Friday Five #10: Chimps, Heart Disease, and your future career

1) Chimpanzee and human Y chromosomes are remarkably divergent in structure and gene content: You had to be on Mars to miss this one this week. An article appeared in Nature that demonstrated that the Y-chromosome between Chimps and Humans was highly divergent, on the lines of 310 millions years so there is more similarity between chickens and human males (may explain my inexplicable desire to look like Colonel Sanders) then between chimps and humans. Here is the abstract.

The human Y chromosome began to evolve from an autosome hundreds of millions of years ago, acquiring a sex-determining function and undergoing a series of inversions that suppressed crossing over with the X chromosome^{1, 2}. Little is known about the recent evolution of the Y chromosome because only the human Y chromosome has been fully sequenced. Prevailing theories hold that Y chromosomes evolve by gene loss, the pace of which slows over time, eventually leading to a paucity of genes, and stasis^{3, 4}. These theories have been buttressed by partial sequence data from newly emergent plant and animal Y chromosomes^{5, 6, 7, 8}, but they have not been tested in older, highly evolved Y chromosomes such as that of humans. Here we finished sequencing of the male-specific region of the Y chromosome (MSY) in our closest living relative, the chimpanzee, achieving levels of accuracy and completion previously reached for the human MSY. By comparing the MSYs of the two species we show that they differ radically in sequence structure and gene content, indicating rapid evolution during the past 6 million years. The chimpanzee MSY contains twice as many massive palindromes as the human MSY, yet it has lost large fractions of the MSY protein-coding genes and gene families present in the last common ancestor. We suggest that the extraordinary divergence of the chimpanzee and human MSYs was driven by four synergistic factors: the prominent role of the MSY in sperm production, ‘genetic hitchhiking’ effects in the absence of meiotic crossing over, frequent ectopic recombination within the MSY, and species differences in mating behaviour. Although genetic decay may be the principal dynamic in the evolution of newly emergent Y chromosomes, wholesale renovation is the paramount theme in the continuing evolution of chimpanzee, human and perhaps other older MSYs.

2) Telomere Length Trajectory and Its Determinants in Persons with Coronary Artery Disease: Longitudinal Findings from the Heart and Soul Study A good study that looks at telomere length and risk of cardiovascular disease. Telomeres are a good indicator of biological aging. They are basically the ends of chromosomes and as you age and the body replenishes cells through meiosis they begin to degrade.

Background

Leukocyte telomere length, an emerging marker of biological age, has been shown to predict cardiovascular morbidity and mortality. However, the natural history of telomere length in patients with coronary artery disease has not been studied. We sought to investigate the longitudinal trajectory of telomere length, and to identify the independent predictors of telomere shortening, in persons with coronary artery disease.

Methodology/Principal Findings

In a prospective cohort study of 608 individuals with stable coronary artery disease, we measured leukocyte telomere length at baseline, and again after five years of follow-up. We used multivariable linear and logistic regression models to identify the independent predictors of leukocyte telomere trajectory. Baseline and follow-up telomere lengths were normally distributed. Mean telomere length decreased by 42 base pairs per year (p<0.001). increase =" 7.6;" years =" 1.6;" or =" 2.4;" increase =" 1.4;">

Conclusions/Significance

Leukocyte telomere length may increase as well as decrease in persons with coronary artery disease. Telomere length trajectory is powerfully influenced by baseline telomere length, possibly suggesting negative feedback regulation. Age, male sex, and abdominal obesity independently predict telomere shortening. The mechanisms and reversibility of telomeric aging in cardiovascular disease deserve further study.

3) 'Missing Link' Between Heart Failure and Environment Discovered : Similiar to the article above, this looks at the link between DNA methlyation and heart failure. Throughout most of your life certain genes or portions of genes that are not supposed to be copied are halted through methalyation or they are told you are a heart muscle cell - please stay a heart muscle cell. This is an interesting study as it indicates epigeneitic (an overused buzz word that sounds smarter than envionment).

4) U.S. Adult Obesity Still High, but Recent Data Suggest Rates May Have Stabilized A news item that mentions that obesity is still very high in the US but it seems to have stabilized, but of course this could go either way.

5) Future jobs: what might you be doing? What do you want to be in the future. Here I was hoping to do be sitting in the lab of luxury, pushing buttons ala George Jetson.

