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Biomedical subjects

Stanley S Franklin

Publications and source records attributed to Stanley S Franklin.

At least 19 recordsLinked to original sources

Relation between renal function within the normal range and central and peripheral arterial stiffness in hypertension.

Chronic kidney disease is accompanied by increased large-artery stiffness, but the relation between glomerular filtration rate within the reference range and central or peripheral arterial stiffness has been understudied. The link between renal function and arterial stiffness was assessed in 305 patients with never-treated essential hypertension (men: 58%; age: 48+/-11 years, blood pressure: 151/95+/-20/11 mm Hg), free from overt cardiovascular disease and with serum creatinine values <1.4 mg/dL (men) and <1.2 mg/dL (women), who underwent noninvasive aortic and upper-limb pulse wave velocity (PWV) determination. Aortic PWV was strongly related to age (r=0.55; P<0.001), whereas upper-limb PWV had a weaker nonlinear relation with age (beta=1.392; P<0.001 for age; beta=-1.312; P<0.001 for age squared) and a weak relation with aortic PWV (r=0.22; P<0.001). Glomerular filtration rate (GFR), estimated according to the Mayo clinic equation for healthy subjects, was inversely correlated with large-artery stiffness, as assessed by aortic PWV (r=-0.34; P<0.001), and with peripheral artery stiffness, as assessed by upper-limb PWV (r=-0.25; P<0.001). In a multivariate linear regression, aortic PWV was independently predicted by age (beta=0.48; P<0.001), mean arterial pressure (beta=0.14; P=0.013), and GFR (beta=-0.13, P=0.029). Upper-limb PWV was predicted by GFR (beta=-0.24; P<0.001) and mean arterial pressure (beta=0.20; P<0.001). We conclude that, in hypertensive patients with normal renal function, an inverse relationship exists between GFR and stiffness of both central elastic and peripheral muscular arteries. These relations are in part independent from the effect of several confounders, including age, sex, and blood pressure values.

Adult↗

Blood pressure categories, hypertensive subtypes, and the metabolic syndrome.

BACKGROUND: Elevated blood pressure (BP) is one element of metabolic syndrome (MetS); however, the relation of various BP categories and hypertension subtypes to the likelihood of having MetS is not well defined. METHODS: We determined the odds of MetS, defined by the National Cholesterol Education Program, in various BP categories from a cross-sectional study of 5968 individuals aged at least 18 years and untreated for hypertension (weighted to 124.7 million) in the National Health and Nutrition Examination Survey, 1999-2002. Nonhypertensive BP categories were optimal, normal, and high-normal BP, according to JNC-VI classification. Hypertension consisted of three subtypes: isolated diastolic hypertension (IDH), systolic-diastolic hypertension (SDH), and isolated systolic hypertension (ISH). RESULTS: Among those with hypertension and MetS, 25.3% had IDH, 20.2% had SDH, and 54.5% had ISH. The MetS prevalence in nontreated persons was 5.8% for optimal BP, 9.1% for normal BP, 38.2% for high-normal BP, 45.9% for IDH, 44.3% for SDH, and 43.9% for ISH. Risk factor odds ratios (95% confidence intervals; reference group, optimal BP), adjusted for age, sex, total cholesterol, and smoking, were 1.6 (1.2-2.2) for normal BP, 9.4 (6.9-12.7) for high-normal BP, 14.7 (8.9-24.0) for IDH, 12.2 (7.2-20.8) for SDH, and 10.2 (7.0-14.9) for ISH (all P < 0.01); odds ratios were higher for women in all categories. CONCLUSIONS: Despite having the lowest mean age, IDH subtype is associated with greatest likelihood of MetS. The high frequency of ISH in the hypertensive population, however, makes ISH the most common hypertensive subtype in persons with MetS.

Adult↗

Hypertension in older people: part 1.

