Any doctor worth his salt recognizes that patients don’t always respond the way we anticipate they will. For example, utilizing the best of our scientific methodologies we know LDL is causally related to vascular disease. High LDL causes disease while low LDL mitigates it. Yet, we occasionally see patients with extraordinarily high LDL and no disease, as well as those with very low LDL and severe disease. In some circumstances, patients with a vascular disease promoting mutation – as in Familial Hypercholesterolemia – will have severe and premature heart disease while their relatives with the same mutation somehow remain unscathed. How can this be? What we’ve all come to believe is that there must be protective genes that somehow offset the detrimental aspects of other genes. Let’s dub these desired genes “Guardian Genes”.
In the case of vascular disease promoting disorders, Guardian genes cause the exception, not the rule. They Teflon coat individuals who under normal circumstances should develop heart attacks and strokes. This wonderful rarity can unfortunately lead to a misunderstanding of disease processes as well as their cures. When someone speaks of grandma whose LDL was 300 and yet lived to the ripe old age of 100, sans MI or stroke, the take-home message often is, “Those doctors don’t know what they’re talking about. LDL is not the cause of heart disease. My LDL is only 200 and as grandma lived to 100 and with worse numbers, why should I take that statin medicine. Just look at the Internet and you can see how terrible those medicines are.” Unfortunately the Guardian genes are currently merely speculative. As such we cannot identify them. And, we know that intra-family variability in development of vascular disease supports the notion that theses guardian genes are inherited entirely separately from the disease promoting genes. What that means is just because grandma won the lottery, don’t bet your life (literally) that you did as well. In my own practice I’ve seen 70-year-old parents mourn the deaths of their 40-year-old sons and daughters who died of MIs. Though they shared the same bad genes, the parents did not suffer the unfortunate (and more predictable fate) of their children.
The bottom line here is that we doctors must base our treatment recommendations on the odds. We weigh and measure the pros and cons of therapeutic options (like the statins) against the likelihood that an individual patient will develop a serious event such as a heart attack, stroke, or even death. We use our best judgment based upon many facets of knowledge and understanding. We then make our recommendations hoping to stave off future adverse cardiovascular events. We never risk a patient’s life hoping he or she has inherited a guardian gene. Until we identify the elusive lifesaver guardian genes they will remain relegated to being the modern day Holy Grail of genetics. We all pray we will find them, but until that day we must continue to practice within the limits of our understanding. And while we do, we hope our patients understand that our suggestions and recommendations are born of both a deep understanding of the science of medicine and the burning desire to help our patients live the longest and best lives possible.