Mathematical estimation of the potential effect of vascular remodelling/dilatation on B-mode ultrasound intima-medial thickness.

BACKGROUND: Arterial diameter changes are known to impact wall thickness, but the clinical relevance of the changes is unclear. AIM: To use known mathematical relationships to estimate anticipated changes in arterial wall thicknesses occurring with enlargement of atherosclerotic regions. DESIGN: Mathematical relationships between a cylinder's diameter and its wall thickness were used to calculate the theoretical effect of diameter enlargement on the thickness of an atherosclerotic wall. METHODS: Equating the wall areas of two cylinders, one of smaller diameter than the other, allowed estimation of the degree of thickening that would be needed to maintain intima-medial thickness (IMT) after arterial remodelling. The difference in cylinder diameters was based on arterial diameter enlargement reported with atherosclerosis progression. Thus, the calculated wall changes estimate arterial changes which could go undetected if only IMT is measured by ultrasound. RESULTS: The expected IMT change for diameter enlargement is not a linear function of the diameter change, but varies depending upon initial size (diameter and IMT). Thus a 0.6 mm arterial diameter enlargement would be expected to cause a 0.039-0.235 mm change in IMT, depending on artery size. The estimated IMT change is similar to that associated with major atherosclerotic risk factors. DISCUSSION: The level of vascular remodelling reported with atherosclerosis could have a measurable impact on IMT, suggesting that indicators incorporating both diameter and IMT may be better disease indicators than IMT alone. Arterial diameters, as well as IMT, should be obtained in ultrasound studies of atherosclerosis.

Elemental analysis of soft plaque and calcified plaque deposits from human coronary arteries and aorta.

Twenty-five samples of soft plaque and calcified plaque deposits from human hearts or aorta were analyzed using inductively coupled plasma-mass spectrometry (ICP-MS). The determined elements were Ca, P, Na, K, Mg, Zn, Cu, Ba, Pb, Fe, Al, Si, and S. Results showed that the concentration of all elements in the soft plaque was at the micromolar level. In the calcified deposits, the concentrations of Ca and P were at least an order of magnitude higher than the soft plaque, but the other elements were at the same order of magnitude. In the calcified plaque the molar ratios of Ca/P suggested that a significant portion existed as hydroxyapatite Ca10(PO4)6(OH)3. However, their absolute concentrations indicated that this compound was not a major component of the plaque although it may play a major role in determining the crystal structure of the deposit. In some samples the Ca/P ratio was too high to conform to hydroxyapatite. In others it was too low. This indicated that both the calcium and phosphorus existed in other chemical forms which varied from sample to sample. In the soft tissue the P level was high indicating it existed primarily in chemical forms other than hydroxyapatite. The presence of homocysteine is often associated with heart disease. However, the low levels of sulfur indicate that although it may be present, it is not a major component of the plaque, but may nevertheless play an important role in its formation.

Atherosclerosis in youth.

BACKGROUND: Coronary heart disease (CHD) and the related diseases due to atherosclerosis continue to be major public health problems in the industrialized countries and are likely to become serious problems in the developing countries. Treatment of end stage disease has improved, and risk factor modification has succeeded in reducing risk among adults. However, the age at which to begin risk factor control for long-range primary prevention is controversial. METHODS: A multicenter cooperative study, Pathobiological Determinants of Atheroscle-rosis in Youth (PDAY), was organized in 1985 to examine the relationship of the risk factors for adult CHD to preclinical atherosclerotic lesions in youth. Fourteen participating centers collected arteries, blood, other tissue, and data from 3,000 persons 15-34 years of age who died from external causes and were autopsied in forensic laboratories. Central laboratories evaluated atherosclerosis in the aorta and coronary arteries, measured lipoproteins and thio-cyanate (for smoking) in serum, glycohemo-globin in red blood cells (for blood glucose), thickness of small renal arteries (for hypertension), and body mass index (for obesity). The data were analyzed to determine the progression of atherosclerosis with age in both sexes and the association of the risk factors with atherosclerotic lesions. RESULTS: Raised lesions of the coronary arteries, the advanced lesions of atherosclerosis that lead directly to CHD, are associated positively with non-HDL cholesterol concentration, hypertension, obesity (in men), and blood glucose concentration; and inversely, with HDL cholesterol concentration. Smoking affects predominantly the abdominal aorta. CONCLUSIONS: These results suggest that long-range prevention of CHD should begin in adolescence or at least in young adulthood with control of the major established risk factors for adult CHD.