Once considered part of the normal aging process, the development of isolated systolic hypertension represents a late manifestation of increased arterial stiffness in older people. Furthermore, isolated systolic hypertension is the single most frequent subtype of hypertension in the US adult population. Indeed, central arterial stiffness rather than peripheral vascular resistance becomes the dominant hemodynamic factor in both normotensive and hypertensive individuals after the age of 50-60 years. Stiffening disease, an age-related degeneration of the elastic elements of the thoracic aorta, is associated with a widening of brachial pulse pressure. Brachial pulse pressure predicts future cardiovascular disease events. However, pressure wave amplification produces higher brachial than aortic pressures and, therefore, central rather than peripheral blood pressure indices are more reliable measures of cardiovascular risk. Stiffening disease of aging is accompanied by early wave reflection, which results in a significant augmentation of central systolic pressure in late systole and further adds to increased cardiac afterload--so-called ventricular-vascular uncoupling. Diabetes, impaired renal function, and untreated or poorly treated hypertension may lead to premature arterial stiffening; its consequences are stiffening and hypertrophy of the left ventricle and predisposition to coronary heart disease, heart failure, stroke, vascular dementia, and chronic kidney disease.

Adult↗

Hypertension in older people: part 2.

There is overwhelming evidence that pharmacologic treatment of isolated systolic hypertension (ISH) (systolic blood pressure >or=140 mm Hg and diastolic blood pressure <90 mm Hg) reduces cardiovascular events and extends longevity in the elderly; in the very old (80 years or older), the evidence supports decreased incident stroke and heart failure, but is less convincing in terms of longevity. Thus, the inherent increased risk for ISH vascular events highlights the importance of its control. Importantly, ISH in the elderly, primarily related to large artery stiffness, remains more difficult to control than diastolic hypertension in the young, which is primarily related to increased peripheral vascular resistance. Appropriate lifestyle and pharmacologic intervention is indicated in individuals with systolic blood pressure >or=140 mm Hg in general and >or=130 mm Hg in persons with diabetes or chronic kidney disease. Lifestyle intervention may reduce the need for extensive antihypertensive therapy and minimize associated cardiovascular risk factors. To date, only a small percentage of older ISH patients are being treated to goal. Reaching target systolic blood pressure levels most often requires the use of polypharmacy that includes a diuretic and perhaps specific agents that target arterial stiffness and early wave reflection.

Aged↗

Efficacy and safety of irbesartan/HCTZ combination therapy as initial treatment for rapid control of severe hypertension.

Severe hypertension is difficult to control. This prospective, randomized, double-blind, active-controlled, multicenter trial compared efficacy and safety of once-daily irbesartan/hydrochlorothiazide (HCTZ) combination therapy with irbesartan monotherapy in severe hypertension. Patients who were untreated or uncontrolled on monotherapy (seated diastolic blood pressure [BP] > or =110 mm Hg) received fixed-dose irbesartan 150 mg/HCTZ 12.5 mg combination therapy for 7 weeks, force-titrated to irbesartan 300 mg/HCTZ 25 mg at week 1 (n=468); or irbesartan 150 mg monotherapy, force-titrated to 300 mg at week 1 (n=269). Significantly more patients on combination therapy achieved seated diastolic BP <90 mm Hg at week 5 (primary end point) compared with monotherapy recipients (47.2% vs 33.2%; P=.0005). Likewise, significantly more patients attained goals per the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) (<140/90 mm Hg) at week 5 (34.6% vs 19.2%, respectively; P<.0001), while the mean difference between combination and monotherapy in seated diastolic BP and seated systolic BP was 4.7 mm Hg and 9.7 mm Hg (P<.0001). Greater and more rapid BP reduction with irbesartan/HCTZ was achieved without additional side effects.

Adult↗

Impact of C-reactive protein on the likelihood of peripheral arterial disease in United States adults with the metabolic syndrome, diabetes mellitus, and preexisting cardiovascular disease.

We sought to determine, in United States (US) patients with the metabolic syndrome (MS), diabetes mellitus (DM), or preexisting cardiovascular disease, whether higher levels of C-reactive protein (CRP) would identify those with an increased likelihood of peripheral arterial disease (PAD). In a cross-sectional evaluation of the National Health and Nutrition Examination Survey (NHANES), 1999 to 2000, of 1,600 adults (representing a US population of 62.9 million) aged > or =40 years who had valid ankle-brachial index measurements available, subjects were categorized as having MS (without DM), DM, preexisting cardiovascular disease, or none of these conditions. The presence of PAD was defined as an ankle-brachial index <0.9. Subjects were also divided into groups according to CRP levels that were low (<1 mg/L), intermediate (1 to 3 mg/L), and elevated (>3.0 mg/L). Weighted multiple logistic regression analysis examined the odds of PAD by CRP group and disease category compared with the reference group of subjects who did not have MS, DM, or cardiovascular disease and had a CRP level of <1 mg/L. Those with MS (including DM) had an increased likelihood of PAD (odds ratio 4.8, 95% confidence interval 1.4 to 16.1, p = 0.01) as did those with MS without diabetes and an elevated CRP level (odds ratio 3.9, 95% confidence interval 1.1 to 14.6, p = 0.04); those with DM and an elevated CRP had the highest likelihood of PAD (odds ratio 8.6, 95% confidence interval 2.2 to 34.0, p = 0.001). In conclusion, the likelihood of PAD in US adults with MS and DM is enhanced by elevated CRP levels.

