Unveiling the Hidden Enemy: Small, Dense LDL and Heart Disease
Since we first speculated that cholesterol was the root cause of heart disease, we have obsessed about nuking it out of existence, essentially with weapons-grade pharmaceuticals. Yet afflictions of the heart remain the number one cause of death in the Western world and we are no closer to claiming victory over an enemy that is eminently conquerable. This is because we are continuing to drive our troops down the wrong arterial thoroughfare. The primary cause of heart disease is not cholesterol. It’s not even LDL (low-density lipoprotein), long identified as the so-called “bad cholesterol”, the principal target of medications especially designed to reduce it to rubble.
It’s actually small, dense LDL, a much more pernicious form of LDL that is beyond the purview of these pharmaceuticals, and hence it continues to maintain its reign of terror, claiming the lives of so many who remained blissfully unaware that it was the central cause of their demise.
Since most of us don’t know about it we’re not measuring it, and as physicians remain wedded to the old lowering cholesterol/LDL paradigm we
are losing a battle we could so easily be winning. And yet there is a blood panel which quantifies small, dense LDL, and it goes by the name of the lipid subfractions test. It’s simply not being requested, mostly because doctors are unaware of its existence, which might in part be because we’ve yet to devise any drugs that effectively home in on its presence. What are the origins of small, dense LDL and how does it trigger the assembly of a malicious fatty sludge that puts a chokehold on our blood vessels?
Dissecting small, dense LDL
We’ve predominantly got the obesity epidemic to thank for the genesis of our predicament. The more fat we accumulate on the outside the more we deposit this malevolent residue on the inside of our bodies, especially around our livers where a flotilla of molecules overflowing with fat gathers en masse. From there it doesn’t require much metabolic activity to chop these fatty hunks into much smaller and easily transportable particles that are prime candidates for the formation of atheromatous plaques, the lethal blockage of our arteries leading to heart disease and mass casualties.
Small, dense LDL can effortlessly burrow into the walls of our blood vessels where they are engulfed by other hostile actors, this combination forming a potentially volatile fireball that is just waiting to erupt. What makes this incendiary cocktail more combustible is the presence of inflammatory molecules that are readily present in those suffering from diseases like rheumatoid arthritis, psoriasis, inflammatory bowel disease and ankylosing spondylitis. Along with inflammation, determined by means of a blood test which measures HS-CRP levels, oxidation or the build-up of free radicals can provide the kindling for a raging inferno. These free radicals multiply when your antioxidant defences are diminished and you are exposed to heavy metals like lead, mercury and aluminium or an excess of iron in your bloodstream, as well as pesticides and herbicides swamping your foods.
Genetics also play their part, and although it’s not commercially available yet, genetic testing will ultimately allow us to identify those who are at greater risk.
Aside from men being their own worst enemies with burgeoning waistlines not causing the alarm they should, overweight and obese children have an increased proclivity for having small, dense LDL surging through their bloodstreams. This makes children vulnerable to the early seeding of a lethal process that tragically might significantly truncate their life expectancy.
Underactive thyroid hormones, and even subclinical hypothyroidism when thyroid hormone levels are normal but levels of thyroid-stimulating hormone which are only modestly elevated, are associated with raised small, dense LDL, even when regulation cholesterol panels are within the reference range.
Then, without being pejorative in any way, women who suffer from polycystic ovarian syndrome, a disorder associated with weight gain, raised blood sugar levels and inflammation can be a fertile ground for this cardiovascular quagmire as can pregnancy and menopause, when a decline in the hormone oestrogen makes it easier for small, dense LDL to proliferate.
Combatting small, dense LDL
Realising the gravity of our plight, research scientists and the pharmaceutical industry have devised medications called PCSK9 inhibitors which target small, dense LDL, but in a recent clinical review these were not found to reduce the risk of heart attacks or strokes, and one of the drugs called evolocumab was found to increase the risk of mortality.
At the moment, we’re way behind the eight ball when it comes to preventing heart disease, partly due to our destructive lifestyles compounded by our ignorance of the primary culprit that we need to identify with appropriate medical investigations and manage with individualised interventions.
I have one patient who reduced her small, dense LDL to zero by eliminating butter and limiting her fat consumption to the occasional dollop of yoghurt. While we all need some fat, it’s the kind of extreme evasive action we must embrace if we are going to beat this thing.