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Biomedical subjects

J David Spence

Publications and source records attributed to J David Spence.

At least 55 records · Page 3Linked to original sources
PubMed2004

Sex differences in carotid plaque and stenosis.

BACKGROUND AND PURPOSE: Women are relatively protected from cardiovascular events; they are 3 times as likely as men to survive to age 90 years. Although clinical trials show an excess of thrombotic events with estrogen/progestin hormone replacement therapy, much experimental and epidemiological evidence suggests that estrogen may have beneficial effects on endothelial function and atherosclerosis, raising the possibility of sex differences in arterial remodeling. We studied sex differences in carotid plaque and stenosis in relation to survival free of stroke, death, and myocardial infarction. METHODS: A total of 1686 patients from an atherosclerosis prevention clinic were followed annually for up to 5 years (mean, 2.5+/-1.3 years) with baseline and follow-up measurements; there were 45 strokes, 94 myocardial infarctions, and 41 deaths. RESULTS: Carotid stenosis and plaque increased with age. Women had greater stenosis compared with men (P=0.001), whereas men had greater plaque area than did women at all ages (P<0.0001). Stroke, myocardial infarction, and death combined were predicted significantly by plaque area (P=0.004) but not by stenosis (P=0.042). CONCLUSIONS: Women have more stenosis but less plaque than men, suggesting that differences in sex hormones may affect remodeling of atherosclerosis. Plaque area was a stronger predictor of outcomes than was stenosis.

Age Distribution↗
PubMed2004

Non-invasive assessment of atherosclerosis risk.

The reasons to measure atherosclerosis include 1) risk stratification and prediction; 2) evaluation of patient response to interventions; and 3) identification of novel genetic, cellular and molecular determinants of risk. Atherosclerosis can be quantified non-invasively using the increasingly reliable and precise modalities described in this issue, which include ultrasound and magnetic resonance imaging. While each modality assesses "atherosclerosis", the particular morphological entities captured may reflect different aspects of atherogenesis with different biological determinants. For instance, among carotid ultrasound determinations, intima-media thickness (IMT) may reflect medial hypertrophy from hypertension, while plaque volume and stenosis and calcium deposition may additionally reflect foam cell proliferation, scarring and/or thrombosis. Clarifying the biological and clinical correlates of images may guide the choice of modality for specific applications. In addition, these tools are presently used to assess structures at a single time point. However, using them to follow temporal changes may further enhance their value. In this regard, certain modalities, such as ultrasound assessment of carotid plaque area or volume, may be more sensitive than others, such as assessment of IMT, for detecting temporal changes in atherosclerosis. Combining modalities--and adding new biomarkers of disease--may be necessary to grasp the full complex vascular phenotypic picture--"phenomics"--of both individual subjects and groups of patients. In evaluating new determinants and novel therapies, it will be important to consider the biology and clinical correlates of a specific measured atherosclerosis phenotype in order to select the most appropriate modality.

Arteriosclerosis↗
PubMed2004

3D ultrasound imaging of the carotid arteries.

Although ultrasonography is an important cost-effective imaging modality, technical improvements are needed before its full potential is realized for accurate and reproducible monitoring of carotid disease and plaque burden. 2D viewing of 3D anatomy, using conventional ultrasonography limits our ability to quantify and visualize carotid disease and is partly responsible for the reported variability in diagnosis and monitoring of disease progression. Efforts of investigators have focused on overcoming these deficiencies by developing 3D ultrasound imaging techniques that are capable of acquiring B-mode, color Doppler and power Doppler images of the carotid arteries using existing conventional ultrasound systems, reconstructing the information into 3D images, and then allowing interactive viewing of the 3D images on inexpensive desktop computers. In addition, the availability of 3D ultrasound images of the carotid arteries has allowed the development of techniques to quantify plaque volume and surface morphology as well as allowing registration with other 3D imaging modalities. This paper describes 3D ultrasound imaging techniques used to image the carotid arteries and summarizes some of the developments aimed at quantifying plaque volume and morphology.