Life Expectancy in the US is unequal between regions

PLos Medicine has an interesting article on Life expectancy from birth in the US using mortality data at the county level. We all know that life expectancy has been increasing since 1960 (7yrs for men, 6 yrs for women) but what they find is that this is not always the case. If you look at the figure below you see that on average life expectancy increased from 1961-1983 nationwide but from 1983-1999 you see a steep decline (primarily in women) in the worst-off counties. The authors find that this result is due to halt in the reduction of cardiovascular disease, and a rise in lung cancer, COPD, and diabetes in both sexes along with an increase HIV/AIDS and homicide in men.

Counties are categorized into six groups on the basis of how their life expectancy changed in relation to national sex-specific change in life expectancy (4.1 y for men and 4.8 y for women in 1961–1983; 3.1 y for men and 1.3 y for women in 1983–1999). Actual life expectancies are shown in Figure S1, and absolute changes in life expectancy are shown in Figure S2.

Group 1, life expectancy increased at a level significantly higher than the national sex-specific mean; group 2, life expectancy increased at a level significantly higher than zero but not significantly distinguishable from the national sex-specific mean; group 3, life expectancy increased at a level significantly higher than zero but significantly less than the national sex-specific mean; group 4, life expectancy change was statistically indistinguishable from zero and from the national sex-specific mean; group 5, life expectancy change was statistically indistinguishable from zero and was significantly less than the national sex-specific mean; group 6, life expectancy had a statistically significant decline. All statistical significance was assessed at 90%.

Cholesterol and the media

The media is currently bombarding the internet with a recent study published in the New England Journal of Medicine regarding a class of cholesterol lowering drugs known as Ezetimibe (Vyotrin, Zetia) and that the public is being lied too. An example of this media outrage can be found here in the New York Times or pretty much any other of a host of news outlets.

This study investigated the impact of a class of drugs known as Ezetimibe in patients with familial hypercholesterolemia. These drugs were designed to be used in conjunction with statins as a way to lower Low Density Lipoprotien cholesterol (LDL-C). Opposed to statins which impede a key biochemical pathway in the liver (HMG-CO-A), these drugs inhibit the absorption of cholesterol by binding to Niemann–Pick C1-like 1 (NPC1L1) protein (Niemann-Pick disease is an autosomal recessive disease). The reason an individual takes cholesterol lowering drugs is to reduce plaques that occur in arteries, which is apparently not the case here. Anyone who has watched TV in the last 20 years has realized that we are bombarded with ambiguous prescription drug ads and an earlier article compared the prescription rate between the U.S. and Canada, where ads are strictly regulated. In this case there was a higher prescription rate in the US than in Canada as people were more likely to ask their doctor to prescribe it for them.

A significant problem I have with the media response to this study is that the population investigated had familial hypercholesterolemia, which is a rare genetic disorder and likely with heterozygotes as homzygotes with this disorder are immune to drug treatment (although this was never stated in the article). So making a comparison to the wider population is somewhat misguided as the majority of the population does not have this genetic disorder. This demonstrates a significant disconnect between what is presented by the scientist, how it is interpreted in the media, and it is presented to the public. While I believe statins are over-prescribed (like antibiotics) and we will end up facing consequences of a dire magnitude (similar to anti-biotic resistance) and an increase in cardiovascular diseases in the near future this particular case is far fetched. It would be better to look at a Ezetimbibe study of a general population but this won't be available until 2011.

Heart Disease and the Oldest Old

This is an interesting article from the Archives of Internal Medicine on heart disease and elderly people. They suggest the results are surprising as heart disease is a disease of age and when we get older it should increase in incidence. What they find is that while heart disease does increases in individuals from 65-69 it drops dramatically when in an age cohort that includes individuals 85 and older (~10 %). I actually don't find these results all that astonishing as there appears to be an important shift in what the medical community uses as traditional risk factors for heart disease as individual transitions from middle age into being elderly (whatever that means). This would appear to be mirrored in these data as well.

I enjoy articles like this because they make us confront a whole host of issues that are going to become important over the next two decades. As I've mentioned before the fastest growing non-immigrant segment of US is those 85 and older (referred to as the oldest old). The problem is we really don't understand the underlying physiology of this transition and its implications for social policy and public health.

Incidence and Prevalence of Heart Failure in Elderly Persons, 1994-2003

Lesley H. Curtis, PhD; David J. Whellan, MD, MHS; Bradley G. Hammill, MS; Adrian F. Hernandez, MD, MHS; Kevin J. Anstrom, PhD; Alisa M. Shea, MPH; Kevin A. Schulman, MD

Background Recent analyses have presented conflicting evidence regarding the incidence and prevalence of heart failure in the United States. We sought to estimate the annual incidence and prevalence of heart failure and associated survival in elderly persons from January 1, 1994, through December 31, 2003.