A method to fix lipids for staining fat embolism in paraffin sections.

AIMS: To develop a method to preserve lipids in formalin-fixed tissues for staining in paraffin sections, and to illustrate its use in lung and brain of a fat embolism case, and in examples of fatty liver and atheroma. METHODS AND RESULTS: A saturated solution of linoleic acid in 70% ethylene glycol was prepared and tissues were exposed to this for 3 days at 56 degrees C. These tissues were treated with 2% chromic acid at 4 degrees C for 24 h followed by 24 h in 5% sodium bicarbonate, with appropriate rinsing between solutions. Paraffin sections of these tissues were stained with a lipid-soluble dye such as Oil Red O. Examples of fat embolism, fatty liver, and atheroma were shown photographically as illustrations of expected results. CONCLUSIONS: The demonstration of fat embolism with good quality tissue detail is made practical by the method, which is convenient and inexpensive. The method appears to be generally applicable to tissue lipids of various sorts, as exemplified by adipose tissue, fatty liver, and atheroma.

Effects of nonlipid risk factors on atherosclerosis in youth with a favorable lipoprotein profile.

BACKGROUND: The strong association between coronary heart disease and dyslipoproteinemia has often overshadowed the effects of the nonlipid risk factors-smoking, hypertension, obesity, and diabetes and impaired glucose tolerance-and even led to questioning the importance of these risk factors in the presence of a favorable lipoprotein profile. METHODS AND RESULTS: A cooperative multicenter study, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY), examined the relation of the nonlipid risk factors to atherosclerosis in 629 men and 227 women 15 to 34 years of age who died of external causes and who had a favorable lipoprotein profile (non-HDL cholesterol <4.14 mmol/L [<160 mg/dL] and HDL cholesterol >/=0.91 mmol/L [>/=35 mg/dL]). In the abdominal aorta, smokers had more extensive fatty streaks and raised lesions than nonsmokers, and hypertensive blacks had more raised lesions than normotensive blacks. In the right coronary artery, hypertensive blacks had more raised lesions than normotensive blacks, obese men (body mass index >/=30 kg/m(2)) had more extensive fatty streaks and raised lesions than nonobese men, and individuals with impaired glucose intolerance had more extensive fatty streaks. Obese men had more severe lesions (American Heart Association grade 2 through 5) of the left anterior descending coronary artery. CONCLUSIONS: These substantial effects of the nonlipid risk factors on the extent and severity of coronary and aortic atherosclerosis, even in the presence of a favorable lipoprotein profile, support the need to control all cardiovascular risk factors.

Medial thickenings of coronary artery and the aging risk factor for atherosclerosis.

The objective here is to inquire what kind of coronary artery is it that tends to acquire atheroma: When an atheroma is found somewhere in the specimen (YesA specimen), what do we see in the specimen far away from the atheroma? Previous studies found thicker intima in YesA specimens than in NoA specimens, but with equal numbers of smooth muscle cells (SMC's). Thickness per SMC strongly predicted atheroma, so much so that the risk factor age was fully explained statistically. This study now finds that the medial layer is also thicker in YesA specimens, and with medial SMC numbers equal to those in NoA specimens. Hence, the aging risk factor appears to induce excessive thickness per SMC as a generalized property throughout the whole specimen in the medial as well as intimal layers, with excessive production of collagenous matrix acting as an initial, rate limiting step in plaque formation. In the intima, atheroma tends to occur when average thickness per SMC exceeds the threshold value of 8.6 microm/SMC. The extreme high value found in the most severely affected medial sample was 4.2 microm/SMC, and this failure to approach the threshold could explain the medial resistance to fatty degenerations.

Origin of atherosclerosis in childhood and adolescence.

