Author
Scott M. Grundy
Other affiliations: University of California, San Francisco, University of California, Davis, National Institutes of Health ...read more
Bio: Scott M. Grundy is an academic researcher from University of Texas Southwestern Medical Center. The author has contributed to research in topics: Cholesterol & Lipoprotein. The author has an hindex of 187, co-authored 841 publications receiving 231821 citations. Previous affiliations of Scott M. Grundy include University of California, San Francisco & University of California, Davis.
Papers published on a yearly basis
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TL;DR: It is indicated that healthy young sons of fathers with established coronary artery disease have a greater postprandial triglyceride response than do sons of dads without this disease, and this finding appears to be the result of a carefully conducted study.
Abstract: In this issue, the report by Uiterwaal and colleagues [1] indicates that healthy young sons of fathers with established coronary artery disease have a greater postprandial triglyceride response than do sons of fathers without this disease. This finding appears to be the result of a carefully conducted study, and although the difference in responses between the two groups is not great, it is statistically significant. Two alternative explanations could account for the difference in response in the two types of offspring: The difference could be either acquired or genetic. Both possibilities must be considered. An acquired difference might be one of two kinds. First, sons may have acquired habits from their fathers before their fathers developed coronary artery disease. For example, they might have acquired their fathers' eating and exercise habits or attitudes toward work and stress. Although no definite evidence was obtained about these acquired habits, they could be subtle and difficult to detect without more extensive testing. If present, they could have affected the postprandial triglyceride response. A second possibility is that sons were psychologically affected by their fathers' heart attacks and consequently these sons modified their behavior in an attempt to decrease their own risk. This is a strong possibility. We know that having a myocardial infarction is a strong motivating factor for changes in lifestyle (for example, stopping smoking and changing the diet) in affected patients, and some of this motivation probably rubs off on their offspring. An example of this effect is the lower fat intake in sons of fathers with coronary artery disease when compared with sons in the control group. A low-fat diet could induce an increased postprandial response by slightly increasing fasting triglyceride concentrations. This was not detected in the study by Uiterwaal and colleagues, but larger studies have shown that lower-fat diets increase triglyceride levels. Such an effect, therefore, cannot be excluded. The alternative mechanism contributing to a difference in postprandial triglyceride response is a genetic difference, either monogenic or polygenic. If parents were heterozygous for a monogenic disorder of triglyceride metabolism, only half the sons should have inherited the defect; thus, only half would have shown an excessive response. Of course, the response in affected sons would have been bimodal. This possibility is not mentioned in Uiterwaal and colleagues' study, but it should have been examined. All affected parents certainly were not heterozygous for a monogenic defect in triglyceride metabolism. Thus, if a monogenic defect exists that affects triglyceride metabolism, it must have been much more marked in a few sons to make the average response statistically significant. It should have been relatively easy to identify such sons, but this was not done in Uiterwaal and colleagues' study. The second alternative is that an increased postprandial response is polygenic. For example, fathers with coronary artery disease had higher levels of total cholesterol and low-density lipoprotein (LDL) cholesterol than did control fathers, and, on the average, they had polygenic hypercholesterolemia. It is interesting to note that this polygenic phenotype was diluted out in the sons or had not yet become manifest; sons of fathers with coronary artery disease did not have higher total cholesterol and LDL levels than did control sons. Perhaps it is possible that fathers with coronary artery disease had polygenic postprandial hypertriglyceridemia, and enough abnormal genes, albeit diluted by one half, were transmitted to allow this trait to be observed in their sons. Fathers with coronary artery disease certainly had higher fasting triglyceride levels than did control fathers, and therefore they very possibly could have had polygenic hypertriglyceridemia. Consequently, some of the hypertriglyceridemic genes may have been transmitted to their sons. If so, what are some of these abnormal genes? They could have been a host of different genes affecting triglyceride and lipoprotein metabolism, such as those controlling hepatic lipid regulation; lipoprotein lipase; apolipoproteins B, Es, Cs, and As; and LDL receptors, to mention only a few. Increasing evidence suggests that inheritance of a constellation of genes having particular patterns of genetic variation can lead to mild to moderate dyslipidemia, which in turn predisposes to premature coronary artery disease. Because fathers with coronary artery disease definitely had a polygenic form of dyslipidemia, some of the abnormal genes undoubtedly were transmitted to their sons. Thus, findings in this study are compatible with the concept that genetic factors contribute to the mild to moderate dyslipidemia found in patients with premature coronary artery disease. It must be remembered, however, that a confounding effect of acquired characteristics cannot be excluded, which may have contributed to the postprandial responses noted in Uiterwaal and colleagues' study. Does an increased postprandial response mean that increased levels of triglycerides are a risk factor for coronary artery disease? The evidence relating triglycerides to risk for coronary artery disease is complex, and there is not universal agreement on the meaning of this evidence. In my view, available data indicate that increased levels of triglycerides have an atherogenic effect, but this effect may be mediated through other mechanisms (for example, the presence of very-low-density lipoprotein remnants, small LDL particles, decreased levels of high-density lipoprotein cholesterol, and a thrombogenic tendency) [2]. This study sheds little light on the mechanisms involved. Nonetheless, the results are consistent with the possibility that triglyceride-rich lipoproteins have atherogenic potential. This assumes that the entire effect is not explained by modified behavior in sons after their fathers developed clinical evidence of coronary artery disease.
