Richard J. Havlik

Elevated Aortic Pulse Wave Velocity, a Marker of Arterial Stiffness, Predicts Cardiovascular Events in Well-Functioning Older Adults

Background—Aging results in vascular stiffening and an increase in the velocity of the pressure wave as it travels down the aorta. Increased aortic pulse wave velocity (aPWV) has been associated with mortality in clinical but not general populations. The objective of this investigation was to determine whether aPWV is associated with total and cardiovascular (CV) mortality and CV events in a community-dwelling sample of older adults. Methods and Results—aPWV was measured at baseline in 2488 participants from the Health, Aging and Body Composition (Health ABC) study. Vital status, cause of death and coronary heart disease (CHD), stroke, and congestive heart failure were determined from medical records. Over 4.6 years, 265 deaths occurred, 111 as a result of cardiovascular causes. There were 341 CHD events, 94 stroke events, and 181 cases of congestive heart failure. Results are presented by quartiles because of a threshold effect between the first and second aPWV quartiles. Higher aPWV was associated with both total mortality (relative risk, 1.5, 1.6, and 1.7 for aPWV quartiles 2, 3, and 4 versus 1; P=0.019) and cardiovascular mortality (relative risk, 2.1, 3.0, and 2.3 for quartiles 2, 3, and 4 versus 1; P=0.004). aPWV quartile was also significantly associated with CHD (P=0.007) and stroke (P=0.001). These associations remained after adjustment for age, gender, race, systolic blood pressure, known CV disease, and other variables related to events. Conclusions—Among generally healthy, community-dwelling older adults, aPWV, a marker of arterial stiffness, is associated with higher CV mortality, CHD, and stroke.

Trends and Disparities in Coronary Heart Disease, Stroke, and Other Cardiovascular Diseases in the United States Findings of the National Conference on Cardiovascular Disease Prevention

A workshop was held September 27 through 29, 1999, to address issues relating to national trends in mortality and morbidity from cardiovascular diseases; the apparent slowing of declines in mortality from cardiovascular diseases; levels and trends in risk factors for cardiovascular diseases; disparities in cardiovascular diseases by race/ethnicity, socioeconomic status, and geography; trends in cardiovascular disease preventive and treatment services; and strategies for efforts to reduce cardiovascular diseases overall and to reduce disparities among subpopulations. The conference concluded that coronary heart disease mortality is still declining in the United States as a whole, although perhaps at a slower rate than in the 1980s; that stroke mortality rates have declined little, if at all, since 1990; and that there are striking differences in cardiovascular death rates by race/ethnicity, socioeconomic status, and geography. Trends in risk factors are consistent with a slowing of the decline in mortality; there has been little recent progress in risk factors such as smoking, physical inactivity, and hypertension control. There are increasing levels of obesity and type 2 diabetes, with major differences among subpopulations. There is considerable activity in population-wide prevention, primary prevention for higher risk people, and secondary prevention, but wide disparities exist among groups on the basis of socioeconomic status and geography, pointing to major gaps in efforts to use available, proven approaches to control cardiovascular diseases. Recommendations for strategies to attain the year 2010 health objectives were made.

Midlife blood pressure and dementia: the Honolulu–Asia aging study☆ ☆

We studied the association of mid-life blood pressure to late age dementia, specifically Alzheimers disease and vascular dementia. Data are from the cohort of 3703 Japanese-American men who were followed in the Honolulu Heart Program (HHP;1965-1971), and subsequently re-examined in 1991 for dementia. We assessed the risk (odds ratio (95% CI)) for dementia associated with categories of systolic (SBP) and diastolic blood pressure (DBP), stratified by never/ever treatment with anti-hypertensive medications, and adjusting for age, education, apolipoprotein epsilon allele, smoking and alcohol intake. Among those never treated (57% sample), the risk for dementia was OR 95% CI 3.8 (1.6-8.7) for DBP of 90-94 mm Hg, and 4. 3 (1.7-10.8) for DBP of 95 mmHg and over compared to those with DBP of 80 to 89 mm Hg. Compared to those with SBP of 110 to 139 mm Hg, the risk for dementia was 4.8 (2.0-11.0) in those with SBP 160 mm Hg and higher. Blood pressure was not associated with the risk for dementia in treated men. These results were consistent for Alzheimers disease and vascular dementia. This study suggests elevated levels of blood pressure in middle age can increase the risk for late age dementia in men never treated with anti-hypertensive medication.