Atherosclerosis begins in childhood as deposits of cholesterol and its esters, referred to as fatty streaks, in the intima of large muscular arteries. In some persons and at certain arterial sites, more lipid accumulates and is covered by a fibromuscular cap to form a fibrous plaque. Further changes in fibrous plaques render them vulnerable to rupture, an event that precipitates occlusive thrombosis and clinically manifest disease (sudden cardiac death, myocardial infarction, stroke, or peripheral arterial disease). In adults, elevated non-HDL-cholesterol concentrations, low HDL-cholesterol concentrations, hypertension, smoking, diabetes, and obesity are associated with advanced atherosclerotic lesions and increased risk of clinically manifest atherosclerotic disease. Control of these risk factors is the major strategy for preventing atherosclerotic disease. To determine whether these risk factors also are associated with early atherosclerosis in young persons, we examined arteries and tissue from approximately 3000 autopsied persons aged 15-34 y who died of accidental injury, homicide, or suicide. The extent of both fatty streaks and raised lesions (fibrous plaques and other advanced lesions) in the right coronary artery and in the abdominal aorta was associated positively with non-HDL-cholesterol concentration, hypertension, impaired glucose tolerance, and obesity and associated negatively with HDL-cholesterol concentration. Atherosclerosis of the abdominal aorta also was associated positively with smoking. These observations indicate that long-range prevention of atherosclerosis and its sequelae by control of the risk factors for adult coronary artery disease should begin in adolescence and young adulthood.

Hypertensive renovasculopathies and the rise of blood pressure with age in Japan and USA.

Arterial intimal fibroplasia in renal interlobular arteries but not arteriolar hyalinization was reported to be proportional to the rise of blood pressure with age in the data from all populations examined so far. New findings from Japan offer further insights into the disparities between the two types of renovasculopathy, both of which are called by the same name, 'arteriolosclerosis'. PAS stained paraffin sections were prepared from specimens obtained at autopsy in Tokyo and New Orleans, emphasizing basal subjects, i.e. those with no cause of death known to be related to hypertension. Severities of fibroplastic vasculopathy, in units of intimal thickness as % of outer diameter, and hyaline vasculopathy, in units of affected arterioles per cm2 of tissue sectional area, were measured morphometrically. Blood pressure data were taken from published population surveys. Fibroplastic renovasculopathy was found to provide a proxy for mean blood pressure (MBP) when comparing groups of men and women of various age groups in the USA and Japan. Hyaline renovasculopathy did not reproduce these patterns. Some of these findings confirm similar results from prior studies, and this reproducibility increases confidence that a true biological difference may exist between these populations.

Recent declines of hypertensive renovasculopathies in New Orleans blacks.

Some evidence indicates that renovasculopathies measured in paraffin sections of renal cortex obtained at autopsy might offer a general guide to prevailing mean blood pressure (MBP) in the averages of demographic groups. In this study, data on forensic autopsies done in New Orleans from 1968 to 1998 were retrieved from computer archives. Observations are confined to basal cases (ie, those with causes of death having no known correlation with hypertension and therefore, who can be taken as approximately representative of the sampled populations, although overt hypertensives may be underrepresented in such a series). MBP derived from renovasculopathies were used to follow birth date cohorts born around the years 1928, 1938, 1948, 1958, 1968, and 1978. Vasculopathy-derived MBP of white men and women increased with age in a stable pattern with no shifting of positions among the cohorts. This pattern offered a baseline for comparison with the data on blacks. Against this baseline, blacks displayed the highest MBP in the earliest cohort with stair-step declines in later born cohorts, and an abrupt decrease between the 1958 and 1968 cohorts. Data from National Health And Nutrition Examination Surveys are generally supportive of these conclusions, but are of uncertain significance because of severe downward drift due to method changes in the National Health And Nutrition Examination Survey III 1988-91 survey. The data analyzed here provide no direct evidence on the matter of whether we are gaining better blood pressure control in hypertensive individuals who really need it.

What is 'nephrosclerosis'? lessons from the US, Japan, and Mexico.

