Paul E. Leaverton

Prevalence and mortality rate of congestive heart failure in the United States

OBJECTIVES The study was designed to determine the prevalence and mortality rate of congestive heart failure in noninstitutionalized men and women in the U.S. BACKGROUND Congestive heart failure is a serious condition with significant morbidity and mortality. Earlier epidemiologic descriptions of congestive heart failure were constructed from small surveys, limited data, hospital records or death certificates. No nationally representative data from noninstitutionalized persons have been examined. METHODS Data collected from the National Health and Nutrition Examination Survey (NHANES-I, 1971 to 1975) were used to determine the prevalence of heart failure on the basis of both self-reporting and a clinical definition. Mortality data were derived from the NHANES-I Epidemiologic Follow-up Study (1982 to 1986). RESULTS The prevalence of self-reported congestive heart failure approximates 1.1% of the noninstitutionalized U.S. adult population; the prevalence of congestive heart failure based on clinical criteria is 2%. These estimates suggest that between 1 and 2 million adults are affected. Mortality at 10 and 15 years for those persons with congestive heart failure increases in graded fashion with advancing age, with men more likely to die than women. In the group greater than or equal to 55 years old, the 15-year total mortality rate was 39.1% for women and 71.8% for men. CONCLUSIONS Congestive heart failure is a common problem in the U.S., with significant prevalence and mortality, both of which increase with advancing age. As the population of the U.S. becomes older, the health care impact of congestive heart failure will probably grow.

Representativeness of the Framingham risk model for coronary heart disease mortality: A comparison with a national cohort study

The Framingham Heart Study has been the foundation upon which several national policies regarding risk factors for coronary heart disease mortality are based. The NHANES I Epidemiologic Followup Study is the first national cohort study based upon a comprehensive medical examination of a probability sample of United States adults. The average follow-up time was 10 years. This study afforded an opportunity to evaluate the generalizability of the Framingham risk model, using systolic blood pressure, total cholesterol, and cigarette smoking, to the U.S. population with respect to predicting death from coronary heart disease. The Framingham model predicts remarkably well for this national sample. The major risk factors for coronary heart disease mortality described in previous Framingham analyses are applicable to the United States white adult population.

Drugs in the aetiology of agranulocytosis and aplastic anaemia

Abstract:  Agranulocytosis and aplastic anaemia are rare but serious conditions known to be caused by numerous drugs. Most of what is known or suspected about the aetiology is based on case reports, with only a few formal epidemiological studies that provide quantitative estimates of risk. Updated results have been obtained from a combined analysis of data from 3 case‐control studies that used similar methods: the International Agranulocytosis and Aplastic Anemia Study (IAAAS), conducted in Israel and Europe; a study conducted in the northeast US; and a study conducted in Thailand. Totals of 362 cases of agranulocytosis, 454 cases of aplastic anaemia and 6458 controls were included in the analyses. The IAAAS and Thai study were population‐based, providing estimates of the incidence of the 2 dyscrasias. The overall annual incidence of agranulocytosis in the ambulatory population was 3.4/106 in the IAAAS and 0.8/106 in Thailand; by contrast the incidence of aplastic anaemia was 2.0/106 in the IAAAS and 4.1/106 in Thailand. A total of 21 compounds were significantly associated with an increased risk of agranulocytosis in the IAAAS and US studies. Excess risks ranged from 0.06 to 13 cases/106 users/wk; the most strongly associated drugs were procainamide, anti‐thyroid drugs and sulphasalazine. An association with drugs that had previously been suspected was also seen in Thailand. The overall aetiologic fractions of agranulocytosis due to drug use were 62% in the IAAAS, 72% in the US and 70% in Thailand. Eleven drugs were significantly associated with an increased risk of aplastic anaemia, with excess risks ranging from 1.4 to 60 cases/106 users in a 5‐month period. The most strongly associated drugs were penicillamine, gold and carbamazepine. Aetiologic fractions were 27% in the IAAAS, 17% in the US and 2% in Thailand, which paralleled the prevalence of use of associated drugs in the 3 populations. The present results confirm that agranulocytosis is largely a drug‐induced disease, with similar proportions accounted for in 3 disparate geographic regions. By contrast, although many of the expected associations were observed for aplastic anaemia, most of the aetiology is not explained by drugs. For all associated drugs, the excess risks are sufficiently low that blood dyscrasias should not figure prominently in the balancing of risks and benefits.

