Debra A. Heller

Genetic and Environmental Influences on Serum Lipid Levels in Twins

BACKGROUND The extent to which serum lipid levels are affected by genetic and environmental factors remains a point of controversy. We examined both genetic and environmental influences on serum lipid levels in twins reared either together or apart who participated in the Swedish Adoption/Twin Study of Aging. METHODS We studied 302 pairs of twins (mean age, 65.6 years; range, 52 to 86); 146 pairs had been reared apart. We simultaneously compared the twins on the basis of both zygosity and rearing status, which allowed joint estimation of genetic and environmental influences on serum lipid levels. Genetic influence was expressed in terms of heritability, the proportion of the population variation attributable to genetic variation (a value of 1.0 indicates that all of the population variation is attributable to genetic variation). The serum lipids and apolipoproteins measured included total cholesterol, high-density lipoprotein cholesterol, apolipoproteins A-I and B, and triglycerides. RESULTS Structural-equation analyses revealed substantial heritability for the serum levels of each lipid measured, ranging from 0.28 to 0.78. Comparisons of the twins reared together with those reared apart suggested that the environment of rearing had a substantial impact on the level of total cholesterol (accounting for 0.15 to 0.36 of the total variance). Sharing the same environment appeared to affect the other lipid measures much less, however, than did genetic factors and unique environmental factors not shared by twins. Comparisons of younger with older twins suggested that heritability for apolipoprotein B and triglyceride levels decreased with age. CONCLUSIONS The effect of genetic factors on the serum levels of some but not all lipids appears to decrease with age. Early rearing environment appears to remain an important factor in relation to levels of total cholesterol later in life, but it has less effect on other serum lipids and apolipoproteins in the elderly.

Health-related quality of life among older adults with arthritis

BackgroundHealth-related quality of life (HRQOL) is a key outcome in arthritis, but few population-based studies have examined the relationship of specific arthritic conditions, such as osteoarthritis (OA) and rheumatoid arthritis (RA) with HRQOL.MethodsOlder adults in Pennsylvania completed a mail version of the Centers for Disease Control and Prevention (CDC) HRQOL modules. Medicare data were used to identify subjects with OA, RA, and no arthritis diagnosis. We compared HRQOL responses among these groups, and we also examined relationships of demographic characteristics to HRQOL among subjects with arthritis.ResultsIn analyses controlling for demographic characteristics and comorbidity, subjects with OA and RA had poorer scores than those without arthritis on all HRQOL items, including general health, physical health, mental health, activity limitation, pain, sleep, and feeling healthy and full of energy. HRQOL scores were also lower for those with RA compared to OA. Among individuals with arthritis, all subject characteristics (including age, race, sex, nursing home residence, marital status, income, and comorbid illnesses) were significantly related to at least one HRQOL item. Older age, nursing home residence, and greater comorbidity were the most consistently associated with poorer HRQOL.ConclusionsResults of this study show that both OA and RA have a significant impact on multiple dimensions of HRQOL among older adults. Results also suggest the CDC HRQOL items are suitable for use among older adults and in mail surveys. Due to the rising number of older adults in many countries, the public health burden of arthritis is expected to increase dramatically. Efforts are needed to enhance access to medical care and disseminate self-management interventions for arthritis.

Genetic and environmental influences on blood pressure in elderly twins.

We used 289 pairs of Swedish twins reared apart or together to evaluate the importance of genetic and environmental influences on blood pressure. Unlike other twin and family studies, the adoption/twin design allows a distinction between estimates of the importance of shared rearing environments and genetic effects. Genetic factors were observed to play an important role for individual differences in blood pressure. Model-fitting analyses suggested upper limits of heritability for systolic and diastolic blood pressures in the entire sample of 0.44 and 0.34, respectively. More interestingly, substantial influences of shared family effects accounting for up to 27% of the variation were also revealed. Effects of correlated environment, which might reflect, for example, the intrauterine environment, existed to some extent later in life. The influence of genetic factors tended to decrease across age groups for systolic blood pressure (0.62 in individuals less than 65 years old; 0.12 in those 65 years and older) but not for diastolic blood pressure (0.22 for the middle-aged group; 0.26 for the older group). However, this declining trend for systolic blood pressure did not reach significance (chi 2 = 8.07, df = 4, P = .09).

Among older adults, the responsiveness of self-rated health to changes in Charlson comorbidity was moderated by age and baseline comorbidity

OBJECTIVE To examine the impact of changes in comorbidity--as measured by the Charlson comorbidity index--on self-rated health in a large sample of community-dwelling elderly over a 1-year period, and to examine the differential effects of changes in specific Charlson diagnostic categories. STUDY DESIGN AND SETTING Longitudinal survey data on self-rated health were linked with Medicare inpatient, outpatient, and physician visit data for 30,535 U.S. elderly residing in Pennsylvania. Multivariate logistic regression with fractional polynomials was used to model relationships involving baseline and changing Charlson comorbidity with self-rated health decline, and to evaluate covariate interactions. RESULTS Comorbidity change was associated with greater likelihood of worsened self-rated health, but the relationship was nonlinear and was moderated by age and baseline comorbidity. The impact of comorbidity change appeared to be less among older individuals and those with higher baseline comorbidity. Declines in self-rated health were most likely following new diagnoses for metastatic tumors, paralysis, and dementia. CONCLUSION Self-rated health is responsive to changes in Charlson comorbidity, but nonlinearity and interactions suggest complexity in how elderly respond to comorbidity change. Younger individuals and those with initially low comorbidity are more likely to reduce self-ratings of health following new diagnoses for chronic conditions.