BACKGROUND: Selected features of 'nephrosclerosis' can be quantitated morphometrically in renal histology at autopsy. Specimens are available from Japan, Mexico, and the US (blacks and whites). METHODS: Autopsies of men and women aged 15-79 years provided renal samples for paraffin sectioning. These were assembled in New Orleans for objective evaluation after standardized staining with PAS-Alcian blue and interspersion with each other. Obsolescence of glomeruli, interstitial fibrosis, fibroplastic intimal thickenings of arteries, and arteriolar hyalinization, as operationally defined, were measured by objective morphometry. RESULTS: Obsolescence of glomeruli and interstitial fibrosis displayed the expected correlation with arterial intimal fibroplasia, but failed to confirm any direct association with arteriolar hyalinization. Some of the variation of 'nephrosclerosis', within and between populations, cannot be fully explained by microvascular defects. CONCLUSIONS: Arterial intimal fibroplasia appeared to promote 'nephrosclerosis', in the sense of fibrous replacement of atrophied nephrons, but arteriolar hyalinization did not. Hyaline deposits in arterioles may offer little or no threat to the integrity of the affected nephrons. 'Nephrosclerosis' appears to be multifactorial; it may be, in part, a consequence of fibroplasia in microscopic arteries causing ischaemic injury to scattered nephrons, but may also be a confluence of basically separate conditions, only some of which are known.

Associations of coronary heart disease risk factors with the intermediate lesion of atherosclerosis in youth. The Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group.

The raised fatty streak (fatty plaque) is the gross term for the lesion intermediate between the juvenile (flat) fatty streak and the raised lesion of atherosclerosis. We measured the percentage of intimal surface involved with flat fatty streaks, raised fatty streaks, and raised lesions in the aortas and right coronary arteries of 2876 autopsied persons aged 15 through 34 years who died of external causes. Raised fatty streaks were present in the abdominal aortas of approximately 20% of 15- to 19-year-old subjects, and this percentage increased to approximately 40% for 30- to 34-year-old subjects. Raised fatty streaks were present in the right coronary arteries of approximately 10% of 15- to 19-year-old subjects, and this percentage increased to approximately 30% for 30- to 34-year-old subjects. The percent intimal surface involved with raised fatty streaks increased with age in both arteries and was associated with high non-high density lipoprotein (HDL) and low HDL cholesterol concentrations in the abdominal aorta and right coronary artery, with hypertension in the abdominal aorta, with obesity in the right coronary artery of men, and with impaired glucose tolerance in the right coronary artery. Associations of risk factors with raised fatty streaks became evident in subjects in their late teens, whereas associations of risk factors with raised lesions became evident in subjects aged >25 years. These results are consistent with the putative transitional role of raised fatty streaks and show that coronary heart disease risk factors accelerate atherogenesis in the second decade of life. Thus, long-range prevention of atherosclerosis should begin in childhood or adolescence.

Association of Coronary Heart Disease Risk Factors with microscopic qualities of coronary atherosclerosis in youth.

BACKGROUND: This study examined whether atherosclerosis in young people is associated with the risk factors for clinical coronary heart disease (CHD). Methods and Results-Histological sections of left anterior descending coronary arteries (LADs) from 760 autopsied 15- to 34-year-old victims of accidents, homicides, and suicides were graded according to the American Heart Association (AHA) system and computerized morphometry. Risk factors (dyslipoproteinemia, smoking, hypertension, obesity, impaired glucose tolerance) were assessed by postmortem measurements. Approximately 2% of 15- to 19-year-old men and 20% of 30- to 34-year-old men had AHA grade 4 or 5 (advanced) lesions. No 15- to 19-year-old women had grade 4 or 5 lesions; 8% of 30- to 34-year-old women had such lesions. Approximately 19% of 30- to 34-year-old men and 8% of 30- to 34-year-old women had atherosclerotic stenosis > or =40% in the LAD. AHA grade 2 or 3 lesions (fatty streaks), grade 4 or 5 lesions, and stenosis > or =40% were associated with non-HDL cholesterol > or =4.14 mmol/L (160 mg/dL). AHA grade 2 or 3 lesions were associated with HDL cholesterol <0.91 mmol/L (35 mg/dL) and smoking. AHA grade 4 or 5 lesions were associated with obesity (body mass index > or =30 kg/m(2)) and hypertension (mean arterial pressure > or =110 mm Hg). CONCLUSIONS: -Young Americans have a high prevalence of advanced atherosclerotic coronary artery plaques with qualities indicating vulnerability to rupture. Early atherosclerosis is influenced by the risk factors for clinical CHD. Long-range prevention of CHD must begin in adolescence or young adulthood.

Effects of coronary heart disease risk factors on atherosclerosis of selected regions of the aorta and right coronary artery. PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth.