Predictors of good function: The framingham study

This paper asks the question: among 1474 Framingham Study participants aged 35-68 years who were healthy at their fourth examination (1954-1958), what are the physiologic, behavioral, and demographic characteristics that distinguish those who survive and report good function from those who do not after 21 years of biennial observations? Although a larger proportion of women than men survived, their functional status was not as good. Multiple logistic regression analysis revealed that age, alcohol intake, cigarette smoking, ventricular rate, and education were all significantly related to functional status for men, with all but the last of these factors inversely related to good function. For women, the only significant predictor other than age was education, which, as with men, was directly associated with good function. The effect of education is probably mediated by numerous factors such as availability and use of health care services, quality of health care, occupation, and lifestyle.

The Ile585Val TRPV1 variant is involved in risk of painful knee osteoarthritis

Objective To assess if a coding variant in the gene encoding transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is associated with genetic risk of painful knee osteoarthritis (OA). Methods The Ile585Val TRPV1 variant encoded by rs8065080 was genotyped in 3270 cases of symptomatic knee OA, 1098 cases of asymptomatic knee OA and 3852 controls from seven cohorts from the UK, the USA and Australia. The genetic association between the low-pain genotype Ile–Ile and risk of symptomatic and asymptomatic knee OA was assessed. Results The TRPV1 585 Ile–Ile genotype, reported to be associated with lower thermal pain sensitivity, was associated with a lower risk of symptomatic knee OA in a comparison of symptomatic cases with healthy controls, with an odds ratio (OR) of 0.75 (95% CI 0.64 to 0.88; p=0.00039 by meta-analysis) after adjustment for age, sex and body mass index. No difference was seen between asymptomatic OA cases and controls (OR=1.02, 95% CI 0.82 to 1.27 p=0.86) but the Ile–Ile genotype was associated with lower risk of symptomatic versus asymptomatic knee OA adjusting for covariates and radiographic severity (OR=0.73, 95% CI 0.57 to 0.94 p=0.0136). TRPV1 expression in articular cartilage was increased by inflammatory cytokines (tumour necrosis factor α and interleukin 1). However, there were no differences in TRPV1 expression in healthy and arthritic synovial tissue. Conclusions A genotype involved in lower peripheral pain sensitivity is significantly associated with a decreased risk of painful knee OA. This indicates a role for the pro-nociceptive gene TRPV1 in genetic susceptibility to symptomatic knee OA, which may also be influenced by a role for this molecule in cartilage function.

Blood pressure in childhood. The National Health Examination Survey.

SUMMARY Data were analyzed from the U.S. Health Examination Surrey (Cycle II) to determine relationships between blood pressure and other characteristics. This survey examined a national probability sample of children aged 6-11 years. Signifkant relationships were found for blood pressure and the following variables: chronological and skeletal age, skinfold thickness (adiposity) and other anthropometric measurements, pulse rate, and systolic murmurs. These relationships may be interpreted as indicating important relationships between blood pressure and growth, adiposity, and hemodynamic manifestations of cardiac output. Data from this representative population portray blood pressure relationships in childhood.

Progress in the battle against hypertension. Changes in blood pressure levels in the United States from 1960 to 1980.