Serum IL-6 level and the development of disability in older persons

BACKGROUND: The serum concentration of interleukin 6 (IL‐6), a cytokine that plays a central role in inflammation, increases with age. Because inflammation is a component of many age‐associated chronic diseases, which often cause disability, high circulating levels of IL‐6 may contribute to functional decline in old age. We tested the hypothesis that high levels of IL‐6 predict future disability in older persons who are not disabled.

Documented head injury in early adulthood and risk of Alzheimer’s disease and other dementias

Background: The association between antecedent head injury and AD is inconsistent. Objective: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE ε4 as risk factors for dementia. Methods: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models. Results: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE ε4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more ε4 alleles. Conclusions: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.

Association of vitamin E and C supplement use with cognitive function and dementia in elderly men.

Objective: To determine whether use of vitamin E and C supplements protects against subsequent development of dementia and poor cognitive functioning. Methods: The Honolulu–Asia Aging Study is a longitudinal study of Japanese-American men living in Hawaii. Data for this study were obtained from a subsample of the cohort interviewed in 1982, and from the entire cohort from a mailed questionnaire in 1988 and the dementia prevalence survey in 1991 to 1993. The subjects included 3,385 men, age 71 to 93 years, whose use of vitamin E and C supplements had been ascertained previously. Cognitive performance was assessed with the Cognitive Abilities Screening Instrument, and subjects were stratified into four groups: low, low normal, mid normal, and high normal. For the dementia analyses, subjects were divided into five mutually exclusive groups: AD (n = 47), vascular dementia (n = 35), mixed/other types of dementia (n = 50), low cognitive test scorers without diagnosed dementia (n = 254), and cognitively intact (n = 2,999; reference). Results: In a multivariate model controlling for other factors, a significant protective effect was found for vascular dementia in men who had reported taking both vitamin E and C supplements in 1988 (odds ratio [OR], 0.12; 95% CI, 0.02 to 0.88). They were also protected against mixed/other dementia (OR, 0.31; 95% CI, 0.11 to 0.89). No protective effect was found for Alzheimer’s dementia (OR, 1.81; 95% CI, 0.91 to 3.62). Among those without dementia, use of either vitamin E or C supplements alone in 1988 was associated significantly with better cognitive test performance at the 1991 to 1993 examination (OR, 1.25; 95% CI, 1.04 to 1.50), and use of both vitamin E and C together had borderline significance (OR, 1.18; 95% CI, 0.995 to 1.39). Conclusions: These results suggest that vitamin E and C supplements may protect against vascular dementia and may improve cognitive function in late life.

Midlife blood pressure and neuritic plaques, neurofibrillary tangles, and brain weight at death: the HAAS <

Midlife hypertension is associated with later development of cognitive impairment, vascular dementia (VsD), and possibly Alzheimers disease (AD). Neuropathic cerebrovascular lesions and brain atrophy have been associated with elevated blood pressure (BP), however, to our knowledge there have been no prospective investigations of an association of blood pressure levels measured in midlife with the microscopic lesions of AD. We investigated the relationship of BP level in midlife to development of neurofibrillary tangles (NFT), neuritic plaques (NP), and low brain weight at autopsy among Japanese-American men who were members of the Honolulu Heart Program/Honolulu-Asia aging Study (HHP/HAAS) cohort. The HHP/HAAS is a population-based, longitudinal study of cognitive function and dementia with 36 years of follow-up. Neocortical and hippocampal NFT and NP were counted per mm(2), and fixed brain weight was measured for 243 decedents. Elevated systolic BP, (> or =160 mm Hg) in midlife was associated with low brain weight and greater numbers of NP in both neocortex and hippocampus. Diastolic BP elevation, (> or =95 mm Hg) was associated with greater numbers of NFT in hippocampus. Results indicate that in addition to the accepted association of high BP with neuropathic cerebrovascular lesions, there is a direct relationship with brain atrophy, NP and NFT.