Potential environmental effects on adult lipoprotein(a) levels: results from Swedish twins

Two hundred and ninety four pairs of Swedish twins reared apart and twins reared together were used to evaluate the importance of genetic and environmental influences on lipoprotein(a) (Lp(a)) levels. Lp(a) levels ranged from <10 mg/l to 926 mg/l with 7.9% of the sample having undetectable Lp(a) levels (i.e. <10 mg/l). A substantial genetic component in Lp(a) variation was indicated by a heritability estimate of approximately 90%. No difference in heritability was found across age groups. Quantitative genetic analyses also suggest correlated environmental effects most likely composed of maternal, neonatal and postnatal environmental influences. However, these effects did not reach statistical significance, partly due to a lack of power. Results from analyses of co-twin differences in Lp(a) levels for monozygotic twins indicate that sex hormone use may be of importance for Lp(a) variation in women. There was no evidence of potential influences of alcohol consumption, beta-blocker and diuretic administration on Lp(a) levels in either men or women.

Dehydration in black and white older adults using diuretics.

PURPOSE To assess the association between dehydration and ethnicity in older adults; and to determine if diuretic use can help explain the disparity between blacks and whites in diagnosis of dehydration. METHODS We conducted a case-control study in black and white older adults in a pharmaceutical assistance program who were hospitalized during 1997. Cases were all those diagnosed with dehydration (N=9186). Randomly selected controls were 4:1 frequency matched to cases by sex and age group (N(Total)=45585). RESULTS Patients taking loop, potassium-sparing, thiazide or combination diuretics were more likely to have a diagnosis of dehydration. Dehydration diagnosis was associated with being black (odds ratio (OR)=1.49, 95% confidence interval (CI), 1.36-1.63, p<.001), independent of diuretic use or dosage. That association remained when examining loop (OR=1.36, 95% CI, 1.10-1.63, p<.004) and thiazide diuretic users (OR=1.59, 95% CI, 1.09-2.34, p=.017), but not potassium-sparing or combination diuretic users. CONCLUSION Diuretic use is significantly associated with dehydration diagnosis, but the greater likelihood of older blacks being diagnosed with dehydration is independent of diuretic use. The increased risk of morbidity and mortality associated with dehydration suggests that further examination of the root cause of this disparity in risk is warranted.

The role of medication use and health on the decision to quit drinking among older adults.

Objectives: To determine the extent to which changes in medication use and health influence the decision to quit drinking among older adults. Method: The sample consisted of 8,883 elderly enrolled in Pennsylvanias Pharmaceutical Assistance Contract for the Elderly (PA-PACE) program who completed surveys in 2000 and 2002. Survey data were linked with prescription claims to examine medication and health factors associated with drinking cessation between baseline and follow-up. Results: Overall, 3.9% of those using alcohol at baseline quit drinking during the study period. Logistic regression results showed that individuals who initiated antipsychotic (OR = 2.92) and antineoplastic therapies (OR = 2.67) were the most likely to quit drinking. Discussion: These findings support the hypothesis that elderly quit drinking in response to ill health. Results have implications for alcohol interventions in older adults and underscore the importance of separating former drinkers from lifetime abstainers in the study of alcohol-health relationships.

Individual variability in tail tendon fiber break time in three age cohorts of ifferent strains of mice

Individual variability in mouse tail tendon fiber denaturation in urea was investigated. Differences in break time between fibers within tendons and between tendon groups were examined. Mean break times for each strain increased with age with the shorter-lived DBA/2 mice exhibiting higher break times within age cohorts than the C57BL/6 animals. Fibers from the two ventral tendon groups had consistently higher break times than those from the two dorsal groups, implying differential rates of collagen maturation between these two areas within the tail. Histological examination revealed conspicuous morphological dorsal/ventral differences in tendon number, proximity to a major blood vessel, and the amount of surrounding muscle tissue. These findings have methodological and experimental design implications for the use of tail tendon break time (TTBT) as a biomarker of aging. Furthermore, they suggest possible physiological mechanisms for differential rates of collagen aging.

GENDER, AGING, AND QUALITY OF LIFE

One of the most striking demographic aspects of aging in developed nations is the sex difference in longevity and in age-related disease. Understanding the determinants of this phenomenon might powerfully illuminate basic aspects of aging processes and provide for the design of rational interventions.