Adult↗

Cardiovascular morbidity and mortality in hypertensive patients with lower versus higher risk: a LIFE substudy.

We hypothesized that losartan was superior to atenolol in reducing cardiovascular events in a lower-risk group (LRG) versus a higher-risk group (HRG) of patients in a Losartan Intervention For Endpoint reduction (LIFE) substudy, independently of blood pressure (BP) reduction. In a post hoc analysis, we designated 4282 patients as LRG on the basis of: (1) no previous cardiovascular disease (coronary, cerebral, peripheral vascular disease); (2) no diabetes; (3) no isolated systolic hypertension; and (4) inclusion of the lowest 3 quartiles of electrocardiographically documented left ventricular hypertrophy. The HRG consisted of 4911 remaining patients who did not qualify for the LRG. In the LRG, losartan was superior to atenolol in reducing stroke: hazard ratio (HR), 0.72 (95% confidence interval [CI], 0.53 to 0.98); new-onset diabetes (HR, 0.74 [95% CI, 0.58 to 0.93]; and new-onset atrial fibrillation: HR, 0.69 (95% CI, 0.51 to 0.92), all P<0.05 but not composite end points or cardiovascular mortality (both P=NS). In the HRG, losartan was superior to atenolol in reducing composite end points: HR, 0.82 (95% CI, 0.71 to 0.94), P<0.01; cardiovascular mortality: HR, 0.77 (95% CI, 0.62 to 0.95), P<0.05; stroke: HR, 0.75 (95% CI, 0.61 to 0.92), P<0.01; new-onset diabetes: HR, 0.76 (95% CI, 0.60 to 0.96), P<0.05; and new-onset atrial fibrillation: HR, 0.71 (95% CI, 0.58 to 88), P<0.05. Test for interaction of treatment with LRG versus HRG was not significant for composite end point, stroke, or atrial fibrillation, but was for cardiovascular mortality (P=0.018). Achieved systolic BP reduction favored losartan over atenolol by -1.8 mm Hg in LRG (P=NS) and -0.7 mm Hg (P=0.001) in HRG, but no significant differences occurred in diastolic or mean BP in either group. In conclusion, losartan compared with atenolol reduces the risk of stroke, new-onset diabetes, and new-onset atrial fibrillation in the LRG and the HRG.

Adrenergic beta-Antagonists↗

Metabolic syndrome is associated with aortic stiffness in untreated essential hypertension.

Metabolic syndrome is a powerful predictor of cardiovascular disease in hypertension, and large-artery stiffness is increasingly recognized as a cardiovascular risk factor. We hypothesized that the adverse prognostic significance of the metabolic syndrome in hypertension might be explained in part by its association with aortic stiffness. A total of 169 newly diagnosed, never treated, nondiabetic patients with essential hypertension (men 55%, 48+/-11 years) were classified by the presence (n=45) or absence (n=124) of the metabolic syndrome. All patients underwent aortic and upper limb pulse wave velocity determination by means of an applanation tonometry-based method. Aortic pulse wave velocity had a direct correlation with office and 24-hour systolic pressure (r=0.42 and 0.31, respectively), as well as with waist circumference (r=0.35, all P<0.001), but not with body mass index (r=0.10, P=not significant). Aortic pulse wave velocity was higher in the subgroup with the metabolic syndrome (10.0+/-2.7 versus 8.8+/-2.1 m/s; P=0.003), whereas upper limb velocity did not differ in the 2 groups (8.6+/-1.4 versus 8.7+/-1.5 m/s; P=not significant). In a multiple regression, aortic pulse wave velocity was independently associated with age, systolic blood pressure, and the metabolic syndrome. Only diastolic BP independently predicted upper limb pulse wave velocity. We conclude that in untreated hypertension, the metabolic syndrome is independently associated with a higher aortic, but not upper limb, pulse wave velocity. Central, but not general, adiposity is an important determinant of aortic stiffness in hypertension.