We examined topographic distributions of atherosclerosis and their relation to risk factors for adult coronary heart disease in right coronary arteries and abdominal aortas of more than 2000 autopsied persons 15 through 34 years of age. We digitized images of Sudan IV-stained fatty streaks and of manually outlined raised lesions and computed the percent surface area involved by each lesion in each of 6 regions of each artery. In abdominal aortas of 15- to 24-year-old persons, fatty streaks involve an elongated oval area on the dorsolateral intimal surface and another oval area in the middle third of the ventral surface. Raised lesions in 25- to 34-year-old persons involve an oval area in the distal third of the dorsolateral intimal surface. In other areas of the abdominal aortas of older persons, fatty streaks occur but raised lesions are rare. In the right coronary arteries of 15- to 24-year-old persons, fatty streaks are most frequent on the myocardial aspect of the first 2 cm. Raised lesions follow a similar pattern in 25- to 34-year-old persons. High non-HDL cholesterol and low HDL cholesterol concentrations are associated with more extensive fatty streaks and raised lesions in all regions of both arteries. Smoking is associated with more extensive fatty streaks and raised lesions of the abdominal aorta, particularly in the dorsolateral region of the distal third of the abdominal aorta. Hypertension is not associated with fatty streaks in whites or blacks but is associated with more extensive raised lesions in blacks. Risk factor effects on arterial regions that are vulnerable to lesions are approximately 25% greater than risk factor effects assessed over entire arterial segments. These risk factor effects on vulnerable sites emphasize the need for risk factor control during adolescence and young adulthood to prevent or delay the progression of atherosclerosis.

The heterogeneity of vascular findings in the kidneys of patients with benign essential hypertension.

As the interlobular arteries of the ageing kidney progressively accumulate intimal fibroplasia, these fibroplastic changes appear to introduce strictures upon the interlobular arteries. These strictures are expected to generate nephron heterogeneity, which is a uniquely disturbed setting peculiarly suited to sustaining both high and low renin forms of hypertension. Fibroplastic renovasculopathy accumulates with age at varying rates in different human populations, and these rates closely parallel the rise of blood pressure with age, as documented by community surveys. Here, I introduce the expression type 1 for hypertension in subjects with mild or minimal renovasculopathy, and type 2 for those with severe vasculopathy. Data reviewed here imply that variations in prevailing blood pressure levels between populations can be attributed entirely, or almost entirely, to type 2 hypertension. No practical test is available to detect nephron heterogeneity clinically. Tests for this purpose have not been and are not now in development. The reason for this deficiency is probably the general lack of suspicion regarding the existence of this pathological entity. Once the entity becomes the target of attention, a variety of tests for measuring its severity in clinical patients should follow readily.

Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study.

CONTEXT: Atherosclerosis, the underlying cause of coronary heart disease, has been shown to be present even in young adults. OBJECTIVE: To document the extent and severity of atherosclerosis in adolescents and young adults in the United States. DESIGN AND SETTING: The Pathobiological Determinants of Atherosclerosis in Youth Study, a multi-institutional autopsy study conducted in US medical centers. Subjects A total of 2876 study subjects, between 15 and 34 years old, black and white, men and women, who died of external causes and underwent autopsy between June 1, 1987, and August 31, 1994. MAIN OUTCOME MEASURES: Extent, prevalence, and topography of atherosclerotic lesions. RESULTS: Intimal lesions appeared in all the aortas and more than half of the right coronary arteries of the youngest age group (15-19 years) and increased in prevalence and extent with age through the oldest age group (30-34 years). Fatty streaks were more extensive in black subjects than in white subjects, but raised lesions did not differ between blacks and whites. Raised lesions in the aortas of women and men were similar, but raised lesions in the right coronary arteries of women were less than those of men. The prevalence of total lesions was lower in the right coronary artery than in the aorta, but the proportion of raised lesions among total lesions was higher in the right coronary artery than in the aorta. CONCLUSIONS: Atherosclerosis begins in youth. Fatty streaks and clinically significant raised lesions increase rapidly in prevalence and extent during the 15- to 34-year age span. Primary prevention of atherosclerosis, as contrasted with primary prevention of clinically manifest atherosclerotic disease, must begin in childhood or adolescence.

Renovasculopathies of hypertension in Hispanic residents of Dallas, Texas.