Carotid Arteries↗
PubMed2004

Effects of perindopril on elastic and structural properties of large arteries in essential hypertension.

BACKGROUND: Perindopril, an angiotensin-converting enzyme (ACE) inhibitor, is a well-recognized antihypertensive drug. Its ability to protect against cardiovascular events in hypertension has also been demonstrated. It decreases the stiffness of the larger arteries; questions remain as to the mechanisms involved and whether it is blood pressure (BP) control-dependent. OBJECTIVES: To correlate the BP response to ACE inhibition therapy with changes in arterial stiffness as evaluated by pulse wave velocity (PWV), and to correlate these changes in arterial stiffness with alterations in indicators of vascular collagen metabolism serum levels of metalloproteinase (MMP)-1 and tissue inhibitor of MMP-1 (TIMP-1). METHODS: A total of 162 patients aged 18 to 70 years with stage 1 and 2 essential hypertension (diastolic BP 95 mmHg to 114 mmHg) were enrolled to receive six months (M6) of therapy with the ACE inhibitor, perindopril. Patients were either treatment-naïve or had not received any antihypertensive treatment for at least six months before the study. RESULTS: Mean BP was significantly reduced after two months (M2) of therapy (P=0.00001) and remained stable thereafter. In addition to the significant mean changes in PWV observed at M2 (P=0.00001), further reductions in PWV were noted at M6 (P=0.007). The change in PWV between baseline (M0) and M2 was significantly correlated to all BP parameters at M0 (correlation coefficient at M2 was 0.189 or greater). However, no correlation was seen regarding BP parameters at M2 and further M2 to M6 changes in PWV, suggesting a decrease of arterial stiffness independent of BP reduction. The expression of TIMP-1 and MMP-1 was highly variable and demonstrated no correlation with BP or PWV. CONCLUSIONS: Reductions in BP and PWV appear to be correlated during the first two months of perindopril therapy. After six months, PWV continues to decrease independently of any further reduction in BP, suggesting the occurrence of a pressure-independent pharmacological remodelling of the arterial wall. A long-term, double-blind, randomized trial could be required to confirm that the observed increase in vascular distensibility induced by perindopril is related to a mechanism of action other than a reduction in BP.

Adolescent↗
PubMed2004

Dimercaptosuccinic acid for the treatment of hyperhomocysteinemia in hemodialysis patients: a placebo-controlled, double-blind, randomized trial.

BACKGROUND: Elevated total homocysteine (tHcy) levels may represent a potentially modifiable risk factor for cardiovascular disease in hemodialysis patients. Current therapies, including multivitamins, have been ineffective at normalizing homocysteine levels in this population; hence, new therapies are needed. There is increasing interest in the use of thiol pharmaceutical agents to displace homocysteine from albumin and improve its dialyzability. We designed a randomized, double-blind, placebo-controlled trial to determine the effect of prolonged administration of oral dimercaptosuccinic acid (DMSA) on plasma tHcy levels in vitamin-replete hemodialysis patients. METHODS: Forty-four long-term stable dialysis patients were treated for a minimum of 4 weeks with a standard multivitamin, ensuring a vitamin-replete state, then matched on the basis of tHcy levels and randomly assigned as pairs to the administration of DMSA, 2.5 mg/kg/d, or identical placebo for 8 weeks. Multivitamins were continued for the duration of the trial. RESULTS: Thirty-eight subjects (including 16 pairs) completed the trial. All important determinants of homocysteine level were balanced, and the only significant baseline difference was weight (P = 0.02). At 8 weeks, by paired analysis, there was no statistically significant difference in tHcy levels between the placebo and DMSA groups, at 21.2 micromol/L (2.87 mg/L) and 22.6 micromol/L (3.06 mg/L), respectively (mean difference, -1.4; 95% confidence interval, -5.3 to 2.5; P = 0.45). The same was true for unpaired and multivariable analyses. CONCLUSION: This randomized placebo-controlled trial found that prolonged oral administration of the thiol DMSA had no impact on tHcy levels in hemodialysis patients. Additional strategies to test the homocysteine hypothesis in this population require investigation.