Abdomen↗

Systolic and diastolic blood pressure lowering as determinants of cardiovascular outcome.

Based on individual patient data, we performed a quantitative overview of trials in hypertension to investigate to what extent lowering of systolic blood pressure (SBP) and diastolic blood pressure (DBP) contributed to cardiovascular prevention. We selected trials that tested active antihypertensive drugs against placebo or no treatment. Our analyses included 12,903 young (30 to 49 years of age) patients randomized in 3 trials and 14,324 old (60 to 79 years of age) and 1209 very old (> or =80 years of age) patients enrolled in 8 trials. Antihypertensive treatment reduced SBP/DBP by 8.3/4.6 mm Hg in young patients, by 10.7/4.2 mm Hg in old patients, and by 9.4/3.2 mm Hg in very old patients, respectively, resulting in ratios of DBP to SBP lowering of 0.55, 0.39, and 0.32, respectively (P=0.004 for trend with age). In spite of the differential lowering of SBP and DBP, antihypertensive treatment reduced the risk of all cardiovascular events, stroke and myocardial infarction in the 3 age strata to a similar extent. Absolute benefit increased with age and with lower ratio of DBP to SBP lowering. Furthermore, in patients with a larger-than-median reduction in SBP, active treatment consistently reduced the risk of all outcomes irrespective of the decrease in DBP or the achieved DBP. These findings remained consistent if the achieved DBP averaged <70 mm Hg. In conclusion, our overview suggests that antihypertensive drug treatment improves outcome mainly through lowering of SBP.

Antihypertensive Agents↗

Predictors of new-onset diastolic and systolic hypertension: the Framingham Heart Study.

BACKGROUND: Factors leading differentially to the development of isolated diastolic (IDH), systolic-diastolic (SDH), and isolated systolic (ISH) hypertension are poorly understood. We examined the relations of blood pressure (BP) and clinical risk factors to the new onset of the 3 forms of hypertension. METHODS AND RESULTS: Participants in the Framingham Heart Study were included if they had undergone 2 biennial examinations between 1953 and 1957 and were free of antihypertensive therapy and cardiovascular disease. Compared with optimal BP (SBP <120 and DBP <80 mm Hg), the adjusted hazard ratios (HRs) for developing new-onset IDH over the ensuing 10 years were 2.75 for normal BP, 3.29 for high-normal BP (both P<0.0001), 1.31 (P=0.40) for SDH, and 0.61 (P=0.36) for ISH. The HRs of developing new-onset SDH were 3.32, 7.96, 7.10, and 23.12 for the normal BP, high-normal BP, ISH, and IDH groups, respectively (all P<0.0001). The HRs of developing ISH were 3.26 for normal and 4.82 for high-normal BP (both P<0.0001), 1.39 (P=0.24) for IDH, and 1.69 (P<0.01) for SDH. Increased body mass index (BMI) during follow-up predicted new-onset IDH and SDH. Other predictors of IDH were younger age, male sex, and BMI at baseline. Predictors of ISH included older age, female sex, and increased BMI during follow-up. CONCLUSIONS: Given the propensity for increased baseline BMI and weight gain to predict new-onset IDH and the high probability of IDH to transition to SDH, it is likely that IDH is not a benign condition. ISH arises more commonly from normal and high-normal BP than from "burned-out" diastolic hypertension.

Adult↗

Increased stroke volume and aortic stiffness contribute to isolated systolic hypertension in young adults.

