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Introducing Allergy Shots at Home

Studies as early as the 1960s suggested that measurement of HDL-C subclasses might add information in CHD risk prediction. 23 Consistent with our findings, multiple studies have found that higher HDL 3 -C is most strongly associated with lower risk. 12–14 However, other studies showed the opposite 10 , 11 and, by extension, suggested that HDL 2 is the more protective subclass. Working towards resolution of this subclass controversy is ever more important given the demonstration in our study and other contemporary secondary prevention studies 7 , 8 that total HDL-C levels are not predictive of risk combined with difficulties in developing therapies targeting total HDL-C levels. 24 , 25 The results of this study, along with parallel primary prevention analyses using the same methodology for HDL-C subclassification (manuscript submitted jointly), tip the balance of evidence to HDL 3 -C as the primary mediator or marker of risk ( Supplementary material online, Table S8 ).

Mortality is an objective endpoint but subject to competing non-cardiovascular risks. Our data suggest that the relationship of HDL 3 -C levels with mortality in CHD patients may be modestly U-shaped. This is compatible with findings from the Livermore Cohort wherein the lowest HDL 3 quartile was associated with shorter longevity, while linear increases in HDL 3 were not. 26 A U-shaped relationship between HDL-C and mortality has also been described in several prior studies. 27–29 In a Veterans Administration Medical Center Population with low LDL-C, investigators observed a U-shaped relationship between HDL-C and 1-year all-cause mortality in unadjusted and adjusted analyses. 27

This observation might in part reflect the disconnect between HDL-C levels and HDL function and might also reflect HDL as a marker for non-cardiovascular conditions that lead to mortality, such as diseases or accidents related to alcohol abuse. Nevertheless, adjustment for alcohol use failed to fully account for the weak U-shaped relationship in our study, as was also the case in the aforementioned Veterans Administration population. 27 This leaves open the possible role of dysfunctional HDL 30 or other mechanistic possibilities that are not yet well characterized. Transformation of HDLs to dysfunctional, pro-inflammatory forms appears to be an important determinant of cardiovascular risk, and more work is needed in this novel area of research. 30

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The state of work and employment is shifting, rapidly. Unemployment is low, yet the U.S. is faced with a crisis of mismatched skills, where automation, robotics, and technology in general are dramatically changing the needs of the workplace.

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