Should we rely on LDL alone to assess cardiovascular risk? (TG isn't convincingly associated with risk in Mendelian Randomisation either) Well, not if we have those other CVD risk factors, insulin resistance or type 2 diabetes.
Let’s walk this idea back to lipids and CVD. The TG/HDL ratio isn’t determined by your lipid genes, it’s a downstream effect of dietary carbohydrate (non-genetic) and insulin resistance (genes linked to IR and hyperglycaemia do correspond to CVD). The association between LDL and cardiovascular risk is modified by carbohydrate which increases TG-rich VLDL, the end product of which is the small, dense LDL particle, which is cleared more slowly than larger LDL particles and is thus exposed to peroxidation. Another effect of having a high output of TG-rich VLDL being that HDL gets loaded with TGs and is cleared from circulation faster (hence high TG, low HDL). Half of your LDL-associated risk can be traced to genes (like ApoE4) which you can try to tweak with drugs if you like, and half belongs to Beta-apolipoprotein, sdLDL, oxLDL etc, which are modified by the carbohydrate factor. Saturated fat effects on VLDL and LDL may differ depending on the foods they are in or the other macronutrients , especially carbohydrate.
|From Siri-Tarino et al 2015|
Your liver is downstream from your gut and has first pass at the nutrients you absorb there; its uptake of fats, sugars and proteins determines the triglycerides, cholesteryl esters, and apolipoptoteins the liver produces and its types of HDL and LDL species. Genetics has more influence on the LDL species than on the HDL or TG, and if you are insulin-resistant the effect of high-carbohydrate diet on HDL, TG-rich VLDL, and atherogenic LDL subspecies is magnified; this is the pathology that hyperlipidaemia, MetSyn, and diabetic lipid patterns have in common.
This is how Mendelian Randomization of LDL and HDL was presented in a recent butter and cholesterol paper [here]
“The LDL-cholesterol concentration is a true risk factor for CVD. A meta-analysis of 26 trials showed that, for every 1-mmol/L reduction in LDL cholesterol, there was a 20% relative reduction in deaths that were due to coronary heart disease (RR: 0.80; 99% CI: 0.74, 0.87) (30). Thus, our result of an increase in LDL-cholesterol concentration of 0.16 mmol/L was not negligible. In addition, butter resulted in a concomitant increase in HDL cholesterol compared with the habitual diet. An increase in HDL cholesterol of the butter diet rich in long-chain SFAs was expected because these SFAs are known to increase HDL cholesterol…
According to the literature, the HDL cholesterol concentration is associated with a protective effect on CVD (31, 32). However, studies that used Mendelian randomization showed that genetically decreased HDL cholesterol did not increase risk of myocardial infarction and questioned a causal association between the HDL concentration and CVD (33–35). Thus, it is necessary to be careful with interpreting low HDL-cholesterol concentrations as a CVD risk factor. However, as a marker of cardiovascular health, changes in HDL cholesterol concentrations need to be included when interpreting the effect of SFAs in the diet. It is possible to speculate that an unbeneficial increase in LDL cholesterol may partly be counteracted by the beneficial effect of SFAs on HDL cholesterol, which suggests that dairy and saturated fat may be less harmful in relation to CVD than previously thought, as reported in recent meta-analysis (8, 9).”Engel S and Thorstrup T (2015) Butter increased total and LDL cholesterol compared with olive oil however resulted in higher HDL cholesterol than habitual diet. Am J Clin Nutr. ajcn112227
Another suggestion is that HDL functionality is the important variable. HDL functionality is increased by CLA in butter and ruminant fat, olive oil polyphenols, and the action of vitamin E (found in nuts and vegetable oils and other sources of linoleic acid) on protein kinase-C. As substitution of all fats for carbohydrates tends to raise HDL, there will be a correspondence between intake of natural fats, HDL, and HDL functionality. Polyphenols administered without fat reduce inflammation but do not increase HDL or HDL functionality.
Thus there is evidence for a rather neat correspondence between the quality of dietary fat and the cardioprotection associated with HDL -
 Nicod N et al (2014) Green tea, cocoa, and red wine polyphenols moderately modulate intestinal inflammation and do not increase high-density lipoprotein (HDL) production. J Agric Food Chem. 2014 Mar 12;62(10):2228-32. doi: 10.1021/jf500348u. Epub 2014 Mar 4.
Holmes, MV, et al. Mendelian randomization of blood lipids for coronary heart disease. 2014. DOI: http://dx.doi.org/10.1093/eurheartj/eht571
But I'd putting money on this; these analyses don’t change the meanings of metabolic risk factors that are affected by diet and lifestyle, and if anything they support their usefulness as measures of improvement.