Isolated systolic hypertension is a common condition in individuals aged older than 60 years. However, isolated systolic hypertension has also been described in young individuals, although the mechanisms are poorly understood. We hypothesized that in young adults, isolated systolic hypertension and essential hypertension have different hemodynamic mechanisms and the aim of this study was to test this hypothesis in a cohort of subjects from The ENIGMA Study. Peripheral and central blood pressure, aortic pulse wave velocity, cardiac output, stroke volume, and peripheral vascular resistance were determined in 1008 subjects, aged 17 to 27 years. Compared with normotensive subjects, those with isolated systolic hypertension had significantly higher peripheral, central, and mean blood pressure, aortic pulse wave velocity, cardiac output, and stroke volume (P<0.001 for all comparisons). However, there were no differences in pulse pressure amplification, heart rate, or peripheral vascular resistance between the two groups. Compared with subjects with essential hypertension, mean pressure, heart rate, and peripheral vascular resistance were all significantly lower in isolated systolic hypertensive subjects, but pulse pressure amplification, aortic pulse wave velocity, cardiac output, and stroke volume were higher (P<0.001 for all comparisons). We have demonstrated that in young adults, isolated systolic hypertension and essential hypertension arise from different hemodynamic mechanisms. Isolated systolic hypertension appears to result from an increased stroke volume and/or aortic stiffness, whereas the major hemodynamic abnormality underlying essential hypertension is an increased peripheral vascular resistance. Long-term follow-up of these individuals is now required to determine whether they are at increased risk compared with age-matched normotensive individuals.

Adolescent↗

Impact of the metabolic syndrome on mortality from coronary heart disease, cardiovascular disease, and all causes in United States adults.

BACKGROUND: Mortality resulting from coronary heart disease (CHD), cardiovascular disease (CVD), and all causes in persons with diabetes and pre-existing CVD is high; however, these risks compared with those with metabolic syndrome (MetS) are unclear. We examined the impact of MetS on CHD, CVD, and overall mortality among US adults. METHODS AND RESULTS: In a prospective cohort study, 6255 subjects 30 to 75 years of age (54% female) (representative of 64 million adults in the United States) from the Second National Health and Nutrition Examination Survey were followed for a mean+/-SD of 13.3+/-3.8 years. MetS was defined by modified National Cholesterol Education Program criteria. From sample-weighted multivariable Cox proportional-hazards regression, compared with those with neither MetS nor prior CVD, age-, gender-, and risk factor-adjusted hazard ratios (HRs) for CHD mortality were 2.02 (95% CI, 1.42 to 2.89) for those with MetS and 4.19 (95% CI, 3.04 to 5.79) for those with pre-existing CVD. For CVD mortality, HRs were 1.82 (95% CI, 1.40 to 2.37) and 3.14 (95% CI, 2.49 to 3.96), respectively; for overall mortality, HRs were 1.40 (95% CI, 1.19 to 1.66) and 1.87 (95% CI, 1.60 to 2.17), respectively. In persons with MetS but without diabetes, risks of CHD and CVD mortality remained elevated. Diabetes predicted all mortality end points. Those with even 1 to 2 MetS risk factors were at increased risk for mortality from CHD and CVD. Moreover, MetS more strongly predicts CHD, CVD, and total mortality than its individual components. CONCLUSIONS: CHD, CVD, and total mortality are significantly higher in US adults with than in those without MetS.

Adult↗

Systolic blood pressure: it's time to take control.

Once considered an inconsequential part of the aging process, an age-associated rise in systolic blood pressure (SBP) occurs as a consequence of increased arterial stiffness and contributes to a high prevalence of systolic hypertension after middle-age. Elevated SBP imparts a predilection toward the onset of vascular events, highlighting the importance of its control. Current philosophy ranks systolic pressure as the most relevant component of blood pressure (BP) for determining risk for cardiovascular and other events in hypertensive patients, particularly those >50 years of age. Despite its prognostic role, SBP remains more difficult to control than diastolic BP (DBP), and most middle-age and older hypertensive patients fail to achieve recommended targets. In part, the lack of strict control of SBP in the more aged population lies in the physiology of hypertension. Younger persons tend toward isolated diastolic hypertension or combined systolic-diastolic hypertension, primarily driven by increased peripheral resistance and more effectively treated by antihypertensive medications; whereas older persons develop isolated systolic hypertension (ISH) associated with increased arterial stiffness that appears to be less amenable to current therapies. Thus, diastolic pressure in hypertensive patients often plateaus as patients reach middle-age and subsequently declines, whereas systolic pressure consistently rises through the ensuing decades. Treatment approaches favoring control of DBP frequently result in residual high SBP, putting patients at greater risk for vascular complications. Improving patient outcomes relies on antihypertensive therapy that appropriately addresses control of SBP and pulse pressure, underscoring the importance of therapeutic options that effectively reduce arterial stiffness.

Age Factors↗