To the surprise of researchers who had thought the very notion a joke, an international consortium of investigators reported on Wednesday that shorter stature increases the risk of heart disease. 
 
 After gathering genetic data from nearly 200,000 men and women worldwide, the investigators found that each extra 2.5 inches of height brings a 13.5 percent reduction in heart disease risk. The relationship is present throughout the range of adult heights. 
 
 A person who is five feet tall has a 30 percent greater chance of developing heart disease than someone who is 5 feet 6, said a lead author of the new study, Sir Nilesh Samani, a professor of cardiology at the University of Leicester in England. 
 
 Of course, the increased risk pales in comparison to that caused by smoking, which elevates the odds of getting heart disease by 200 to 300 percent. 
 
 There is nothing people can do about their height, but the researchers hope the finding will lead to the discovery of new links to heart disease. The paper was published in The New England Journal of Medicine. 
 
 No one was more surprised by the result than heart disease experts, although they have known about a purported association between height and heart disease for more than half a century. It was first pointed out in 1951 by Dr. Paul Dudley White, a cardiologist who was President Dwight D. Eisenhower’s physician. 
 
 He observed that 97 men and three women who had a heart attack before age 40 and were admitted to Massachusetts General Hospital were two inches shorter on average than 146 healthy men. 
 
 Since then, experts have noted that shorter people are more likely to get heart disease in a variety of populations and ethnic groups, even after accounting for such risk factors as smoking and cholesterol, diabetes and obesity. But few researchers took the finding seriously. 
 
 Height was just a marker for some other problem causing heart disease, most scientists said — perhaps a poor diet, or infectious diseases in childhood that led to a lifelong weakness of the heart. 
 
 “This idea that shorter stature is associated with coronary artery disease is something we would laugh about,” said Dr. Michael Lauer, director of cardiovascular sciences at the National Heart, Lung and Blood Institute. “We would think about it as yet another example of epidemiology going amok.” 
 
 Dr. Samani and his colleagues realized that if there was a real link, genetic variations that resulted in short stature would also result in a greater risk of heart disease. 
 
 Previous research had identified 180 genetic variants that control height. To find out if those variants also affected heart disease risk, Dr. Samani and his colleagues examined the genetic profiles of more than 200,000 people whose DNA had been analyzed in a variety of other studies. 
 
 People with the genetic variants were more prone to heart disease, the scientists found. But what was the connection? Did the genes controlling height also affect obesity, diabetes or blood pressure? 
 
 Dr. Samani and his colleagues found just one link, and it was a very small one: The genetic variants associated with shorter stature also were linked to slightly higher levels of LDL, the form of cholesterol that increases heart disease risk, and to slightly higher levels of triglycerides, blood fats that are also a risk. 
 
 But that was not enough to account for all of the increased risk, noted Dr. Sekar Kathiresan, an author of the paper and director of preventive cardiology at Massachusetts General Hospital. The rest, the researchers speculated, may come from poorly understood mechanisms, governed by height genes, that control the development of both blood vessels and bones. 
 
 Not everyone is impressed by the new report. Dr. Kari Stefansson, chief executive of deCODE Genetics, said the increase in heart disease risk was real but so small as to be not very meaningful. “It’s a weak effect,” he said. 
 
 Others, like Dr. Lauer, find the new report an exciting taste of the science to come. Until recently, heart disease research focused on factors that greatly increase risk, like cholesterol levels. Research into the genetic underpinnings of disease may point to more “low-hanging fruit” in “other orchards we haven’t seen,” Dr. Lauer said. 
 
 Studies of huge DNA databases, like the new research, show the power of genetics to resolve questions that had seemed unanswerable. 
 
 “The Achilles’ heel of epidemiology has been the inability to distinguish between associations that are correlations and those that are causal,” Dr. Lauer said. Until now, the only way to do that was through large, expensive and time-consuming randomized controlled clinical trials. 
 
 For example, the Women’s Health Initiative studied whether taking hormones after menopause could reduce the risk of heart disease, which seemed well established. Thousands of women were told to take hormones after menopause, or not to. After years of study and millions of dollars, the result was clear: The hormones did not protect against heart disease. 
 
