A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly

Abstract

High density lipoprotein cholesterol (HDL-C) levels are inversely associated with the incidence of coronary heart disease (CHD) in middle-aged individuals; in the elderly, the association is less clear. Genetic factors, including variations in the cholesteryl ester transfer protein (CETP) gene, play a role in determining HDL-C levels. Controversy remains about whether CETP deficiency and the resultant rise in HDL-C are antiatherogenic, or whether CETP has the opposite effect due to its role in reverse cholesterol transport. In a seven-year follow-up of 2,340 men aged 71-93 in the Honolulu Heart Program, the age-adjusted CHD incidence rates were significantly lower in men with high versus low HDL-C levels. After adjustment for age, hypertension, smoking, and total cholesterol, the relative risk of CHD for those with HDL-C levels у 60 mg/dl, compared with those with HDL-C levels Ͻ 40 mg/dl, was 0.6. Men with a CETP mutation had the lowest rates of CHD, although this was not statistically significant. These data indicate that HDL-C remains an important risk factor for CHD in the elderly. Whether a CETP mutation offers additional protection against CHD warrants further investigation.

The Relationship between Very High Levels of Serum High-Density Lipoprotein Cholesterol and Cause-Specific Mortality in a 20-Year Follow-Up Study of Japanese General Population

“…Furthermore, the high HDL-C category (1.56 -2.06 mmol/L) showed significant inverse association with CHD mortality; however, the very high HDL-C category ( ≥ 2.07 mmol/L) did not show significant relationship with CHD. Consequently, there is no inverse relationship between HDL-C levels and cardiovascular mortality because major subtype of CVD in Japan is stroke 13,23) ; in fact, the proportion of stroke within CVD (39%) was twice as large as that of CHD (21%) in the present study.…”

“…As mentioned above, in Japan, stroke mortality is much higher than CHD mortality 13,23) , and to our knowledge, almost all Japanese cohort studies did not show any positive relationship between TC or LDL-C and cerebral infarction 24,25) . Even in a large worldwide pooled analysis 26) , a weak positive relationship between TC or LDL-C and stroke was only observed.…”

“…Model 2: adjusted for age bmi triglyceride (log-transformed) non-hdl hypertension diabetes smoking drinking ( sex ) very high HDL-C levels prevent CHD. It has been reported that high levels of serum HDL-C per se protect against CHD regardless of the cause of HDL-C elevation when high HDL-C was defined as ≥ 1.56 mmol/L 13,21) . In contrast, pooled analysis of six cohort studies has shown that very high HDL-C defined as ≥ 2.07 mmol/L increased the risk for CHD events 28) .…”

“…To date, there are no communitybased cohort studies concerning the relationship between very high serum levels of HDL-C and CHD or cause-specific mortality. It is very difficult to set a very high HDL-C group in a cohort study 13) . Although our previous study tried to examine the relationship between very high HDL-C levels and causespecific mortality 14) , we did not set a very high HDL-C group because of small number of events.…”

Dysfunctional high-density lipoproteins in coronary heart disease: implications for diagnostics and therapy

“…Investigations of both monogenic CETP deficiency and polymorphisms in the CETP gene provided controversial evidence. Some studies reported reduced cardiovascular disease risk and prolonged life expectancy in individuals with CETP mutants, [193][194][195][196] others did not find any impact or even increased cardiovascular risk. 197,198 Previous meta-analyses of genetic studies, provided compelling evidence that polymorphisms that are associated with reduced CETP activity and increased HDL-cholesterol levels are also associated with reduced cardiovascular risk.…”