M, Stary CM, Gladden LB.
Effect of contraction frequency on the contractile and noncontractile phases of muscle venous blood flow. J Appl Physiol. 2003 Sep;95(3):1139-44.

Eat those fruits and vegetables!

First in a series devoted to reducing risks of death.
If you had any doubt that eating fruits and vegetables is beneficial to your health, maybe some data will convince you.
Sidebar: You can skip this on first read, but here are some links to potentially unfamiliar terms. If you aren't familiar with study designs, have a quick here. If you aren't used to thinking about relative risk (don't confuse them with odds ratios), have a look here. Most of the data presented below came from prospective cohort studies with large cohorts and long-term follow ups. I chose primarily meta-analyses to get better power and lower bias (although you may want to check the citations to see the specifics of how studies were selected for inclusion).
The figure below summarizes a meta-analysis of prospective cohort studies (Hu & Willett, 2002) examining the effect of eating nuts, fruits and vegetables or whole grains on cardiovascular disease. The relative risks were derived from the comparison of the incidence rates between the highest and lowest consumption groups (quintiles, quartiles or specific intake categories as per specific study) and were adjusted for nondietary and/or dietary covariates. These are huge effects.

So it's pretty clear that eating nuts, fruits and vegetables or whole grains can reduce your risk of cardiovascular disease. However, the comparison above is basically between eating lots versus eating little of any of these food categories. You might be wondering whether there is a dose-dependence for reducing risk. The following figure comes from another meta-analysis of prospective cohort studies (He et al., 2007), and focuses on fruit and vegetables. Here the risk ratios were derived from comparing the highest categories of fruit and vegetable consumers (3-5 servings/day and >5 servings per day) against lower intakes (<3 and="" cardiovascular="" class="separator" day="" disease.="" div="" eat="" fruits="" group="" lower="" more="" of="" risk="" servings="" style="clear: both; text-align: center;" the="" vegetables="" you="" your=""> What about other diseases? Well, it probably shouldn't surprise you that eating fruits and vegetables also reduces your risk of stroke, the third leading cause of death (nipping at the heels of CHD and cancer). The figure below summarizes a meta-analysis of prospective cohort studies (He et al., 2006) on the effects of eating fruits and vegetables on stroke. Note that were looking only at the top consumers (as in the immediately preceding figure). Again, we're seeing a nice dose-dependent effect of eating fruits and vegetables on reducing your risk of stroke (both ischaemic and haemorrhagic).

This dose-dependence is more clearly illustrated in a similar meta-analysis (Dauechet et al., 2005). The following is a summary figure, which further breaks down the data by fruits alone, vegetables alone and fruits+vegetables. The size of the bubbles is inversely proportional to the variance of the relative risk of each study, bigger bubbles=more reliable study. Looks like it "eat your fruits and vegetables, but more of those fruits".

I'm off to eat a bushel of apples.

Never again

Warm-up:
10-5-5-5-5 overhead squat (45,65,85,95)

WOD from 062707

3 rounds for time:
50 thrusters (45# bar)
35 pullups

35:50

Heart rate at 204 BPM at the end of last set of thrusters (apparently I still have β-adrenergic receptors on my heart despite my age). Forced to use Gravitron due to total muscular failure (aka pussyarms). Everything hurts.

Should only be done in groups.Source: Higginbotham et al., 1986