 Of course, no randomized trial can test whether height is linked to heart disease risk. But genetic variations are distributed at random in populations, and genes are not affected by lifestyle or environmental factors that have to be accounted for when researchers analyze data they get by simply observing populations. 
 
 In a sense, Dr. Lauer said, we are nature’s random experiments. ||||| Short people are more likely to develop coronary heart disease with the risk increasing by 13 per cent for every 2.5 inches smaller they are, the University of Leicester has found. 
 
 It means that compared with a 5ft 6inch tall person, a 5ft tall person on average has a 32 per cent higher risk of coronary heart disease because of their relatively shorter stature. 
 
 It is the first time that scientists have shown that height alone is enough to raise the risk. 
 
 “We have shown that the association between shorter height and higher risk of coronary heart disease is a primary relationship and is not due to confounding factors such as nutrition or poor socioeconomic conditions,”said Professor Sir Nilesh Samani, BHF Professor of Cardiology at the University of Leicester. 
 
 Coronary heart disease is the most common cause of death in Britain, killing around 73,000 people each year. There are 2.3 million people currently living with the condition. 
 
 It occurs when the arteries that supply blood to the heart muscle become narrowed due to a deposition of fatty material in the walls of the arteries. 
 
 If a blood clot forms over the plaque then the artery can become completely blocked suddenly giving rise to a heart attack. 
 
 The researchers looked at genetic data from 200,000 people and found that those parts of the DNA which determined height could be correlated to the chance of developing coronary heart disease. 
 
 “The more height increasing genetic variants that you carry the lower your risk of coronary heart disease and conversely if you were genetically shorter the higher your risk,” said Dr Christopher Nelson, a researcher and lecturer from the University of Leicester. 
 
 Professor Samani added: “While we know about many lifestyle factors such as smoking that affect risk of coronary heart disease, our findings underscore the fact that the causes of this common disease are very complex and other things that we understand much more poorly have a significant impact. 
 
 “While our findings do not have any immediate clinical implications, better and fuller understanding of the biological mechanisms that underlie the relationship between shorter height and higher risk of coronary heart disease may open up new ways for its prevention and treatment.” 
 
 The research was published in the New England Journal of Medicine. ||||| Your Health 
 
 Link Between Heart Disease And Height Hidden In Our Genes 
 
 i itoggle caption PW Illustration/Ikon Images/Corbis PW Illustration/Ikon Images/Corbis 
 
 Shorter people are more likely than taller folks to have clogged heart arteries, and a new study says part of the reason lies in the genes. 
 
 Doctors have known since the 1950s about the link between short stature and coronary artery disease, "but the reason behind this really hasn't been completely clear," says Nilesh Samani, a cardiologist at the University of Leicester in the U.K. 
 
 One thought was that smaller people have smaller arteries, which are easier to clog. Another possibility is that short stature can be a result of poor nutrition and health while growing up, and that could also be linked to health problems later in life. 
 
 Samani and a large group of colleagues decided to find out about the role genes play in the link between height and coronary heart disease. Previous studies have identified 180 spots in the genome that can vary, depending on whether a person is short or tall. So Samani's group decided to see whether people with genetic traits for short stature also had a higher risk for coronary artery disease. (All together these genetic variations determine only 10 percent of your total height.) 
 
 Samani and his colleagues looked at the genes of nearly 200,000 people, "and we found a very striking relationship," Samani says. 
 
 For someone 2.5 inches shorter than average, the risk of coronary artery disease increases by about 13.5 percent. And the shorter you are, the larger the effect. But the risk is much smaller than the risk posed by smoking or high cholesterol. 
 
 The team didn't see a significant connection in women. This could be because the study had fewer women — about 80,000, compared to men. Or there may not be a genetic effect of height on coronary heart disease in women. 
 
 The findings were reported Wednesday in The New England Journal of Medicine. 
 
 Most of these height genes had no obvious connection to heart disease, though a few of them did, such as a trait related to LDL cholesterol and another that influences triglycerides. Those account for less than a third of the effect, leaving the root cause of this link mainly a mystery. 
 