Administration, Oral↗
PubMed2003

Lipoprotein lipase (LPL) gene variation and progression of carotid artery plaque.

BACKGROUND AND PURPOSE: Coding single nucleotide polymorphisms (cSNPs) in the lipoprotein lipase (LPL) gene have been associated with lipoprotein phenotypes and vascular disease risk. We studied the association between LPL cSNPs and a novel noninvasive measure of disease, namely, cross-sectional carotid plaque area (CPA) on B-mode ultrasound. METHODS: Four hundred fifty-two patients from an atherosclerosis prevention clinic had determinations of baseline and total CPA. Traditional atherosclerosis risk factors were recorded, and the LPL D9N, N291S, and S447X cSNPs were genotyped. Multiple regression analysis was used to identify determinants of CPA. RESULTS: Minor allele frequencies for LPL D9N, N291S, and S447X were 2.8%, 0.9%, and 4.4%, respectively. There were no significant between-genotype differences in treated fasting lipids. The LPL D9N genotype was a significant predictor of both baseline CPA (P=0.008) and plaque progression from baseline to 1 year later (P=0.001). Heterozygotes for the N9 allele had higher mean baseline CPA and plaque progression than did LPL D9/D9 homozygotes. CONCLUSIONS: LPL D9N genotype may be a determinant of atherosclerosis as estimated by static baseline CPA and by progression of CPA.

Adult↗
PubMed2003

Motor vehicle accidents: the most common cause of traumatic vertebrobasilar ischemia.

BACKGROUND: Recent media exposure of strokes from chiropractic manipulation have focused attention on traumatic vertebrobasilar ischemia. However, chiropractic manipulation, while the easiest cause to recognize, is probably not the most common cause of this condition. METHODS: We reviewed all consecutive cases of traumatic vertebrobasilar ischemia referred to a single neurovascular practice over 20 years, from the office files and hospital records. RESULTS: There were 80 patients whose vertebrobasilar ischemia was attributed to neck trauma. Five were diagnosed as due to chiropractic manipulation, but the commonest attributed cause was motor vehicle accidents (MVAs), which accounted for 70 cases; one was a sports injury, and five were industrial accidents. In some cases neck pain from an MVA led to chiropractic manipulation, so the cause may have been compounded. In most vehicular cases the diagnosis had been missed, even denied, by the neurologists and neurosurgeons initially involved. The longest delay between the injury and the onset of delayed symptoms was five years. CONCLUSIONS: Traumatic vertebrobasilar ischemia is most often due to MVAs; the diagnosis is often missed, in part because of the delay between injury and onset of symptoms and, in part, we hypothesize, because of reluctance of doctors to be involved in medicolegal cases.

Accidents, Traffic↗
PubMed2003

The effect of flax seed cultivars with differing content of alpha-linolenic acid and lignans on responses to mental stress.

BACKGROUND: Phytoestrogens offer a possible alternative to hormone replacement therapy. Flax seed contains large quantities of a phytoestrogen precursor, secoisolariciresinol diglucoside (SDG), as well as large quantities of alpha-linolenic acid; these factors may be protective against vascular disease. We have previously shown that the rise in blood pressure during mental stress is a strong predictor of atherosclerosis progression. METHODS: 35 postmenopausal women with vascular disease, 62 +/- 8 years of age, were treated in a random-sequence double-blind Latin square crossover study comparing three strains of flax seed: Flanders (low in lignan and high in alpha-linolenic acid), Linola 989 (high in lignan and low in alpha-linolenic acid) and AC Linora (intermediate in both lignan and alpha-linolenic acid). RESULTS: Compared to the pre-treatment baseline diet, all three strains of flax significantly reduced blood pressure during mental stress induced by a frustrating cognitive task (Stroop color-word interference task) (p = 0.004). Linola 989, the strain highest in lignan and lowest in alpha-linolenic acid, was associated with the least increase in peripheral resistance during stress, the greatest reduction in plasma cortisol during stress and the smallest increase in plasma fibrinogen during mental stress. CONCLUSION: Flax phytoestrogens ameliorate certain responses to stress and thus may afford protection against atherosclerosis; this hypothesis should be tested in clinical trials.