Methods We conducted a retrospective cohort study of 622 789 Medicare beneficiaries 65 years or older who were diagnosed as having heart failure between 1994 and 2003. The main outcome measures were incidence and prevalence of heart failure and survival following a heart failure diagnosis.

Results The incidence of heart failure declined from 32 per 1000 person-years in 1994 to 29 per 1000 person-years in 2003 (P < .01). Incidence declined most sharply among beneficiaries aged 80 to 84 years (from 57.5 to 48.4 per 1000 person-years, P < .01) and increased slightly among beneficiaries aged 65 to 69 years (from 17.5 to 19.3 per 1000 person-years, P < .01). Although risk-adjusted mortality declined slightly from 1994 to 2003, the prognosis for patients diagnosed as having heart failure remains poor. In 2002, risk-adjusted 1-year mortality was 27.5%, more than 3 times higher than for age- and sex-matched patients.

Conclusions Although the incidence of heart failure has declined somewhat during the past decade, modest survival gains have resulted in an increase in the number of patients living with heart failure. Identifying optimal strategies for the treatment and management of heart failure will become increasingly important as the size of the Medicare population grows.

Low Maternal Cholesterol Tied To Premature Birth

I don't like too harp on the cholesterol thing too much but a number of studies are demonstrating that low cholesterol may be just as bad as high cholesterol. I firmly believe that the body has a threshold for cholesterol levels and too high and too low are both bad with one leading to heart disease and the other cancer as well. Science Daily has an interesting article (available here) of the impact of low cholesterol and premature babies. I like this quote from the article

"The right amount of cholesterol is fundamental for good health, both before and after birth," explained Dr. Muenke. "During pregnancy, cholesterol is critical for both the placenta and the developing baby, including the brain."

US Health 2006

On Sunday Yahoo news had an article on Life Expectancy in the US and how we have slipped from 11th to 42nd on the list over the last 20 years. While 77.9 years is a record I became curious as to what the other countries in the list were and I came across the CDC National Health Statistics for 2006 (can be accessed here). This is a data heavy report, while light on the analytical side, it has a number of interesting highlights. Below are some of those ones I found interesting.

1) Large disparities in infant mortality rates among racial and ethnic groups continue to exist. In 2003, infant mortality rates were highest for infants of non-Hispanic black mothers (13.6 deaths per 1,000 live births), American Indian mothers (8.7 per 1,000), and Puerto Rican mothers (8.2 per 1,000); and lowest for infants of Cuban mothers (4.6 per 1,000 live births) and Asian or Pacific Islander mothers (4.8 per 1,000) (Table 19).

(2) From 1950 to 2005, the total resident population of the United States increased from 151 million to 296 million, representing an average annual growth rate of 1.2% (Figure 1). During the same period, the population 65 years of age and over grew on average 2.0% per year, increasing from 12 to 37 million persons. The population 75 years of age and over grew the fastest (on average, 2.8% per year),increasing from 4 to 18 million persons.

Projections indicate that the rate of growth for the total population from now to 2050 will be slower, but older age groups will continue to grow more rapidly than the total population (1). By 2029, all of the baby boomers (those born in the post World War II period 1946–1964) will be age 65 years and over. As a result, the population age 65–74 years will increase from 6% to 10% of the total population between 2005 and 2030 (data table for Figure 1). As the baby boomers age, the population 75 years and over will also rise from 6% to 9% of the population by 2030 and continue to grow to 12% in 2050. By 2040 the population age 75 years and over will exceed the population 65–74 years of age.

(3) In 2004, the United States spent 16% (up from 14% in 2000) of its Gross Domestic Product (GDP) on health care, a greater share than any other developed country for which data are collected by the Organisation of Economic Co-operation and Development (Figure 8 and Tables 119 and 120).

(4) In 2003, the age-adjusted death rate for heart disease, the leading cause of death, was 60% lower than the rate in 1950 (Table 36). The age-adjusted death rate for stroke, the third leading cause of death, declined 70% since 1950 (Table 37).Heart disease and stroke mortality are associated with risk factors such as high cholesterol, high blood pressure, smoking, and dietary factors. Other important factors include socioeconomic status, obesity, and physical inactivity. Factors contributing to the decline in heart disease and stroke mortality include better control of risk factors, improved access to early detection, and better treatment and care, including new drugs and expanded uses for existing drugs (1).

(5) In 2003, 96% of persons 65 years of age and over in the civilian noninstitutionalized population reported medical expenses that averaged about $8,210 per person with expense. Nineteen percent of expenses were paid out-of-pocket, 16% by private insurance, and 63% by public programs (primarily Medicare and Medicaid) (Tables 125 and 126).

Just a few facts to chew on.