 "We've been rather simplistic in our view of what causes coronary artery disease," Samani tells NPR. "We thought about traditional risk factors and then genes that might cause coronary disease. But what this [study] highlights for me is that probably developmental processes are going on that probably have an influence on height, and they probably also have an influence on [blood vessels of the heart] in a way that predisposes you to getting coronary artery disease." 
 
 The challenge now is to ferret out the actual genetic variations that underlie both height and heart disease. 
 
 "Eventually, of course, there may be some treatments that could emerge from this, but I wouldn't want to say that's a short-term possibility," Samani says. 
 
 One big shortcoming of the research is that the people studied were overwhelmingly white (all the samples were from Britain). David Goldstein, who directs the Institute for Genomic Medicine at Columbia University, says this racial inequity is a serious problem for many studies of this nature. 
 
 "We really do continue to see many more studies done in individuals of European ancestry, as opposed to other ancestry groups, and that is simply unfair," he says. 
 
 Goldstein says these studies should be more inclusive so everyone can benefit. For him, this study of height and heart disease is a reminder that science is on the edge of having a deeper understanding of many traits that matter most, like the ones that cause diseases and influence how long people live. 
 
 "As we begin to systematically characterize the genetic bases of these traits, it's going to open up a whole bunch of brand new windows into biology," Goldstein says. "And that's really what I find exciting." 
 
 The study of height and heart disease is also a reminder that traits are usually the result of many different genes acting in concert, so it's not so simple to alter these traits, for example, to treat or prevent disease. ||||| In this study, we found an association between a genetically determined decrease in height and an increased risk of CAD. Our finding validates the epidemiologic observation of an inverse association between height and CAD.1,2 
 
 Figure 3. Figure 3. Interpreting the Association between Genetically Determined Shorter Height and Increased Risk of CAD. The main advantage of the genetic approach is that it reduces the likelihood of known and unknown demographic, lifestyle, socioeconomic, or behavioral confounders that have an independent effect on height and the risk of CAD (solid black lines) and could give rise to a false association between the two factors. It is possible that the association between the studied genetic variants and height and the association with CAD are through completely different mechanisms (dashed black lines). However, the more likely scenario on the basis of our findings is that height variants affect biologic pathways, which on the one hand determine achieved height and on the other hand influence the risk of CAD (solid red lines). It is also possible that genetically determined height itself alters lifestyle or behavior, which then affects the risk of CAD (dashed red line). 
 
 A key advantage of using a genetic approach over a traditional epidemiologic approach to investigate an association such as that between height and CAD is that genotypes (because they are randomly distributed at birth) are unlikely to be confounded by lifestyle or environmental factors. Regardless of whether such factors are known (e.g., poor nutrition or socioeconomic conditions during childhood) or unknown, they can independently affect achieved height and the risk of CAD and lead to a spurious association between them (Figure 3). It is nonetheless possible that the genetic variants themselves affect height and CAD risk through entirely different mechanisms. However, given the large number of variants that we included in the analysis, all of which were selected only because of their association with height, it is likely that at least some of the processes are shared. This hypothesis is supported by the finding from the individual-level analysis of genetic risk score showing a direct correlation between the presence of an increasing number of height-related alleles and a reduction in the risk of CAD (Figure 2). 
 
 A genetic approach also offers novel methods to explore potential mechanisms linking shorter height with an increased risk of CAD (Figure 3). In this context, we performed two analyses. First, we applied the same genetic approach to investigate the association between height-related genetic variants and several established and potential cardiovascular risk factors. Notable negative findings here include the lack of an overall effect of height-associated SNPs on body-mass index. This suggests that the association between shorter stature and an increased risk of CAD is not mediated by an effect on obesity. On the other hand, there was a significant overall association between height SNPs and LDL cholesterol and triglycerides in a direction consistent with their association with CAD. The association between shorter stature and increased plasma LDL cholesterol and triglyceride levels has also been observed in epidemiologic studies.2 The mechanisms by which height-associated SNPs have an effect on LDL cholesterol and triglyceride levels are not clear. In any case, these effects in combination potentially explain less than one third of the observed association between genetically determined shorter height and an increased risk of CAD. 
 