Aged↗
PubMed2003

Measurement of carotid plaque and effect of vitamin therapy for total homocysteine.

BACKGROUND: Many new therapies are being developed that are anti-atherosclerotic, but which do not change clinical parameters such as blood pressure or cholesterol. In order to measure the effects of these therapies it will be necessary to measure atherosclerosis. Elevated levels of plasma total homocysteine (tHcy) are associated with increased risk of stroke and myocardial infarction. Measurement of the effect of vitamin therapy on atherosclerosis has therefore been used as an example of this approach. METHODS: 2-Dimensional measurement of carotid plaque cross-sectional area has been used to measure effects of vitamin therapy in patients whose plaque is progressing despite intensive treatment of traditional risk factors. In clinic patients, addition of vitamin therapy halted progression of atherosclerosis, in samples of 50 patients over 2.5 years. However, in patients randomized to high-dose vs. low-dose vitamins in the Vitamin Intervention for Stroke Prevention trial, no difference in plaque progression was seen between high-dose and low-dose vitamin therapy. New methods have been developed for the measurement of 3-dimensional plaque volume, and for the measurement of plaque surface roughness. RESULTS: The accuracy and reliability of the measurement of plaque volume is 95%. This will permit measurement of effects of new anti-atherosclerotic therapies with much smaller sample sizes, in a much shorter time, than previously available methods such as intima-media thickness. CONCLUSION: Measurement of atherosclerotic plaque volume and roughness will greatly enhance the study of new anti-atherosclerotic therapies.

Aged↗
PubMed2003

Nutritional and metabolic aspects of stroke prevention.

Epidemiologic evidence, animal studies, angiographic and ultrasound studies in humans, and a limited number of clinical trials suggest that vitamins C and E may be protective and that folate, B6, and B12, by lowering homocysteine levels, may reduce stroke. However, these hypotheses require testing before widespread use of supplementary vitamins can be generally recommended (62). Clinical trials under way will test those hypotheses. In the meantime, it should be understood that the role of diet is much more important than is widely recognized. A diet low in saturated fat and cholesterol, low in sodium, high in potassium and calcium, and containing a lot of fruits and vegetables reduces blood pressure as much as an antihypertensive drug and in coronary patients is twice as effective as statin drugs in reducing death and myocardial infarction. Such a diet can therefore be confidently recommended as a source not only of natural proportions of vitamins and antioxidants but also for benefits that we are only beginning to define.

Animals↗
PubMed2003

Fasting lipids: the carrot in the snowman.

The current paradigm for the management of lipids is focused almost entirely on fasting lipid levels. However, most of the day is spent not in a fasting state, but in a postprandial state. Meals high in animal fat impair endothelial function for 4 h, an effect that can be minimized by pretreatment with antioxidant vitamins. Dietary cholesterol (one egg yolk), though it increases fasting low density lipoproteins by only about 10%, increases oxidized low-density lipoproteins by 34%. Two studies in coronary patients, the Lyon Diet Heart Study and the IndoMediterranean Diet study, have shown that, despite no difference in fasting lipid levels, a Mediterranean diet reduced myocardial infarction and death by 60% in four years and by 50% in two years compared with diets amounting to the American Heart Association diet that is usually prescribed to coronary patients. It is time to stop focusing only on fasting lipid levels and to begin paying more attention to outcomes.

Coronary Disease↗