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TL;DR: There is, I think, something ethereal about i —the square root of minus one, which seems an odd beast at that time—an intruder hovering on the edge of reality.
Abstract: There is, I think, something ethereal about i —the square root of minus one. I remember first hearing about it at school. It seemed an odd beast at that time—an intruder hovering on the edge of reality.
Usually familiarity dulls this sense of the bizarre, but in the case of i it was the reverse: over the years the sense of its surreal nature intensified. It seemed that it was impossible to write mathematics that described the real world in …
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Boston University1, Rush University Medical Center2, University of Tennessee Health Science Center3, University of Michigan4, University at Buffalo5, University of Mississippi6, University of Miami7, University of Alabama at Birmingham8, Case Western Reserve University9, National Institutes of Health10
TL;DR: The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated, and empathy builds trust and is a potent motivator.
Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection,
Evaluation, and Treatment of High Blood Pressure" provides a new guideline
for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of
more than 140 mm Hg is a much more important cardiovascular disease
(CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75
mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive
at 55 years of age have a 90% lifetime risk for developing hypertension; (3)
Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80
to 89 mm Hg should be considered as prehypertensive and require health-promoting
lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should
be used in drug treatment for most patients with uncomplicated hypertension,
either alone or combined with drugs from other classes. Certain high-risk
conditions are compelling indications for the initial use of other antihypertensive
drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor
blockers, β-blockers, calcium channel blockers); (5) Most patients with
hypertension will require 2 or more antihypertensive medications to achieve
goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes
or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal
BP, consideration should be given to initiating therapy with 2 agents, 1 of
which usually should be a thiazide-type diuretic; and (7) The most effective
therapy prescribed by the most careful clinician will control hypertension
only if patients are motivated. Motivation improves when patients have positive
experiences with and trust in the clinician. Empathy builds trust and is a
potent motivator. Finally, in presenting these guidelines, the committee recognizes
that the responsible physician's judgment remains paramount.
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TL;DR: In those older than age 50, systolic blood pressure of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP, and hypertension will be controlled only if patients are motivated to stay on their treatment plan.
Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.
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TL;DR: In this article, a randomized controlled trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly people was presented. But the authors did not discuss the effect of the combination therapy in patients living with systolic hypertension.