 Second, we performed pathway analysis, which identified a number of overlapping pathways linking height-associated SNPs that could also have an effect on the risk of CAD, including the BMP- and TGF-β–signaling pathways, axon-guidance pathways, and the STAT3 and IGF-I pathways, all of which have experimentally documented roles in the development of atherosclerosis.21-26 The limitations of pathway analysis included the need to assign a specific gene for each height-associated locus and incomplete knowledge regarding how such pathways are constructed. (A fuller discussion of the pathways is provided in the Supplementary Appendix.) Taken together, these findings suggest that several overlapping and complex biologic pathways on the one hand influence development and height and on the other hand influence the risk of atherosclerosis through an effect on vascular biology and function (Figure 3). 
 
 In contrast to epidemiologic studies in which a similar inverse association between height and CAD was present in both men and women,2 we did not see a significant association in women. Whether this represents a genuine difference in the effect of genetically determined height on the risk of CAD between men and women or simply reflects the reduced power from the much smaller sample size available for analysis in women is unclear. Notably, the effect sizes that were observed in men and women were not significantly different in an interaction analysis. 
 
 Height and other measurements of body size have a positive correlation with the diameter of coronary arteries.27 Therefore, a potential simple explanation for an increased risk of CAD in shorter persons is that they have proportionally smaller-caliber coronary arteries, so a similar plaque burden could result in greater probability of symptomatic disease. However, women also have smaller-caliber arteries than men, independent of body size and height.27 Reduced height and female sex would therefore be expected to have an additive effect if this was the mechanism linking shorter height with an increased risk of CAD. In this context, the finding of a weaker association between genetically determined shorter height and CAD in women than in men would argue against a structural explanation on the basis of coronary-vessel caliber as the main explanation for the inverse association between height and CAD. 
 
 Although the genetic approach that we used allows us to reduce the possibility of confounding of any observed association by socioeconomic, lifestyle, or environmental factors, it does not rule out the possibility that the association between genetically determined shorter height with an increased risk of CAD is due to lifestyle choices or behavior adopted by such persons as a direct consequence of being shorter (Figure 3). Indeed, in an exemplar exploration of this possibility, we examined whether the height-related variants showed an association with the quantity of cigarettes smoked among smokers but found no evidence for this hypothesis (Table 1). Other relevant behavioral changes that could have an effect on the risk of CAD that could be adopted by persons of short stature include those related to diet, physical activity, and alcohol consumption. 
 
 In conclusion, using a genetic approach, we found an association between genetically determined shorter height and an increased risk of CAD. Part of this inverse association may be driven by the association between shorter height and an adverse lipid profile, although the majority of the relationship is likely to be determined by shared biologic processes that determine achieved height and atherosclerosis development. More generally, our findings underscore the complexity underlying the inherited component of CAD.
– It's tough enough being on the shorter side, and a new study in the New England Journal of Medicine doesn't make things any easier. Researchers in the UK find that being small of stature increases the risk of coronary heart disease, the Telegraph reports. More specifically, for every 2.5 inches shorter we are, our risk increases by 13.5%. In other words, a five-foot tall person has a 32% higher risk of heart disease than a five-foot-six person does. The findings, which involved data on 200,000 people, are tied to genetics; it seems the genes involved in height could also be involved in heart disease. "The more height-increasing genetic variants that you carry, the lower your risk of coronary heart disease—and conversely, if you were genetically shorter, the higher your risk," a researcher notes. That is, at least if you're a man, NPR reports: Researchers didn't discover a clear relationship between height and heart disease risk in women, though that might just be because the study involved more male than female subjects. Experts have been aware of an apparent relationship between height and heart disease since the 1950s without being able to explain it, NPR notes. In fact, the New York Times reports that researchers didn't take the idea that the two were linked very seriously, making these findings a surprise. "This idea that shorter stature is associated with coronary artery disease is something we would laugh about," notes one scientist. Another expert still has doubts, telling the Times that the connection appears "weak." And on the plus side for short men, a study last year found they live longer.