BACKGROUND: Mean blood pressure levels (MBP) appear to rise with age slowly in the population of Mexico City and more swiftly in the U.S. in the black and white population, judging from published survey data. Some evidence suggests that MBP rises at intermediate rates in Hispanics in the U.S. METHOD: This question is explored here in two ways, by review of published survey data and by a novel approach that uses renal tissues obtained from forensic autopsies to estimate MBP. Past studies have revealed good agreement between the two methods of estimating MBP. RESULTS: Good agreement is again observed from the results of this study. Results from both methods agree that MBP is much lower at all ages in Mexican men and women than in blacks and whites in the U.S. Both methods also agree that Hispanics in the U.S. demonstrate an intermediate rise in MBP. A speculative first look at a small sample of U.S. Hispanics suggest that MBP rates of recent immigrants tend to resemble those of Mexico, while MBP levels of migrants of long-term residence resemble the native-born U.S. populations. CONCLUSIONS: The findings underscore the need for definitive testing to confirm if Mexicans who relocate to the U.S. may acquire an acceleration of the renovasculopathies, and of the lifelong progression toward hypertension that this implies.

Salt, obesity, and alcohol fail to induce a lasting rise of blood pressure with age, and may be independent of renocortical vasculopathy.

Essential hypertension has a multitude of aetiologies, environmental circumstances that impact harmfully upon blood pressure levels. These aetiologies fall into two types: a reversible type that requires continuous exposure to the inciting agent to sustain the elevated blood pressure, and a persistent type which introduces some form of permanent change, presumably in body tissues. Available data on salt overload, obesity, and alcohol tend to cast these agents as reversible, without persistent effects. Agents of the reversible type emerge here as unlikely candidates for explaining the rise of blood pressure with age. Evidence reviewed here implicates intimal fibroplasia in renocortical arteries as the accumulated record that causes rising of blood pressure with age by Goldblatt mechanisms actuated through nephron heterogeneity. Such mechanisms could explain the persistent effects that propel the rise of blood pressure with age at varying rates among world-wide populations. These findings offer a new starting place for efforts to discover the aetiological agents that propel the rise of blood pressure with age, agents that apparently do not include salt, obesity, or alcohol.

Histologic characteristics of coronary artery in relation to the renovasculopathies of hypertension.

Coronary heart disease is a consequence of prior conditions in the coronary artery that invariably include atherosclerotic plaques with necrotic core. Evidence indicates that atheronecrosis is itself a late outcome of certain precursor conditions in the arteries, especially low density of intimal smooth muscle cells and extensive foam cell infiltration. A sequential process is indicated: the defined precursors set the conditions, atheronecrosis appears, and from this coronary heart disease eventually emerges. Hypertensive kidneys typically manifest intimal fibroplasia of cortical arteries and hyalinization of arterioles. Both forms of renovasculopathy, fibroplastic and hyaline, correlate with the early development of atheronecrosis and its precursor conditions. Hyalinization of renal arterioles, however, especially marks subjects with the greatest risk of further developing heart disease. These findings suggest an important prognostic significance to the finding of hyaline deposits in renocortical arterioles; the affected patient may be at exceptionally high risk for coronary heart disease. Results are derived from a series of forensic autopsies, in which morphometric assessment of paraffin sections of coronary arteries and renal cortex was performed.

Medial thickness of coronary arteries as a correlate of atherosclerosis.

As coronary arteries grow older, they tend to acquire fibroplastic intimal thickenings. Those aging arteries that manifest the greatest fibroplasia are typically the ones that acquire atherosclerotic plaques with necrotic cores (YesA arteries); this is especially so if foam cell infiltration is also extensive. The present study finds that thicker media also distinguishes YesA from NoA specimens. Coronary arteries obtained at autopsy from males and females in eight populations, 16 groups altogether, were evaluated histologically for the YesA characteristics: intimal fibroplasia, foam cell infiltration, and medial thickness. The rankings of the 16 groups at ages 15-29 years persisted significantly into ages 30-69 years when looking at intimal fibroplasia, but not at foam cell infiltration. Medial thickness also yielded youthful population rankings that persisted into older groups, and the rankings were similar to those based on fibroplasia. Virtually all important correlations were obscured if intima:media ratios were employed, because the top and bottom numbers in the ratio typically move in parallel with each other across the meaningful group comparisons, thereby canceling each other.