Intensive efforts by practicing physicians and public health workers to identify and treat persons with hypertension have been underway for many years. In this report, changes in blood pressure levels in the United States are assessed based on nationally representative health (and nutrition) examination surveys conducted by the National Center for Health Statistics in 1960 to 1962, 1971 to 1974, and 1976 to 1980. Analysis of age-adjusted data for adults aged 18 to 74 years (including those on antihypertensive medication) indicates that between the first and third surveys for whites and blacks, respectively, mean systolic blood pressure declined 5 and 10 mm Hg; the proportion of persons with systolic blood pressure of 140 mm Hg or higher fell 18 and 31%; the proportion with undiagnosed hypertension decreased 17 and 59%; and the proportion taking antihypertensive medications rose 71 and 31%. These differences between the first and third surveys were all statistically significant (p less than 0.05 or better). Changes in diastolic blood pressure levels were generally not significant among race-sex groups. The proportion of persons with definite hypertension (i.e., systolic blood pressure greater than or equal to 160 mm Hg, and/or diastolic blood pressure greater than or equal to 95 mm Hg, and/or taking antihypertensive medication) declined among blacks but rose slightly among whites. Study results are consistent with the recent decline in cardiovascular disease mortality.

Blood pressure in adolescence. The United States Health Examination survey.

SUMMARY A nationally representative sample of adolescents 12-17 years of age were examined in the U.S. Health Examination Survey and relationships between blood pressure and other variables were explored. During adolescence, blood pressure increases more rapidly in males than in females and only small racial differences are present. Weight has the strongest relationship to both systolic and diastolic pressure. Physiological maturation assessed by skeletal age and adiposity (skinfold thickness) are components of weight and each is also related to blood pressure. Although systolic murmurs are related to blood pressure at the time of examination, the murmurs are transitory and not predictive of future pressures. All factors were equally influential in each race-sex group. No significant relationships were found between geographic or demographic variables and blood pressure. These observations indicate the important relationships of physiological maturation and adiposity to adolescent blood pressure.

A role for PACE4 in osteoarthritis pain: evidence from human genetic association and null mutant phenotype

Objectives The aim of this study was to assess if genetic variation in the PACE4 (paired amino acid converting enzyme 4) gene Pcsk6 influences the risk for symptomatic knee osteoarthritis (OA). Methods Ten PCSK6 single nucleotide polymorphisms were tested for association in a discovery cohort of radiographic knee OA (n=156 asymptomatic and 600 symptomatic cases). Meta-analysis of the minor allele at rs900414 was performed in three additional independent cohorts (total n=674 asymptomatic and 2068 symptomatic). Pcsk6 knockout mice and wild-type C57BL/6 mice were compared in a battery of algesiometric assays, including hypersensitivity in response to intraplantar substance P, pain behaviours in response to intrathecal substance P and pain behaviour in the abdominal constriction test. Results In the discovery cohort of radiographic knee OA, an intronic single nucleotide polymorphism at rs900414 was significantly associated with symptomatic OA. Replication in three additional cohorts confirmed that the minor allele at rs900414 was consistently increased among asymptomatic compared to symptomatic radiographic knee OA cases in all four cohorts. A fixed-effects meta-analysis yielded an OR=1.35 (95% CI 1.17 to 1.56; p=4.3×10−5 and no significant between-study heterogeneity). Studies in mice revealed that Pcsk6 knockout mice were significantly protected against pain in a battery of algesiometric assays. Conclusions These results suggest that a variant in PCSK6 is strongly associated with protection against pain in knee OA, offering some insight as to why, in the presence of the same structural damage, some individuals develop chronic pain and others are protected. Studies in Pcsk6 null mutant mice further implicate PACE4 in pain.

Physical activity as a risk factor for osteoarthritis of the knee.

A case-control study was conducted to evaluate the association between knee osteoarthritis (OA) and physical activity (PA) among a community group aged 40 years and older. Case patients (85 males, 154 females) had radiologically confirmed knee OA with grade 2+ changes, according to Kellgren and Lawrence criteria. Control subjects (85 males, 154 females) had no radiologic evidence of knee OA. A statistically significant positive association between high PA level and knee OA was observed for women, with an age-adjusted odds ratio (OR) of 1.66 and 95% confidence interval (CI) of 1.01 to 2.72. In men no association was observed (OR = 0.95; 95% CI, 0.49 to 1.83). These associations persisted when controlling simultaneously for potential confounders including age, obesity, history of knee injury, and socioeconomic status, indicating that the OA-PA association is limited to women. One possible explanation is that risk factors for knee OA are influenced by hormones.