Aortic Stiffness Is Associated With Visceral Adiposity in Older Adults Enrolled in the Study of Health, Aging, and Body Composition

The central arteries stiffen with age, causing hemodynamic alterations that have been associated with cardiovascular events. Changes in body fat with age may be related to aortic stiffening. The association between vascular stiffness and body fat was evaluated in 2488 older adults (mean age, 74 years; 52% female; 40% black) enrolled in the Study of Health, Aging, and Body Composition (Health ABC), a prospective study of changes in weight and body composition. Clinical sites were located in Pittsburgh, Pa, and Memphis, Tenn. Aortic pulse wave velocity was used as an indirect measure of aortic stiffness. A faster pulse wave velocity indicates a stiffer aorta. Body fat measures were evaluated with dual energy x-ray absorptiometry and computed tomography. Independent of age and blood pressure, pulse wave velocity was positively associated with weight, abdominal circumference, abdominal subcutaneous fat, abdominal visceral fat, thigh fat area, and total fat (P <0.001 for all). The strongest association was with abdominal visceral fat. Elevated pulse wave velocity was also positively associated with history of diabetes and higher levels of glucose, insulin, and hemoglobin A1c (P <0.001 for all). In multivariate analysis, independent positive associations with pulse wave velocity were found for age, systolic blood pressure, heart rate, abdominal visceral fat, smoking, hemoglobin A1c, and history of hypertension. The association between pulse wave velocity and abdominal visceral fat was consistent across tertiles of body weight. Among older adults, higher levels of visceral fat are associated with greater aortic stiffness as measured by pulse wave velocity.

Calcium-channel blockade and incidence of cancer in aged populations

BACKGROUND Calcium-channel blockers can alter apoptosis, a mechanism for destruction of cancer cells. We examined whether the long-term use of calcium-channel blockers is associated with an increased risk of cancer. METHODS Between 1988 and 1992 we carried out a prospective cohort study of 5052 people aged 71 years or more and who lived in three regions of Massachusetts, Iowa, and Connecticut USA. Those taking calcium-channel blockers (n = 451) were compared with all other participants (n = 4601). The incidence of cancer was assessed by survey of hospital discharge diagnoses and causes of death. These outcomes were validated by the cancer registry in the one region where it was available. Demographic variables, disability, cigarette smoking, alcohol consumption, blood pressure, body-mass index, use of other drugs, hospital admissions for other causes, and comorbidity were all assessed as possible confounding factors. FINDINGS The hazard ratio for cancer associated with calcium-channel blockers (1549 person-years, 47 events) compared with those not taking calcium-channel blockers (17225 person-years, 373 events) was 1.72 (95% CI 1.27-2.34, p = 0.0005), after adjustment for confounding factors. A significant dose-response gradient was found. Hazard ratios associated with verapamil, diltiazem, and nifedipine did not differ significantly from each other. The results remained unchanged in community-specific analyses. The association between calcium-channel blockers and cancer was found with most of the common cancers. INTERPRETATION Calcium-channel blockers were associated with a general increased risk of cancer in the study populations, which suggested a common mechanism. These observational findings should be confirmed by other studies.

Long-Term Survival and Use of Antihypertensive Medications in Older Persons

OBJECTIVE: To determine whether older persons with hypertension who use specific calcium antagonists and ACE inhibitors have a different risk of mortality than those using β‐blockers.