Abstract: ABCD
: Appropriate Blood pressure Control in Diabetes
ABI
: ankle–brachial index
ABPM
: ambulatory blood pressure monitoring
ACCESS
: Acute Candesartan Cilexetil Therapy in Stroke Survival
ACCOMPLISH
: Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension
ACCORD
: Action to Control Cardiovascular Risk in Diabetes
ACE
: angiotensin-converting enzyme
ACTIVE I
: Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events
ADVANCE
: Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation
AHEAD
: Action for HEAlth in Diabetes
ALLHAT
: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack
ALTITUDE
: ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints
ANTIPAF
: ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation
APOLLO
: A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People
ARB
: angiotensin receptor blocker
ARIC
: Atherosclerosis Risk In Communities
ARR
: aldosterone renin ratio
ASCOT
: Anglo-Scandinavian Cardiac Outcomes Trial
ASCOT-LLA
: Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm
ASTRAL
: Angioplasty and STenting for Renal Artery Lesions
A-V
: atrioventricular
BB
: beta-blocker
BMI
: body mass index
BP
: blood pressure
BSA
: body surface area
CA
: calcium antagonist
CABG
: coronary artery bypass graft
CAPPP
: CAPtopril Prevention Project
CAPRAF
: CAndesartan in the Prevention of Relapsing Atrial Fibrillation
CHD
: coronary heart disease
CHHIPS
: Controlling Hypertension and Hypertension Immediately Post-Stroke
CKD
: chronic kidney disease
CKD-EPI
: Chronic Kidney Disease—EPIdemiology collaboration
CONVINCE
: Controlled ONset Verapamil INvestigation of CV Endpoints
CT
: computed tomography
CV
: cardiovascular
CVD
: cardiovascular disease
D
: diuretic
DASH
: Dietary Approaches to Stop Hypertension
DBP
: diastolic blood pressure
DCCT
: Diabetes Control and Complications Study
DIRECT
: DIabetic REtinopathy Candesartan Trials
DM
: diabetes mellitus
DPP-4
: dipeptidyl peptidase 4
EAS
: European Atherosclerosis Society
EASD
: European Association for the Study of Diabetes
ECG
: electrocardiogram
EF
: ejection fraction
eGFR
: estimated glomerular filtration rate
ELSA
: European Lacidipine Study on Atherosclerosis
ESC
: European Society of Cardiology
ESH
: European Society of Hypertension
ESRD
: end-stage renal disease
EXPLOR
: Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination
FDA
: U.S. Food and Drug Administration
FEVER
: Felodipine EVent Reduction study
GISSI-AF
: Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation
HbA1c
: glycated haemoglobin
HBPM
: home blood pressure monitoring
HOPE
: Heart Outcomes Prevention Evaluation
HOT
: Hypertension Optimal Treatment
HRT
: hormone replacement therapy
HT
: hypertension
HYVET
: HYpertension in the Very Elderly Trial
IMT
: intima-media thickness
I-PRESERVE
: Irbesartan in Heart Failure with Preserved Systolic Function
INTERHEART
: Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries
INVEST
: INternational VErapamil SR/T Trandolapril
ISH
: Isolated systolic hypertension
JNC
: Joint National Committee
JUPITER
: Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin
LAVi
: left atrial volume index
LIFE
: Losartan Intervention For Endpoint Reduction in Hypertensives
LV
: left ventricle/left ventricular
LVH
: left ventricular hypertrophy
LVM
: left ventricular mass
MDRD
: Modification of Diet in Renal Disease
MRFIT
: Multiple Risk Factor Intervention Trial
MRI
: magnetic resonance imaging
NORDIL
: The Nordic Diltiazem Intervention study
OC
: oral contraceptive
OD
: organ damage
ONTARGET
: ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial
PAD
: peripheral artery disease
PATHS
: Prevention And Treatment of Hypertension Study
PCI
: percutaneous coronary intervention
PPAR
: peroxisome proliferator-activated receptor
PREVEND
: Prevention of REnal and Vascular ENdstage Disease
PROFESS
: Prevention Regimen for Effectively Avoiding Secondary Strokes
PROGRESS
: Perindopril Protection Against Recurrent Stroke Study
PWV
: pulse wave velocity
QALY
: Quality adjusted life years
RAA
: renin-angiotensin-aldosterone
RAS
: renin-angiotensin system
RCT
: randomized controlled trials
RF
: risk factor
ROADMAP
: Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention
SBP
: systolic blood pressure
SCAST
: Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke
SCOPE
: Study on COgnition and Prognosis in the Elderly
SCORE
: Systematic COronary Risk Evaluation
SHEP
: Systolic Hypertension in the Elderly Program
STOP
: Swedish Trials in Old Patients with Hypertension
STOP-2
: The second Swedish Trial in Old Patients with Hypertension
SYSTCHINA
: SYSTolic Hypertension in the Elderly: Chinese trial
SYSTEUR
: SYSTolic Hypertension in Europe
TIA
: transient ischaemic attack
TOHP
: Trials Of Hypertension Prevention
TRANSCEND
: Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease
UKPDS
: United Kingdom Prospective Diabetes Study
VADT
: Veterans' Affairs Diabetes Trial
VALUE
: Valsartan Antihypertensive Long-term Use Evaluation
WHO
: World Health Organization
### 1.1 Principles
The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …
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